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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation Q12H

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 15 clinical trials

Clinical Trials


1 An Open-Label, Safety and Tolerability, Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)

This is an open-label, multi-center study designed to extend the evaluation of the safety, tolerability, and clinical effects of oral administration of KNS-760704 in patients with ALS.

NCT00931944
Conditions
  1. Amyotrophic Lateral Sclerosis
Interventions
  1. Drug: KNS-760704
MeSH:Motor Neuron Dise Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis
HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

Eligible patients will receive 1 tablet of KNS-760704 150 mg every 12 hours (Q12H) (300 mg total daily dose) for up to 180 weeks. --- Q12H ---

Primary Outcomes

Measure: The primary objective of the study is to extend the evaluation of long-term safety and tolerability of KNS-760704 300 mg daily.

Time: 180 weeks

Secondary Outcomes

Measure: The secondary objective of the study is to evaluate the long-term effects of KNS-760704 300 mg daily on measures of clinical function.

Time: 180 weeks

2 A Phase II Study Incorporating Panobinostat, Bortezomib and Liposomal Vincristine Into Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma

This is a phase-II study to evaluate the efficacy of a salvage regimen in children with relapsed T-cell ALL or lymphoma. Peg-asparaginase, mitoxantrone, intrathecal triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) and dexamethasone are commonly used drugs to treat relapsed or refractory acute lymphocytic leukemia or lymphoma (ALL). In this study, the investigators want to know if adding three drugs called panobinostat, bortezomib and liposomal vincristine (VSLI) to this regimen will result in remission (no signs or symptoms of leukemia or lymphoma). - Panobinostat has been approved by the FDA for treating adults with multiple myeloma, but it has not been approved for use in children and has not been given together with the other drugs used in this study. It has not been widely studied in children. - VSLI has been approved by the FDA for adults with relapsed or refractory ALL, but has not yet been approved for treating children with leukemia or lymphoma. - Bortezomib has been approved by the FDA for treating adults with a cancer called multiple myeloma and adults with relapsed mantle cell lymphoma; it has not been approved for treating children. PRIMARY OBJECTIVE: - To estimate the complete remission (CR) rate for patients with T-cell lymphoblastic leukemia and lymphoma in first relapse. SECONDARY OBJECTIVES: - To evaluate minimal residual disease (MRD) levels at end of each block of therapy. - To describe the toxicities of vincristine sulfate liposome injection (VSLI) when used in combination with chemotherapy and bortezomib.

NCT02518750
Conditions
  1. Acute Lymphoblastic Leukemia
  2. Lymphoma, Non-Hodgkin's
  3. Leukemia, T-Cell
  4. Leukemia, B-Cell
Interventions
  1. Drug: Dexamethasone
  2. Drug: Panobinostat
  3. Drug: Liposomal vincristine
  4. Drug: Mitoxantrone
  5. Drug: Peg-asparaginase
  6. Drug: Bortezomib
  7. Drug: Intrathecal Triples
  8. Drug: High-dose methotrexate
  9. Drug: 6-Mercaptopurine
  10. Drug: High-dose cytarabine
  11. Drug: Nelarabine
  12. Drug: Cyclophosphamide
  13. Drug: Etoposide
  14. Drug: Clofarabine
MeSH:Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Non-Hodgkin Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Leukemia, B-Cell Leukemia, T-Cell
HPO:Leukemia Lymphoid leukemia Lymphoma Non-Hodgkin lymphoma T-cell acute lymphoblastic leukemias

Additional ITs on Days 10 and 17 for patients with central nervous system (CNS) 2, 3 or traumatic tap with blasts Block B: approximately 5 weeks - High-dose methotrexate 8 g/m^2 IV over 24 hours (will not be given to patients with prior cranial irradiation) Day 1 - 6-mercaptopurine 50 mg/m^2 PO days 1-14 - ITMHA Day 1 - High-dose cytarabine 3 g/m^2 IV every 12 hours (Q12H) Days 15 and 16 Block C: approximately 3 weeks - Nelarabine 650 mg/m^2/day IV Days 1-5 (Clofarabine 40 mg/m^2/day IV Days 1-5 will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II) - Cyclophosphamide 300 mg/m^2 IV Days 1-5 - Etoposide 100 mg/m^2/day IV Days 1-5 Response evaluation is performed after the end of each treatment block. --- Q12H ---

Primary Outcomes

Description: All participants who start re-induction Block A therapy are considered evaluable. Any patient who at any time point achieves CR and goes to transplant is considered as a success; or any patient who successfully reaches the end of block C and achieves/remains in CR is considered a success; all other cases are considered as failure.

Measure: Complete Remission (CR) Rate

Time: At the end of each remission re-induction block C (approximately 13 weeks after start of therapy)

Secondary Outcomes

Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Measure: Block A Minimal Residual Disease (MRD)

Time: At the end of Block A therapy (approximately 5 weeks after start of therapy)

Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Measure: Block B Minimal Residual Disease (MRD)

Time: At the end of Block B therapy (approximately 10 weeks after start of therapy)

Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Measure: Block C Minimal Residual Disease (MRD)

Time: At the end of Block C therapy (approximately 13 weeks after start of therapy)

Description: The toxicities of liposomal vincristine (VSLI) when used in combination with chemotherapy will be evaluated. Proportions (probabilities) of relevant toxicities will be estimated with point and interval estimates.

Measure: Proportion of Relevant Toxicities

Time: At the completion of therapy (up to approximately 5 months after the start of therapy)

3 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of N91115 in Healthy Subjects

The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.

NCT02934139
Conditions
  1. Cystic Fibrosis
Interventions
  1. Drug: Cavosonstat
  2. Other: Placebo
MeSH:Cystic Fibrosis

Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily [QD] or every 12 hours [Q12H]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. --- Q12H ---

Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily [QD] or every 12 hours [Q12H]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. --- Q12H --- --- Q12H ---

Primary Outcomes

Description: Safety assessments based on clinical evaluations, laboratory assessments, and adverse events

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: 14 days

Secondary Outcomes

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in urine.

Measure: Pharmacokinetic parameters of N91115 and metabolites (Amount of analyte excreted in the urine [Ae])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in urine.

Measure: Pharmacokinetic parameters of N91115 and metabolites (% analyte excreted in the urine [Fe])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (area under the curve [AUC])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (maximum concentration [Cmax])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in urine and plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (clearance [CL])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (accumulation index [Racc])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (Terminal elimination half-life [t1/2])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (time of maximum concentration [Tmax])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (metabolite to parent exposure ratio [M/P ratio])

Time: 7 days

Description: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.

Measure: Pharmacokinetic parameters of N91115 and metabolites (terminal elimination rate constant [lambda z])

Time: 7 days

4 A Phase Ib/IIa Single Centre, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Dose Ranging Trial in Adult Participants With Uncomplicated Dengue Fever in Singapore

Dengue fever is an acute febrile illness transmitted by mosquitoes, which affects half the world's population. There are 96 million symptomatic infections, 500,0000 hospitalisations and 25,000 deaths per year attributed to the disease. The economic burden is $12 billion. In Singapore, as elsewhere, the incidence of the disease continues to increase despite aggressive control measures. At present there are no approved medicines for treating dengue fever. Only supportive fluid replacement therapy is used to treat vascular leakage in patients with severe illness. Therefore there is an urgent need to find alternative treatments. Experiments in the laboratory have shown that Celgosivir and modipafant inhibit dengue virus and improve mouse survival. Both drugs have previously been used in humans with good safety records, so investigators are taking this one step further to find out how well it works in dengue patients. Investigators plan to enroll dengue patients within 48 hours of fever onset and assign them to one of four treatment groups over five days. Together with the support from the industry partner, 60°Pharmaceuticals PLC, the investigators will determine the safety and effectiveness of these drugs on acute dengue patients and pave the way forward for dengue antiviral medicines to reach patients.

NCT02569827
Conditions
  1. Dengue Fever
Interventions
  1. Drug: Celgosivir
  2. Drug: Modipafant 50mg
  3. Drug: Placebo
  4. Drug: Modipafant 100mg
MeSH:Dengue Fever
HPO:Fever

If a signal is detected, a sample size calculation will be undertaken for Part 2. The Sponsor will convene a Scientific Advisory Board (SAB) who will then review unblinded log10 serum viral load AUC for viraemia and platelet count data to recommend which dosing monotherapy dosing regimen to advance to Part 2. If the recommended sample size for Part 2 exceeds the maximum specified for Part 1 and 2 (a total combined sample size of N = 132 participants) for a monotherapy, the Sponsor will submit a major amendment for Institutional Review Board/ Health Science Authority (IRB/HSA) consideration prior to initiating Part 2. For Part 2, up to 60 otherwise healthy participants with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be assigned in a randomised double-blind fashion to: - Cohort 5: (i) celgosivir monotherapy 150 mg Q6H, OR (ii) modipafant monotherapy (either 50 mg Q12H or 100 mg Q12H) - Cohort 6: Placebo extension for 5 days of treatment. --- Q12H ---

If a signal is detected, a sample size calculation will be undertaken for Part 2. The Sponsor will convene a Scientific Advisory Board (SAB) who will then review unblinded log10 serum viral load AUC for viraemia and platelet count data to recommend which dosing monotherapy dosing regimen to advance to Part 2. If the recommended sample size for Part 2 exceeds the maximum specified for Part 1 and 2 (a total combined sample size of N = 132 participants) for a monotherapy, the Sponsor will submit a major amendment for Institutional Review Board/ Health Science Authority (IRB/HSA) consideration prior to initiating Part 2. For Part 2, up to 60 otherwise healthy participants with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be assigned in a randomised double-blind fashion to: - Cohort 5: (i) celgosivir monotherapy 150 mg Q6H, OR (ii) modipafant monotherapy (either 50 mg Q12H or 100 mg Q12H) - Cohort 6: Placebo extension for 5 days of treatment. --- Q12H --- --- Q12H ---

Primary Outcomes

Description: Area under the curve (AUC) for serum viral load from baseline to Study Day 5 of Celgosivir dosing

Measure: Viral load AUC for viremia

Time: Day 1 to Day 5

Description: Lowest platelet count recorded from baseline to Study Day 5 of Modipafant dosing

Measure: Platelet nadir

Time: Day 1 to Day 5

Secondary Outcomes

Description: The time from the start of treatment to the start of the first 24-hour period during which the tympanic or oral temperature remains below 37.5°C

Measure: Fever clearance time (days)

Time: Day 1 to 28

Description: A 24-hour reduction in duration of illness that is treatment related is deemed clinically relevant. Draft criteria to support this include: Absence of fever (< 37.4˚C) for at least 24 hours

Measure: Duration of illness

Time: Day 1 to 28

Description: Determined by comparison of the maximum haematocrit detected in the acute phase as compared to baseline

Measure: Maximum percentage haemoconcentration

Time: Day 1 to 28

Measure: Time to NS1 clearance

Time: Day 1 to 28

5 Non-Steroidal Anti-inflammatory Drugs in Axial Spondyloarthritis: a Pilot Study

This is a 6-week randomized, double-blind trial of 4 different non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis to compare the change of pain score from baseline at 4 weeks to the change of pain score from baseline at 6 weeks.

NCT03473665
Conditions
  1. Ankylosing Spondylitis
  2. Axial Spondyloarthritis
Interventions
  1. Drug: Indomethacin
  2. Drug: Diclofenac
  3. Drug: Meloxicam
  4. Drug: Celecoxib
MeSH:Spondylitis Spondylitis, Ankylosing Spondylarthritis

Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg every 12 hours (Q12H); 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H ---

Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg every 12 hours (Q12H); 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H --- --- Q12H ---

Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg every 12 hours (Q12H); 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H --- --- Q12H --- --- Q12H ---

Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg every 12 hours (Q12H); 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H --- --- Q12H --- --- Q12H --- --- Q12H ---

Primary Outcomes

Description: Change of pain score by numerical rating score from baseline [scale range: 0 (better) -10 (worse)]

Measure: Change of Pain Score

Time: Baseline, Week 4, and Week 6

Secondary Outcomes

Description: Change of BASDAI by numerical rating score from baseline [scale range: 0 (better) -10 (worse)]

Measure: Change of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Time: Baseline, Week 4, and Week 6

Description: Change of BASFI by numerical rating score from baseline [scale range: 0 (better) -10 (worse)]

Measure: Change of Bath Ankylosing Spondylitis Function Index (BASFI)

Time: Baseline, Week 4, and Week 6

Description: Change of ASDAS by numerical rating score from baseline [scale range: 0 (better) -10 (worse)]

Measure: Change of ASAS Endorsed Disease Activity Score (ASDAS)

Time: Baseline, Week 4, and Week 6

Description: Likert Scale on whether effective or not.

Measure: Patient Global Assessment of Response to Therapy (PGART)

Time: Week 6

6 Phase 2 Clinical Trial for Comprehensive Treatment Program for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Tagraxofusp (SL-401) in Combination With HCVAD/Mini-CVD and VENETOCLAX

This phase II trial studies how well venetoclax, SL-401, and chemotherapy works in treating patients with blastic plasmacytoid dendritic cell neoplasm. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. SL-401 is a recombinant protein consisting of IL-3 linked to a toxic agent called DT. IL-3 attaches to IL-3 receptors on tumor cells in a targeted way and delivers DT to kill them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and SL-401 with chemotherapy may be an effective treatment for patients with blastic plasmacytoid dendritic cell neoplasm.

NCT04216524
Conditions
  1. Blastic Plasmacytoid Dendritic Cell Neoplasm
Interventions
  1. Drug: Cyclophosphamide
  2. Drug: Cytarabine
  3. Drug: Dexamethasone
  4. Drug: Doxorubicin
  5. Drug: Mercaptopurine
  6. Drug: Methotrexate
  7. Drug: Methylprednisolone
  8. Drug: Prednisone
  9. Biological: Rituximab
  10. Biological: Tagraxofusp-erzs
  11. Drug: Venetoclax
  12. Drug: Vincristine
MeSH:Neoplasms
HPO:Neoplasm

HYPER-CVAD (AGE < 60): Patients receive cyclophosphamide IV over 3 hours every 12 hours (Q12H) on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone orally (PO) or IV over 30 minutes on days 1-4 and 11-14, and doxorubicin IV over 24 hours on day 4. MINI-HYPER-CVD (AGE >= 60): Patients receive cyclophosphamide IV over 3 hour Q12H on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone PO or IV over 30 minutes on days 1-4 and 11-14. --- Q12H ---

HYPER-CVAD (AGE < 60): Patients receive cyclophosphamide IV over 3 hours every 12 hours (Q12H) on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone orally (PO) or IV over 30 minutes on days 1-4 and 11-14, and doxorubicin IV over 24 hours on day 4. MINI-HYPER-CVD (AGE >= 60): Patients receive cyclophosphamide IV over 3 hour Q12H on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone PO or IV over 30 minutes on days 1-4 and 11-14. --- Q12H --- --- Q12H ---

Patients may receive rituximab IV over 4-6 hours on days 1 and 8, cytarabine IT on day 5, and/or methotrexate IT on day 8. MTX/ARAC (AGE < 60): Patients receive methotrexate IV over 24 hours on day 1, and cytarabine IV over 3 hours Q12H on days 2 and 3. MINI-MTX/ARAC (AGE >= 60): Patients receive methotrexate IV over 24 hours on day 1, methylprednisolone IV over 2 hours Q12H on days 1-3, and cytarabine IV over 3 hours Q12H on days 2 and 3. ALL CYCLES: Treatment repeats every 28 days for 8 cycles in the absence of disease progression and unacceptable toxicity. --- Q12H ---

Patients may receive rituximab IV over 4-6 hours on days 1 and 8, cytarabine IT on day 5, and/or methotrexate IT on day 8. MTX/ARAC (AGE < 60): Patients receive methotrexate IV over 24 hours on day 1, and cytarabine IV over 3 hours Q12H on days 2 and 3. MINI-MTX/ARAC (AGE >= 60): Patients receive methotrexate IV over 24 hours on day 1, methylprednisolone IV over 2 hours Q12H on days 1-3, and cytarabine IV over 3 hours Q12H on days 2 and 3. ALL CYCLES: Treatment repeats every 28 days for 8 cycles in the absence of disease progression and unacceptable toxicity. --- Q12H --- --- Q12H ---

Patients may receive rituximab IV over 4-6 hours on days 1 and 8, cytarabine IT on day 5, and/or methotrexate IT on day 8. MTX/ARAC (AGE < 60): Patients receive methotrexate IV over 24 hours on day 1, and cytarabine IV over 3 hours Q12H on days 2 and 3. MINI-MTX/ARAC (AGE >= 60): Patients receive methotrexate IV over 24 hours on day 1, methylprednisolone IV over 2 hours Q12H on days 1-3, and cytarabine IV over 3 hours Q12H on days 2 and 3. ALL CYCLES: Treatment repeats every 28 days for 8 cycles in the absence of disease progression and unacceptable toxicity. --- Q12H --- --- Q12H --- --- Q12H ---

Primary Outcomes

Description: The median PFS time will be estimated by Bayesian posterior estimates. Estimated using the Kaplan-Meier method.

Measure: Progression free survival (PFS)

Time: Up to 6 years

Description: Will be reported by type, frequency and severity. Highest toxicity grades per patient per course will be tabulated for selected adverse events and laboratory measurements.

Measure: Incidence of adverse events

Time: Up to 6 years

Description: Overall response rate along with complete remission and complete remission with incomplete hematologic recovery will be estimated along with 95% confidence interval.

Measure: Overall response rate

Time: Up to 6 years

Description: The response rate will be compared between subgroups (e.g. minimal residual disease negativity, etc.) by Fisher's exact test, and Wilcoxon rank test will be used to compare the patient clinical information (e.g., protein expression) between subgroups such as response and non-response.

Measure: Rate of stem cell transplant

Time: Up to 6 years

7 An Open-Label, Randomized, Two-Period, Crossover Study to Evaluate the Effect of Oral Doses of SCY-078 (Ibrexafungerp) on the Pharmacokinetics of Dabigatran Administered Orally to Healthy Subjects

This is a Phase 1 open-label, randomized, two-period, crossover study to evaluate the effect of repeated oral doses of SCY-078 (Ibrexafungerp) on the pharmacokinetics of dabigatran administered orally to healthy subjects.

NCT04092725
Conditions
  1. Pharmacokinetics
Interventions
  1. Drug: DAB
  2. Drug: SCY-078 plus DAB

Treatment B: Twice daily (BID), every 12 hours (Q12H) oral doses of SCY-078 750mg on Day and Day 2; and single oral AM doses of SCY-078 750mg on Day 3 and Day. --- Q12H ---

Primary Outcomes

Description: AUC0-48 of DAB when taken with SCY-078

Measure: Pharmacokinetics of DAB administered with SCY-078, AUC

Time: 17 days

Secondary Outcomes

Description: Cmax DAB when taken with SCY-078.

Measure: Pharmacokinetics of DAB administered with SCY-078, Cmax

Time: 17 days

Description: Tmax of DAB when taken with SCY-078.

Measure: Pharmacokinetics of DAB administered with SCY-078, Tmax

Time: 17 days

Description: Half Life of DAB when taken with SCY-078.

Measure: Pharmacokinetics of DAB administered with SCY-078, Half Life

Time: 17 Days

Description: Incidence of treatment-related adverse events (AE) and discontinuations due to (AEs)

Measure: Safety and tolerability of oral dosing of combination of DAB with SCY-078

Time: 7 weeks

8 Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial

Patients with documented moderate COVID-19 infection will be randomized 1:1 to receive piclidenoson 2 mg Q12H orally with standard supportive care (SSC - intervention arm) or placebo orally with SSC (control arm) for up to 28 days.

NCT04333472
Conditions
  1. COVID-19
  2. Coronavirus Infection
Interventions
  1. Drug: Piclidenoson
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Severe Acute Respiratory Syndrome

Piclidenoson for Treatment of COVID-19 Patients with documented moderate COVID-19 infection will be randomized 1:1 to receive piclidenoson 2 mg Q12H orally with standard supportive care (SSC - intervention arm) or placebo orally with SSC (control arm) for up to 28 days. --- Q12H ---

Exclusion Criteria 1. Severe illness, including any of the following: - Respiratory rate >30 breaths/minute; or - SpO2 ≤93% on room air at sea level; or - Ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300; or - Lung infiltrates >50% of pulmonary volume on imaging 2. Critical illness, including any of the following: - Respiratory failure; or - Septic shock; or - Multiple organ dysfunction 3. Participation in another clinical trial concurrently 4. Concurrent treatment with immunomodulators or anti-rejection drugs 5. Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception 6. History of any of the following diseases or conditions: - Advanced or decompensated liver disease (including presence or history of bleeding varices, ascites, encephalopathy, or hepato-renal syndrome) - Inability to swallow tablets, or gastrointestinal disease which could interfere with the absorption of piclidenoson - Any malignancy within 5 years before screening; exceptions are superficial dermatologic malignancies (e.g., squamous cell or basal cell skin cancer treated with curative intent) - Cardiomyopathy, significant ischemic cardiac or cerebrovascular disease (including history of angina, myocardial infarction, or interventional procedure for coronary artery disease), or cardiac rhythm disorder - QTcF interval on an average of triplicate ECGs >450 milliseconds (msec) for males or >470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed) - Any condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, congenital Long QT Syndrome - Ongoing or planned use of a concomitant medication that is on the CredibleMeds list of drugs known to cause Torsades de Pointes unless the subject can be screened and monitored under the guidelines proposed by Giudicessi (2020) - Pancreatitis - Severe or uncontrolled psychiatric disorder, e.g., depression, manic condition, psychosis, acute and/or chronic cognitive dysfunction, suicidal behavior, and relapse of substance abuse - Active seizure disorder defined by either an untreated seizure disorder or continued seizure activity within the preceding year despite treatment with anti-seizure medication - Bone marrow or solid organ transplantation - Any serious condition that, in the opinion of the investigator, would preclude evaluation of response or make it unlikely that the contemplated course of therapy and follow-up could be completed 7. Any of the following abnormal laboratory tests: - Platelet count <90,000 cells/mm3 - Absolute neutrophil count (ANC) <1,500 cells/mm3 - Estimated creatinine clearance (CrCl) <50 mL/min by Cockroft-Gault formulation - Bilirubin level ≥2.5 mg/dL unless due to Gilbert's syndrome - AST or ALT level ≥3X the upper limit of normal - Serum albumin level <3.0 g/dL - International normalized ratio (INR) ≥1.5 (except subjects maintained on anticoagulant medications) COVID-19 Coronavirus Infection Coronavirus Infections Severe Acute Severe Acute Respiratory Syndrome This is a randomized, double-blind, placebo-controlled, pilot trial of piclidenoson 2 mg Q12H added to SSC, compared to placebo plus SSC, in a population of hospitalized subjects with "Moderate" COVID-19 per U.S. National Institutes of Health (NIH) Coronavirus Disease 2019 (COVID-19) Treatment Guidelines (2020). --- Q12H ---

Primary Outcomes

Description: Proportion of subjects alive and free of respiratory failure (defined as need for non-invasive or invasive mechanical ventilation, high-flow oxygen, or extracorporeal membrane oxygenation) at Day 29

Measure: Proportion of subjects alive and free of respiratory failure

Time: 29 days

Description: Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29

Measure: Proportion of subjects discharged home alive

Time: 29 days

Description: Proportion of patients experiencing AEs

Measure: Treatment-emergent adverse events (AEs)

Time: 29 days

Secondary Outcomes

Description: • Clinical status at Day 29 on NIAID 8-point ordinal scale (NIH 2020): Not hospitalized, no limitations Not hospitalized, with limitations Hospitalized, no active medical problems Hospitalized, not on oxygen Hospitalized, on oxygen Hospitalized, on high-flow oxygen or noninvasive mechanical ventilation Hospitalized, on mechanical ventilation or ECMO Death

Measure: Clinical status

Time: 29 days

Description: Time (days) to improvement of 2 points on 7-point ordinal clinical scale

Measure: Time to improvement

Time: 29 days

Description: Proportion of patients who require mechanical ventilation

Measure: Incidence of mechanical ventilation

Time: 29 days

Description: Ventilator-free days to Day 29

Measure: Ventilator-free days

Time: 29 days

Description: Proportion of patients who require ICU admission

Measure: Incidence of Intensive Care Unit (ICU) admission

Time: 29 days

Description: Duration (days) of ICU stay

Measure: Duration of ICU stay

Time: 29 days

Description: Time (days) to hospital discharge

Measure: Time to hospital discharge

Time: 29 days

Description: Duration (days) of need for supplemental oxygen

Measure: Duration of need for supplemental oxygen

Time: 29 days

Description: Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling

Measure: Time to virus negativity

Time: 29 days

Description: SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR

Measure: SARS-CoV-2 viral load

Time: 29 days

Description: Proportion of patients experiencing AEs leading to early discontinuation of trial treatment

Measure: AEs leading to withdrawal

Time: 29 days

Description: Proportion of patients experiencing SAEs

Measure: Treatment-emergent serious AEs (SAEs)

Time: 29 days

Description: Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs

Measure: Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)

Time: 29 days

Description: Proportion of patients who meet study safety-related stopping rules

Measure: Incidence of meeting safety-related stopping rules

Time: 29 days

Description: Plasma concentrations over time of piclidenoson

Measure: Pharmacokinetics of piclidenoson in this patient population

Time: 5 days

Description: Change from baseline in serum concentrations of cytokines

Measure: Serum cytokine levels

Time: 29 days

9 A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38 MAPK Inhibitor, Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin for Women With Platinum-Sensitive Ovarian Cancer

A study for women with ovarian cancer that has returned at least 6 months after platinum-based chemotherapy.

NCT01663857
Conditions
  1. Epithelial Ovarian Cancer
  2. Fallopian Tube Cancer
  3. Primary Peritoneal Cancer
Interventions
  1. Drug: LY2228820
  2. Drug: Carboplatin
  3. Drug: Placebo
  4. Drug: Gemcitabine
MeSH:Ovarian Neoplasms Carcinoma, Ovarian Epithelial Fallopian Tube Neoplasms
HPO:Fallopian tube carcinoma Ovarian neoplasm

The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).. Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin. --- Q12H ---

Primary Outcomes

Description: Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).

Measure: Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])

Time: Cycle 1 (21 Days)

Description: PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Measure: Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin

Time: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

Secondary Outcomes

Description: Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Measure: Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)

Time: Baseline to Disease Progression (up to 3 years)

Description: Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.

Measure: Phase 2: Overall Survival

Time: Baseline to Date of Death from any cause (up to 5 years)

Description: PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.

Measure: Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820

Time: Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD

Description: The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.

Measure: Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score

Time: Baseline, Study Completion (up to 3 years)

10 A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Multiple Escalating Oral Doses Of Pf-06427878 Co Administered With And Without Food In Healthy Adult Subjects

PF-06427878 is a new compound proposed for the treatment of hyperlipidemia. The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple oral doses of PF-06427878 in healthy adult subjects.

NCT02391623
Conditions
  1. Healthy Subjects
Interventions
  1. Drug: PF-06427878
  2. Drug: Placebo
  3. Drug: PF-06427878
  4. Drug: Placebo

Maximum Observed Plasma Concentration (Cmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1. null. --- Q12H ---

Maximum Observed Plasma Concentration (Cmax) for PF-06427878during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12. null. --- Q12H ---

Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1. null. --- Q12H ---

Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12. null. --- Q12H ---

Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1. null. --- Q12H ---

Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12. null. --- Q12H ---

Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Plasma Decay Half-Life (t1/2) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Apparent Volume of Distribution (Vz/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Apparent Oral Clearance (CL/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Minimum Observed Plasma Concentration (Cmin) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Peak:Trough ratio of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD. --- Q12H ---

Amount of PF-06427878 excreted in urine (Ae) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Percent of dose excreted in urine as PF-06427878 (Ae%) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Renal clearance of PF-06427878 (CLr) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---

Primary Outcomes

Measure: Assessment of adverse events (AEs).

Time: 0-25 days

Measure: Assessment of clinical laboratory tests.

Time: 0-25 days

Measure: Assessment of vital signs (including blood pressure and pulse rate).

Time: 0-25 days

Measure: Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG).

Time: 0-25 days

Secondary Outcomes

Measure: Maximum Observed Plasma Concentration (Cmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Maximum Observed Plasma Concentration (Cmax) for PF-06427878during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Maximum Observed Plasma Concentration (Cmax) for PF-06427878 on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12 hours post dose

Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Plasma Decay Half-Life (t1/2) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Apparent Volume of Distribution (Vz/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Apparent Oral Clearance (CL/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Minimum Observed Plasma Concentration (Cmin) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Peak:Trough ratio of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1

Time: 0, 1, 2, 3, 4, 6, 8, 12 hours post dose

Measure: Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUCtau)) for PF-06427878 on day14 relative to day 1

Time: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose

Measure: Amount of PF-06427878 excreted in urine (Ae) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0- tau hours post dose

Measure: Percent of dose excreted in urine as PF-06427878 (Ae%) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0- tau hours post dose

Measure: Renal clearance of PF-06427878 (CLr) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14

Time: 0- tau hours post dose

11 A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations

This phase III trial compares standard chemotherapy to therapy with CPX-351 and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.

NCT04293562
Conditions
  1. Acute Myeloid Leukemia
Interventions
  1. Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  2. Drug: Asparaginase
  3. Drug: Asparaginase Erwinia chrysanthemi
  4. Behavioral: Cogstate Assessment Battery
  5. Drug: Cytarabine
  6. Drug: Daunorubicin Hydrochloride
  7. Drug: Dexrazoxane Hydrochloride
  8. Drug: Etoposide
  9. Drug: Gemtuzumab Ozogamicin
  10. Drug: Gilteritinib Fumarate
  11. Drug: Liposome-encapsulated Daunorubicin-Cytarabine
  12. Drug: Methotrexate
  13. Drug: Mitoxantrone Hydrochloride
  14. Drug: Therapeutic Hydrocortisone

TREATMENT FOR PATIENTS WITHOUT FLT3 MUTATIONS: ARM A LOW RISK GROUP 1: INDUCTION 1: Patients receive cytarabine intravenously (IV) over 1-30 minutes every 12 hours (Q12H) on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H ---

Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5. INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5. --- Q12H ---

Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5. INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5. --- Q12H --- --- Q12H ---

INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi intramuscularly (IM) or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. ARM B LOW RISK GROUP 1: INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H ---

Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5. INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5. --- Q12H ---

INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. ARM A LOW RISK GROUP 2: INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H ---

INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. ARM A LOW RISK GROUP 2: INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H --- --- Q12H ---

INTENSIFICATION 2: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4 and dexrazoxane IV over 5-15 minutes and mitoxantrone hydrochloride (mitoxantrone) IV over 5-15 minutes on days 3-6. --- Q12H ---

INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. ARM B LOW RISK GROUP 2: INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H ---

INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. ARM A HIGH RISK GROUP: INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H ---

INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. ARM A HIGH RISK GROUP: INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. --- Q12H --- --- Q12H ---

TREATMENT FOR PATIENTS WITH FLT3/ITD MUTATIONS (ITD AR > 0.1): ARM AC LOW RISK GROUP 2: CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. --- Q12H ---

Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38. --- Q12H ---

INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33. --- Q12H ---

INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34. --- Q12H ---

INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37. --- Q12H ---

ARM AC HIGH RISK GROUP: CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. --- Q12H ---

TREATMENT FOR NON-ITD FLT3 ACTIVATING MUTATIONS: ARM AD LOW RISK GROUP 2: CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. --- Q12H ---

ARM AD HIGH RISK GROUP: CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. --- Q12H ---

Primary Outcomes

Description: The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.

Measure: Event-free survival (EFS)

Time: Up to 3 years

Secondary Outcomes

Description: The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.

Measure: Overall survival (OS)

Time: Up to 3 years

Description: The proportion of patients MRD+ at end of induction 1 (EOI1) will be estimated as the number of patients MRD+ divided by the number of patients with evaluable EOI1 MRD results along with a corresponding 95% confidence interval determined using a binomial exact method.

Measure: Proportion of patients positive for minimal residual disease (MRD+)

Time: Up to 4 weeks

Description: The proportion of patients who died during protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method.

Measure: Proportion of patients who died during protocol therapy

Time: Up to 2 years

Description: Cumulative incidence estimates will be used to determine the 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events.

Measure: Relapse rate

Time: Up to 3 years

Description: Cumulative incidence estimates will be used to determine the 3 year TRM defined as time from study entry to death where induction failure, relapse or secondary malignancies are competing events.

Measure: Treatment-related mortality rate (TRM)

Time: Up to 3 years

Description: The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

Measure: Incidence of adverse events

Time: Up to 2 years

Other Outcomes

Description: Median and range of the length of course duration will be determined.

Measure: Course duration

Time: Up to 2 years

Description: Median and range of the length of hospitalization time during protocol therapy will be determined.

Measure: Length of hospitalization

Time: Up to 2 years

Description: Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery in days where deaths are competing events.

Measure: Time to count recovery

Time: Up to 2 years

12 A Phase II Open Label Randomised Controlled Clinical Trial of Different Dosing Regimens of Fludrocortisone in Septic Shock With Assessment of Temporal Changes in Hormonal, Inflammatory, and Genetic Markers of Vascular Responsiveness

The purpose of this study is to determine the most suitable dose of Fludrocortisone in reversal of sepsis and shock associated with sepsis in patients who are admitted to the ICU. The investigators will be looking to see whether patients receiving Fludrocortisone at different doses recover quicker and spend less time in hospital and in ICU, and to understand the reasons why this happens at certain doses. Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the bloodstream from a site of infection. In some people, the infection can progress to sepsis and septic shock where the functions of organs in the body are affected. Patients suffering from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they are prescribed antibiotics as standard therapy, as well as other therapies to support the functions of the body. Fludrocortisone is a steroid that has previously shown to be beneficial to help in shock in patients in ICU, but more information is required about the exact dose that is required to achieve this. This has been shown by previous research. However, the exact role of Fludrocortisone and the best dose has not been studied adequately to date as well as the ways in how it works within the body. The study aims to look tat the dose and the way it works.

NCT04494789
Conditions
  1. Critically Ill
  2. Septic Shock
Interventions
  1. Drug: Fludrocortisone Acetate
  2. Drug: Fludrocortisone Acetate
  3. Drug: Fludrocortisone Acetate
  4. Other: Standard Therapy
MeSH:Shock, Septic Shock Critical Illness

300 patients will be recruited and randomised to enteral doses of 50mcg fludrocortisone Q24H, Q12H, Q6H or to the control arm of the study. --- Q24H --- --- Q12H ---

Primary Outcomes

Description: To the assess the time it takes for shock to resolve in each intervention arm

Measure: Time to resolution of shock by Intervention group allocation

Time: 7 DAYS

Description: Assess the levels of fludrocortisone in the interventional groups at time of resolution of shock

Measure: Time to resolution of shock and Fludrocortisone Levels

Time: 7 days

Description: Area under the curve of vasopressor dose in each intervention arm

Measure: Vasopressor Responsiveness by Intervention group allocation

Time: 7 days

Description: Area under the curve of vasopressor dose associated with fludrocortisone levels

Measure: Vasopressor Responsiveness and Fludrocortisone Levels

Time: 7 days

Secondary Outcomes

Description: Time between a new episode of shock after reversal of the initial episode

Measure: Recurrence of shock

Time: censored at day 28

Description: Number of Days that are without ventilation during admission

Measure: Ventilation free days

Time: censored at day 28

Description: Total number of days in ICU and in hospital for the index admission

Measure: ICU and hospital length of Stay

Time: censored at day 28

Description: The number of deaths that are recorded in participants and the location of the deaths when in hospital - ICU or ward. This will include cause of death

Measure: ICU and hospital mortality

Time: censored at day 28

Description: Baseline SOFA score to SOFAmax - numerical calculation based on scoring system of each participant during their admission

Measure: Delta SOFA Score

Time: censored at day 28

Description: Maximum SOFA score for each participant during their admission

Measure: Maximal SOFA score

Time: censored at day 28

Description: This is the number of new infections that occur >48hrs after commencing study drug

Measure: Superinfection

Time: censored at day 28

Other Outcomes

Description: Time to peak concentration of Fludrocortisone

Measure: Pharmacokinetic Outcome To assess the plasma levels of enterally administered fludrocortisone in all patients enrolled

Time: 7 days

Description: Time to absorption, clearance and metabolism of fludrocortisone in participants in each intervention arm except for the control arm

Measure: Pharmacokinetic Outcomes - To undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled (10 patients in each dosing group)

Time: 7 days

Description: Acquisition of blood samples at 4 timepoints over the first 7 days or until discharge from ICU for exploratory analysis to assess a range of biomarkers and their interactions with the primary outcomes

Measure: Vascular Responsiveness Analysis

Time: 7 days

13 Comparison of Oral Thiazides vs Intravenous Thiazides vs Tolvaptan in Combination With Loop Diuretics for Diuretic Resistant Decompensated Heart Failure

Broad Objectives: To determine the comparative efficacy of commonly employed strategies to overcome loop diuretic resistance when added to concomitant loop diuretics in hospitalized decompensated heart failure patients with hypervolemia Specific Aims: 1. Compare the 48-hour weight change of either intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in decompensated heart failure 2. Compare the adverse effects of electrolyte depletion and renal function changes between intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure 3. Pharmacoeconomic analysis of the direct costs of intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure The investigators will conduct a dual center, randomized, double-blind, double-dummy, parallel design trial comparing: oral metolazone, intravenous chlorothiazide, or oral tolvaptan, in combination with loop diuretics in 60 patients hospitalized for hypervolemic decompensated heart failure and displaying loop diuretic resistance.

NCT02606253
Conditions
  1. Heart Failure
Interventions
  1. Drug: tolvaptan
  2. Drug: Chlorothiazide
  3. Drug: Metolazone
MeSH:Heart Failure
HPO:Abnormal left ventricular function Congestive heart failure Right ventricular failure

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H ---

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H ---

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H ---

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H --- --- Q12H ---

Primary Outcomes

Description: The primary outcome will be 48-hour standing scale weight change (kg) from enrollment among the metolazone, intravenous chlorothiazide, and tolvaptan arms, using metolazone group as the comparator group for all other groups.

Measure: Weight Change Over 48 Hours

Time: 48 hours

Secondary Outcomes

Description: Net urine output from enrollment to the end of study at 48 hours measured in liters

Measure: Net Urine Output

Time: 48 hours

Description: Mean change in serum creatinine (mg/dl) from enrollment to end of study at 48 hours

Measure: Mean Change in Serum Creatinine

Time: 48 hours

Description: Mean change in glomerular filtration rate from enrollment to end of study at hospital discharge, an average of 5 days

Measure: Mean Change in Glomerular Filtration Rate at Discharge

Time: hospital discharge an average of 5 days

Description: Mean change in serum potassium (mEq/L) from enrollment to end of study at 48 hours

Measure: Mean Change in Serum Potassium

Time: 48 hours

Description: Cumulative dose of potassium supplementation (mEq) administered from enrollment to end of study at 48 hours

Measure: Potassium Supplementation

Time: 48 hours

Description: Incidence of hypokalemia (serum potassium less than 3.5mEq/L ) from enrollment to end of study

Measure: Number of Patients With Hypokalemia

Time: 48 hours

Description: Provider escalation of loop diuretic dosage at 24 hours for urine output less than 3 L at 24 hours

Measure: Number of Patients With Escalation of Loop Diuretic Therapy

Time: 24 hours

Description: Incidence of new atrial or ventricular arrhythmias from enrollment to end of study at 48 hours

Measure: Number of Patients With Cardiac Arrhythmias

Time: 48 hours

Description: SBP < 85 mmHg plus medical intervention for symptomatic hypotension

Measure: Number of Patients With Symptomatic Hypotension

Time: 48 hours

Description: Change in estimated glomerular filtration rate (ml/min/m2) from baseline to 48 hours

Measure: Change in eGFR From Baseline to 48 Hours

Time: 48 hours

Description: Mean change in serum sodium (mEq/L) from enrollment to end of study at 48 hours

Measure: Mean Change in Serum Sodium

Time: 48 hours

Other Outcomes

Description: Incidence of death from study enrollment to hospital discharge, an average of 5 days

Measure: Number of Patients With In-hospital Mortality

Time: Enrollment to hospital discharge an average of 5 days

Description: Incidence of new initiation of dopamine, dobutamine, or milrinone from enrollment to end of study at 48 hours

Measure: Number of Patients With New Inotrope Utilization

Time: 48 hours

Description: Incidence of Renal replacement therapy utilization (hemodialysis, ultrafiltration) from enrollment to hospital discharge, an average of 5 days

Measure: Number of Patients With Renal Replacement Therapy Utilization

Time: enrollment to hospital discharge an average of 5 days

Description: Diuretic Efficiency is calculated as 48hr urine output/ 48hr Furosemide equivalents in milligrams

Measure: Diuretic Efficiency

Time: 48 hours

Description: Change in serum chloride (mEq/L) from baseline to 48 hrs

Measure: Change in Serum Chloride From Baseline

Time: 48 hours

Description: Participants will score their congestion on a 10cm scale ranging from "Best" (10cm) to "Worst" (0cm). Change in score (units in centimeters) from baseline to 48 hours.

Measure: Change in Patient Congestion Score

Time: 48 hours

14 Randomized, Open Label, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-663068 in HIV-1 Infected Subjects

Research Hypothesis: Administration of BMS-663068, a prodrug for HIV attachment inhibitor BMS-626529, will result in a mean decrease of at least 1 log10 in HIV RNA at Day 9 following 8 days of therapy in at least one dosing regimen that is safe and well tolerated in Clade B HIV-1 infected subjects.

NCT01009814
Conditions
  1. HIV Infections
Interventions
  1. Drug: BMS-663068
  2. Drug: Ritonavir
MeSH:HIV Infections

Number of participants with any clinically significant abnormalities in laboratory parameters have been presented.. Maximum Observed Plasma Concentration (Cmax) of BMS-626529 Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess Cmax of BMS-626529 following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 evening dose (PM) and Day 8 morning (AM) + evening dose (PM).. Trough Observed Plasma Concentration (Ctrough) of BMS-626529 Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to access Ctrough of BMS-626529 following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8 and Day 8 evening dose (PM).. Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-626529 Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess AUC (tau) of BMS-626529 following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 1 and Day 8 evening dose (PM).. Area Under the Concentration-time Curve Over a 24-hour Period (AUC [0-24]) of BMS-626529 Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess AUC (0-24) of BMS-626529 following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 8.. Accumulation Index (AI) of BMS-626529 Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess Accumulation Index of BMS-626529 following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 8 evening dose (PM).. Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following Q12H Dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented.. Inhibitory Quotient of BMS-626529 by Ctrough Following Q12H Dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented.. Cmax of Ritonavir Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess Cmax of ritonavir following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 evening dose (PM) and Day 8 morning (AM) + evening dose (PM).. Ctrough of Ritonavir Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to access Ctrough of ritonavir following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8 and Day 8 evening dose (PM).. AUC (Tau) of Ritonavir Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess AUC (tau) of ritonavir following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 1 and Day 8 evening dose (PM).. AUC (0-24) of Ritonavir Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess AUC (0-24) of ritonavir following Q12H dosing. --- Q12H ---

Geometric mean and geometric coefficient of variation are presented for Day 8.. Accumulation Index of Ritonavir Following Q12H Dosing. --- Q12H ---

Blood samples were collected at indicated time points to assess Accumulation Index of ritonavir following Q12H dosing. --- Q12H ---

Primary Outcomes

Description: The primary assessment of the antiviral activity of BMS-663068 was assessed on the log10 change from Baseline in HIV RNA to Day 9. Baseline was the last non-missing observation before first dose (Day 1 pre-dose) and change from Baseline was calculated by subtracting Baseline value from post-Baseline visit value. An analysis of covariance (ANCOVA) model correcting for Baseline HIV viral load and treatment group was used to test the differences in mean log10 decrease in HIV RNA at Day 9 between 2 regimen groups by antiretroviral treatment history (ARV [antiretroviral] naive, ARV experienced, and combined [ARV naive + ARV experienced]). For the combined group (ARV naive +ARV experienced) an additional ANCOVA was used correcting also for treatment history as an additional covariate. Only Clade B participants were included in the population.

Measure: Mean Logarithm With Base 10 (Log10) Change From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Day 9

Time: Baseline and Day 9

Secondary Outcomes

Description: Blood samples were collected for evaluation of CD4+ and CD8+ cells at Baseline (Day 1, pre-dose), Day 8, Day 15 (Follow up) and Day 50 (study discharge). Baseline was the last non-missing observation before first dose (Day 1 pre-dose) and change from Baseline was calculated by subtracting Baseline value from post-Baseline visit value.

Measure: Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count and Cluster of Differentiation 8 Positive (CD8+) Cell Count

Time: Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50

Description: Blood samples were collected for evaluation of percent CD4+ and percent CD8+ cells at Baseline (Day 1, pre-dose), Day 8, Day 15 (Follow up) and Day 50 (study discharge). Baseline was the last non-missing observation before first dose (Day 1 pre-dose) and change from Baseline was calculated by subtracting Baseline visit value from post-Baseline visit value.

Measure: Change From Baseline in Percent CD4+ Cell Count and Percent CD8+ Cell Count

Time: Baseline (Day 1 pre-dose), Day 8, Day 15 and Day 50

Description: An AE is any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Any untoward medical occurrence resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent serious outcomes were categorized as SAE. Treatment emergent adverse events (occurred after start of treatment) have been presented.Safety Population comprised of all randomized participants who used the trial medication at least once.

Measure: Number of Participants With Treatment Emergent Non-serious Adverse Event (Non-SAE) and Serious AE (SAE)

Time: Up to 50 days

Description: A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Any abnormality found by investigator during physical examination were recorded. Number of participants with any abnormality in physical examination during study have been reported.

Measure: Number of Participants With Any Abnormality in Physical Examination

Time: Up to 50 days

Description: Vital signs including DBP and SBP were recorded. Normal ranges were as following: For DBP, lower limit: value <55 millimeter of mercury (mmHg) and change <-20 mmHg; upper limit: value >90 mmHg and change >20 mmHg). For SBP, lower limit: value <90 mmHg and change <-10 mmHg; upper limit: value >140 mmHg and change >10 mmHg. Number of participants with worst-case abnormalities are presented. Worst-case abnormality was defined as: (1) Below Normal: at least one post-Baseline assessment was below normal range, and no post-Baseline assessment was above normal range. (2) Above Normal: at least one post-Baseline assessment was above normal range, and no post-Baseline assessment was below normal range. (3) Within Normal: all post-Baseline assessments were within normal range. It was to be considered as 'Missing' when there were no post-Baseline assessments.

Measure: Number of Participants With Worst-case Abnormalities in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Time: Up to 50 days

Description: Vital signs (body temperature, RR, and HR) were recorded. Normal range were: For HR, lower limit: 55 beats per minute (bpm) and change <-15 bpm; upper limit: >100 bpm and change >30 bpm). For temperature, lower limit: 36.0 Celsius; upper limit: >37.5 Celsius or change >1.7 Celsius). For RR, lower limit: 8 breaths per minute; upper limit: >16 breaths per minute or change >10 breaths per minute. Number of participants with worst-case abnormalities are presented. Worst-case abnormality was defined as: (1) Below Normal: at least one post-Baseline assessment was below normal range, and no post-Baseline assessment was above normal range. (2) Above Normal: at least one post-Baseline assessment was above normal range, and no post-Baseline assessment was below normal range. (3) Within Normal: all post-Baseline assessments were within normal range. It was to be considered as 'Missing' when there were no post-Baseline assessments.

Measure: Number of Participants With Worst-case Abnormalities in Body Temperature, Respiratory Rate [RR], and Heart Rate [HR]

Time: Up to 50 days

Description: A 12-lead ECG was recorded during the study using an ECG machine that automatically measures ECG parameters. Normal range for ECG parameters were: PR interval (upper: 200 milliseconds [ms]); QRS (lower: 50 ms; upper: 120 ms); Corrected QT interval by Bazett formula (QTcB) (change from Baseline - increases by > 30 ms); Corrected QT interval by Fredericia formula (QTcF) (change from Baseline - increases by > 30 ms). Number of participants with worst-case abnormalities are presented which was defined as: (1) Below Normal: at least one post-Baseline assessment was below normal range, and no post-Baseline assessment was above normal range. (2) Above Normal: at least one post-Baseline assessment was above normal range, and no post-Baseline assessment was below normal range. Within Normal: all post-Baseline assessments were within normal range. It was to be considered as 'Missing' when there were no post-Baseline assessments.

Measure: Number of Participants With Worst-case Abnormalities in Electrocardiogram (ECG) Parameters

Time: Up to 50 days

Description: Laboratory parameters included hematology, clinical chemistry and urine parameters. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Any abnormal laboratory test results which were considered clinically significant by the investigator were recorded on the case report form. Number of participants with any clinically significant abnormalities in laboratory parameters have been presented.

Measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

Time: Up to 50 days

Description: Blood samples were collected at indicated time points to assess Cmax of BMS-626529 following Q12H dosing. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (Anti Meridiem [AM]), Day 8 evening dose (Post Meridiem [PM]) and Day 8 morning + evening dose (AM+PM). Pharmacokinetic parameter values were derived by non-compartmental methods. Pharmacokinetic (PK) Population was used which comprised of all participants who receive BMS-663068 and provided pharmacokinetic samples.

Measure: Maximum Observed Plasma Concentration (Cmax) of BMS-626529 Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess Cmax of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 evening dose (PM) and Day 8 morning (AM) + evening dose (PM).

Measure: Cmax of BMS-626529 Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to access Ctrough of BMS-626529 following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8, Day 8 morning dose (AM) and Day 8 evening dose (PM).

Measure: Trough Observed Plasma Concentration (Ctrough) of BMS-626529 Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Days 5,6,7: pre-morning dose

Description: Blood samples were collected at indicated time points to assess Ctrough of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8 and Day 8 evening dose (PM).

Measure: Ctrough of BMS-626529 Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose

Description: Blood samples were collected at indicated time points to assess AUC (tau) of BMS-626529 following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (AM) and Day 8 evening dose (PM).

Measure: Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-626529 Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess AUC (tau) of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1 and Day 8 evening dose (PM).

Measure: AUC (Tau) of BMS-626529 Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to assess AUC (0-24) of BMS-626529 following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

Measure: Area Under the Concentration-time Curve Over a 24-hour Period (AUC [0-24]) of BMS-626529 Following Q12H Dosing

Time: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess AUC (0-24) of BMS-626529 following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

Measure: AUC (0-24) of BMS-626529 Following QHS Dosing

Time: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to assess Accumulation Index of BMS-626529 following Q12H dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 morning dose (AM).

Measure: Accumulation Index (AI) of BMS-626529 Following Q12H Dosing

Time: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess Accumulation Index of BMS-626529 following QHS dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 evening dose (PM).

Measure: Accumulation Index of BMS-626529 Following QHS Dosing

Time: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measures were used in evaluating IQ: Cmin and Css,avg. Geometric mean and geometric coefficient of variation are presented.

Measure: Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Day 9: pre-dose, 4,12 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-morning dose

Description: Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measures were used in evaluating IQ: Cmin and Css,avg. Geometric mean and geometric coefficient of variation are presented.

Measure: Inhibitory Quotient (IQ) of BMS-626529 by Css,Avg and by Lowest Concentration of a Drug During Dosing Interval (Cmin) Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Day 2: pre-evening dose, 12,16 hours; Day 9: pre-dose, 12,16 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-evening dose

Description: Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measure was used in evaluating IQ: Ctrough. Geometric mean and geometric coefficient of variation are presented.

Measure: Inhibitory Quotient of BMS-626529 by Ctrough Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Day 9: pre-dose, 4,12 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-morning dose

Description: Blood samples were collected at indicated time points to assess IQ of BMS-626529. Inhibitory quotient was calculated as the ratio of BMS-626529 in vivo exposure to in vitro measured protein binding adjusted EC90 (PBA-EC90). The following in vivo exposure measure was used in evaluating IQ: Ctrough. Geometric mean and geometric coefficient of variation are presented.

Measure: Inhibitory Quotient of BMS-626529 by Ctrough Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 2: pre-evening dose, 12,16 hours; Day 9: pre-dose, 12,16 hours; Day 10: pre-dose, 12 hours; Day 11: pre-dose; Days 5,6,7: pre-evening dose

Description: Blood samples were collected at indicated time points to assess Cmax of ritonavir following Q12H dosing. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (AM), Day 8 evening dose (PM) and Day 8 morning + evening dose (AM+PM). Pharmacokinetic parameter values were derived by non-compartmental methods. PK Population was used which comprised of all participants who receive ritonavir and provided pharmacokinetic samples.

Measure: Cmax of Ritonavir Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess Cmax of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 evening dose (PM) and Day 8 morning (AM) + evening dose (PM).

Measure: Cmax of Ritonavir Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to access Ctrough of ritonavir following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8, Day 8 morning dose (AM) and Day 8 evening dose (PM).

Measure: Ctrough of Ritonavir Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours; Days 5,6,7: pre-morning dose

Description: Blood samples were collected at indicated time points to assess Ctrough of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Days 5, 6, 7, 8 and Day 8 evening dose (PM).

Measure: Ctrough of Ritonavir Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours; Days 5,6,7: pre-evening dose

Description: Blood samples were collected at indicated time points to assess AUC (tau) of ritonavir following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1, Day 8 morning dose (AM) and Day 8 evening dose (PM).

Measure: AUC (Tau) of Ritonavir Following Q12H Dosing

Time: Days 1, 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess AUC (tau) of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 1 and Day 8 evening dose (PM).

Measure: AUC (Tau) of Ritonavir Following QHS Dosing

Time: Days 1, 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to assess AUC (0-24) of ritonavir following Q12H dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

Measure: AUC (0-24) of Ritonavir Following Q12H Dosing

Time: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12, 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess AUC (0-24) of ritonavir following QHS dosing. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8.

Measure: AUC (0-24) of Ritonavir Following QHS Dosing

Time: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

Description: Blood samples were collected at indicated time points to assess Accumulation Index of ritonavir following Q12H dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 morning dose (AM).

Measure: Accumulation Index of Ritonavir Following Q12H Dosing

Time: Day 8: pre-morning dose, 1,2,3,4,5,6,8,12 hours; Day 8: 13,14,15,16,17,18,20 hours

Description: Blood samples were collected at indicated time points to assess Accumulation Index of ritonavir following QHS dosing. AI was calculated as ratio of AUC(tau) at steady-state to AUC(tau) after the first dose. Pharmacokinetic parameter values were derived by non-compartmental methods. Geometric mean and geometric coefficient of variation are presented for Day 8 evening dose (PM).

Measure: Accumulation Index of Ritonavir Following QHS Dosing

Time: Day 8: pre-evening dose, 1,2,3,4,5,6,8 hours

15 An Interventional, Open Label, and Randomized Controlled Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Opioid-naive Patients With Moderate to Severe Cancer Pain

This study is to evaluate the efficacy and safety of a titration method by selects 10 mg control-released (CR) oxycodone tablet as background drug in combined with immediate-released (IR) oxycodone, compared to conventional titration method with immediate-released (IR) oxycodone in patients with moderate to severe cancer pain in Taiwan.

NCT03176199
Conditions
  1. Cancer
  2. Pain
Interventions
  1. Drug: Oxycodone
  2. Drug: Oxycodone
MeSH:Cancer Pain

Meanwhile, the titration with IR oxycodone will be added according to the pain intensity, e.g. if patient receiving 6 tablets of 10 mg CR oxycodone (giving in Q12H frequency for 3 days), 12 capsules of 5mg IR oxycodone will be dispensed for managing acute pain (rescue use) for the first cycle. --- Q12H ---

Primary Outcomes

Description: The change from baseline of NRS pain score and the daily number of breakthrough pain

Measure: To evaluate the variable change of NRS pain score and the number of breakthrough pain to obtain pain control after treatment

Time: Up to 14 days

Secondary Outcomes

Description: The percentage of patients in each titration cycle

Measure: To evaluate the percentage of patients in each titration cycle

Time: Up to 14 days

Description: The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control

Measure: To evaluate the number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control

Time: Up to 14 days

Description: The total opioid taken within 24 hrs daily from baseline to day 14

Measure: The total opioid taken within 24hrs daily from baseline to day 14

Time: Up to 14 days

Description: Mean daily NRS score of patients from baseline to day 14

Measure: To evaluate the mean daily NRS score of subjects from baseline to day 14

Time: Up to 14 days

Description: The total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14

Measure: To evaluate the total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14

Time: Up to 14 days

Description: The occurrence rate of adverse events and physical examination status

Measure: To evaluate the tolerability and safety of Oxycodone CR and IR in cancer pain patient

Time: Up to 28 days

Description: The change from baseline in questionnaire

Measure: To evaluate the change from baseline in questionnaire

Time: Up to 14 days


HPO Nodes


HP:0001635: Congestive heart failure
Genes 264
TLL1 DSP PLN SLC25A26 BSCL2 DSP NDUFB11 ACTC1 RET TRNL1 JUP CAV1 TRNK SGCD ACTC1 KCNJ5 GTF2IRD1 TRNC FXN WRN HBA2 TTN CAVIN1 VHL ATP6V1A PPA2 FGFR3 MYH7 TRNS2 EYA4 PLOD1 LMNA BMP2 KIF1B SLC2A10 NDUFB8 GNA11 CACNA1S ND1 HADHA TCF4 GAA TRNK VCL GATA6 TBL2 MYL3 PLOD1 ABCC6 GNPTAB SDHD STRADA PNPLA2 ENG LMNA CLIP2 RFC2 TAZ TPI1 COL1A2 BAG3 LIMK1 DSP GTPBP3 DES IRF5 NDUFAF1 ELN SELENON PSMB8 HJV MYD88 MYH6 AGGF1 EYA4 ATP5F1A TET2 ND6 HFE DMD MST1 MAPRE2 DLST DNMT3A TNNI3K TUBB TNNT2 EFEMP2 TRIP4 DNAJC19 XYLT1 TRNQ SDHB GDNF ADCY5 EPAS1 GDF2 PRKAG2 PSEN2 CCR6 AFF4 COL1A1 CDH23 CITED2 ENPP1 RAB3GAP2 BCHE FLNC GLA SF3B1 TRNW HADHA DES IFIH1 MECP2 TMEM70 GATAD1 ACAD9 HBB ACVRL1 HADHB MTTP RASA1 TMEM127 FGF23 NF1 PRDM16 SDHAF2 PRKAR1A FGD1 LMNA NDUFAF3 TNNI3 RBM20 VHL IKBKG VPS33A XYLT2 MYH6 SDHD TRPM4 GLB1 ALMS1 SDHD COX1 TPM1 AGPAT2 SCN5A CLIC2 SCO2 LMNA CAV1 SDHA LMNA HAMP RYR1 CASR MYH7 TRIM37 KIF1B LMNA PTEN SURF1 ACTN2 MYH7 RET LMNA ATXN7 LMNA SLC19A2 GTF2I RPS19 MYH7 TRNF STAT1 GTPBP3 PPARG TRNV TMEM127 LDB3 MAX TBX20 TRNS1 COX2 MDH2 SCO1 MYLK2 GJA1 HFE NDUFS2 GK TTN ELAC2 HNRNPA2B1 IDS TBX20 TRNE MAX NSMCE2 ACAD9 TRNK CYTB GATA4 ND5 GLA ADCY5 HBA1 HADHB SNAP29 MYH7 NKX2-5 SLC22A5 SDHC HBB CITED2 HLA-DRB1 HNRNPA1 ABCC6 SDHB SLC25A3 ALMS1 CP VCP SCN4A HBB FH FBN1 DTNA FOS PRKAR1A TF SDHB COG7 VHL TLL1 PPARG FLNA ENG PSEN1 CCN2 MYPN GPR35 BAZ1B JUP EPG5 SLC25A11 RET CLIC2 COX3 FBLN5 SLC17A5 CAV3 NKX2-5 CEP19 TMEM43 PEX7 SMAD4 PHYH CYTB SCN1B MYSM1 ADAMTSL2 PRKAR1A TRNL1
HP:0001945: Fever
Genes 374
NLRP3 PSMB4 CHD7 NABP1 PTPN22 TRNK MTHFR ND6 GALC IGH SCYL1 LIFR TREX1 BCAP31 EIF2B5 G6PD NPM1 ZBTB16 ABCC2 EPB41 CTRC DDB2 CD247 ADAMTS13 POU6F2 ND2 IFNG NTRK1 LAMA3 SCNN1A IKZF1 ND1 SLC29A3 TNFRSF1A RAG2 NLRP3 CFTR CRLF1 TP53 MALT1 CD70 ATM CACNA1S TCF4 SLC19A3 PRSS1 IL12B HLA-DPA1 JAK2 XPA CPT2 PRSS2 CFTR IL10 NAB2 ATP13A2 NCF4 REST WIPF1 NLRP3 NCF2 IGH SPTA1 SCNN1B CHEK2 H19 PTPN3 CYBC1 HTR1A BCOR LAMC2 RYR1 RAG2 TMEM165 RNASEH2C RARA DST IL6 PMM2 NCF1 CYP11B2 CD3D COX1 UNC93B1 RB1 TRAF3 MPL PSMB8 EIF2B4 IL36RN MYD88 GCH1 TH TSC1 GAA CYBA HLA-DPB1 RIPK1 NLRP12 STAT4 SPTA1 MLX TRIP13 AVP CFHR1 ELANE MPL AVPR2 P4HTM ND4 IGLL1 MST1 SLC22A4 PTS LPIN1 TRIM28 TCF3 HNRNPK IGHM CD79A PIK3R1 NOD2 MTHFR RANBP2 RYR1 LACC1 AVPR2 STAT5B STXBP2 TRNW CD79B CTLA4 NLRP3 TET2 SPTB EIF2B2 HAVCR2 HLA-DRB1 ERCC3 CYBB CD3E BCL2 DIS3L2 FOXP1 IL23R COX2 SPINK1 STAT3 GLA PRKAR1A KCNJ1 RNF168 COX3 IL7R NLRP3 TRNV FBP1 STAT2 HBB IGH GALC STX11 MEFV SLC12A3 BACH2 LPIN2 STAT3 ATP1A2 CFH CALR SLC35C1 WT1 LIFR PEX6 TRNW PRTN3 EPB42 HMGCL MEFV NOD2 HLA-B TRNS1 DCLRE1C NGLY1 IBA57 TLR4 TRNH JAK2 RAG1 ORAI1 PMP22 CYBC1 MVK AQP2 PRNP ATP1A3 CACNA1A TREX1 MEFV GATA2 ERCC2 BRCA2 OTULIN BCR ND5 IRF2BP2 IFIH1 IFNGR1 WAS RYR1 CASK NLRC4 PSAP ERCC5 ZFHX2 NLRP3 SAMHD1 COL1A1 ND1 SH3KBP1 ASAH1 SLC29A3 LACC1 TCIRG1 ND4 TNFRSF1A MEFV ACAT1 STING1 STAT4 EDA SRP54 ELP1 LAMB3 VANGL2 RMRP IRF8 IRAK1 C4A QDPR TRNQ COL1A1 KLHL7 CCND1 CCR1 UNC13D EIF2B1 UBAC2 BTK BIRC3 HNRNPK MEFV CD27 TP53 ADA RNASEH2B FAS NLRC4 CFHR3 PSMB9 BCL10 TNFAIP3 PRF1 TICAM1 ND3 VANGL2 PSTPIP1 BCL6 SLC4A1 NUMA1 PADI4 CACNA1S JAK2 HMBS TRNT1 CYP21A2 SCNN1G F5 MIF NTRK1 EIF2B3 ALPL ITK CALR ERAP1 RAB27A WDR1 HBB SPP1 MYD88 TRNL1 TLR3 ADA2 LBR IRF8 HLA-DRB1 PTPN22 TET2 STIM1 KIF1B LYST PML TRIM28 TRNF ADAR NLRP3 GYPC FIP1L1 RAG1 STAT6 TBK1 ELANE ND5 HAVCR2 HMGCL TBL1XR1 COG6 KLRC4 PTPN22 AQP2 XIAP ND6 HLA-B RNASEH2A TRNS2 IL2RG SPTB NLRP1 POLR3A HLA-DRB1 LIG4 AK2 IL10 HLA-DRB1 PRKCD MVK NKX2-1 KRT18 LRRC8A SLC12A1 IL12A-AS1 ABL1 KRT8 GPC3 ELANE LPIN2 GPR35 CYP11B2 CIITA RUNX1 BLNK TSC2 WT1 IL2RG IL7R ERCC4 ATP6 ANK1 SH2B3 IL12A CD244 LIPA RAB27A GFI1 NGF SLC11A1 CYTB POMP NFKBIL1 BTNL2 XPC HLA-B TRNL1 PRKAR1A
HP:0002664: Neoplasm
Genes 1522
SF3B1 GFI1B IGF2 FIBP RPS7 WT1 COL7A1 TREX1 HSPG2 CASP8 SLC22A18 MC1R TFE3 KRAS PLAG1 OFD1 BRAF NUMA1 KRT16 PSENEN CTPS1 APC SOX9 FANCM OPCML CDKN2A RPS15A CTNNB1 SDHD EDN3 FCN3 NELFA GJC2 MALT1 HPGD GLI1 CD70 SPINK1 LETM1 PMS1 LRP5 HNF1B EXT1 TCF4 ELMO2 MET ANTXR1 KRT16 KRT10 PAX4 SETBP1 TERT WT1 SMARCB1 GJB6 HRAS STK11 BUB1B GNPTAB MYD88 MCC GJB2 BRCA1 TP63 PDGFRL TARS1 NF1 FGFR3 KARS1 BARD1 BRIP1 GATA2 IL1RN BRAF CD81 TNFRSF13B TYROBP AR LIG4 KLF11 ABL1 MVK BMPR1A PIK3CA B3GALT6 SLC37A4 SOS1 TSC1 FGFR3 ATRX FANCG TET2 KIT SRP72 MPL TP53 SMAD4 EVC2 MAPRE2 DLST BRCA1 DICER1 HRAS AKT1 RNR1 TSC1 TNPO3 XRCC4 DNMT3A NEUROD1 THPO MN1 NOD2 SRSF2 PPM1D FLT4 ATP7A IL7 KRAS GDNF WNT10A EPAS1 COL1A1 IL1B MRAP ADAMTS3 PRKCD SUFU PTCH1 ERCC3 KRT14 CXCR4 HOXD13 IGF2 LIG4 PALB2 BLM NRAS ERCC3 FOXP1 SDHD TP53 PKD2 PDX1 TINF2 ADA2 MYF6 RHBDF2 POU6F2 PHKG2 CDKN2A RUNX1 ERCC2 MAP2K2 WT1 USB1 GATA4 FGFR2 ACD CR2 MUTYH ARL6IP6 FAH MSH2 RASA1 NEK1 SOX6 NR0B1 LIG4 CDKN2B NF1 NF1 POLE RPL35 SRY SDHAF2 FANCL CPLX1 FAS PRKAR1A PHB SDHA CALR PIK3R1 FAN1 TET2 TMEM216 RSPO1 SEMA3D MDM4 SDHD HRAS NUP214 GJA1 PIK3CA CCND1 RNF6 MSH2 C11ORF95 MVK MCM4 FLI1 TINF2 KIAA0753 ECM1 ARSA ERCC2 SOX2 SDHC SLC26A2 MPL VANGL1 PUF60 RAD51D POT1 CR2 ESCO2 FOXE1 PMVK SRY GJB4 TRIM37 KIT EXT2 PDGFB KIF1B FANCF IGF2R MLH1 GDNF PIK3CA ASCC1 ASCL1 TCIRG1 APPL1 RPS19 BCL10 IGF2 NRAS FLT3 STAT1 BCL10 RMRP GNAI3 KRAS GPR101 BAP1 NKX2-1 MAX BMPR1A DDB2 SMARCB1 RAD51 FGFR3 ALX4 BTK MSH6 NOTCH3 DICER1 CXCR4 CCBE1 RET WT1 TP53 PALLD RNASEH2B WT1 ATR CCND1 KCNQ1OT1 SMAD4 AHCY STK11 FANCC TRNK BCL6 SMAD4 SKIV2L HMBS TP53 TERT PHOX2B SNAI2 BRAF TCOF1 FANCI NRAS REST SDHC HBB HFE CREBBP MET SEC23A CEP57 CTLA4 TRIM28 SMAD7 GNAS BRCA2 PALB2 FGF8 SBDS RET ALK GJB2 CPLANE1 GPC3 TCTN3 PTEN RB1 INTU CYP26C1 LEMD3 PRLR CDON NLRP1 GPR101 DHH HNF4A MMEL1 DNASE1L3 RASGRP1 ATRX CHEK2 FANCA SPRED1 DNM2 FLT4 CHEK2 RPS19 KLLN HACE1 HNF1A PTPN11 CDKN1B GAS1 BRCA2 KCNQ1OT1 NPM1 FGFR3 MC1R MINPP1 PTPN11 TSC2 ABCA5 BRCA2 PLCB4 SCN11A HNF1A BRAF RB1 CBL ARHGAP26 SUFU PTPRJ C1S APC IRF5 GNAQ GDNF TERT MYSM1 XPC TMC8 COL4A5 ERBB3 SLC26A4 CD96 NSUN2 PDGFRA FERMT1 TYR DNAJC21 MSH2 SH3GL1 TUBB RET BRAF ESR1 PAX3 RHBDF2 RTL1 WRN DYNC2LI1 ELANE EXOC6B RPS26 EWSR1 VHL PIGA GCGR POU6F2 RNF43 POLE BRAF MNX1 SFTPA2 CDH23 ASCL1 APC ACVR1 PIGL BAX RAG2 RSPO1 MSH3 PGM3 FGF3 FANCE MPL TP53 COL7A1 BUB1 TET2 PALB2 ACTB PNP SDHC EDN3 XPA TMC6 NEK1 GNA11 KAT6B KRT1 RUNX1 PAX7 NOTCH1 ENG CTNNB1 ETV6 MPLKIP PARN CDKN2A PTPN3 STAG3 MDM2 TP53 LAMC2 NBEAL2 VAMP7 GNA14 DCLRE1C CBL GCDH FANCC AXIN2 PYGL SOS1 BLK WRAP53 IDH1 KRAS CCM2 APC ASXL1 ATP7B ERCC3 SF3B1 EP300 BRCA2 MGAT2 NRTN CDKN2A DICER1 PMS1 RPS10 TBC1D24 FAH BRCA2 ASXL1 BCR C2CD3 KRAS IDH1 IGLL1 RASA1 BRCA2 CHEK2 PTCH1 RNF113A BRAF MBTPS2 EDNRB IGHM PDGFRB RAF1 MEN1 FASLG TUBB NDUFAF6 FOXI1 TGFBR1 EPCAM CYLD SDHB APC CYP2D6 TAF1 KRT17 BRCA1 BUB1B BAP1 GDF2 BUB1B ERCC2 TP53 KRT5 GATA2 BRCA1 RAD54B MRE11 STAC3 DNMT3A MLH1 BCHE EDN3 CDKN1B AURKA NRAS FLCN IDH2 EDN1 ESCO2 USF3 IGH POT1 ACVRL1 JAK2 NBN NRAS SQSTM1 TMEM127 ZFPM2 SLC12A3 NTHL1 ADA CHIC2 STAT3 SETBP1 FANCB FIBP STAT3 STK11 MLLT10 SFTPC HDAC4 NUP214 GLI2 SLX4 TSC1 ERCC6 TP53 CLCNKB KLF6 OGG1 JAK2 PAX6 RECQL4 RPL31 MYO1H FH RPGRIP1L SLC45A2 RPL10 RPL10 HMBS GDF5 TNFRSF10B PIK3CA GABRD TP53 BRCA2 SEMA4A BCR PALB2 ASXL1 KRT6B CCDC22 SAMD9 DMPK DCC ERCC5 RPL5 CTNNB1 RPS27 TRNS2 PTCH1 PTEN TFAP2A RPS24 RPL35A RET AXIN1 HNF1B ARMC5 UBE2T SRP54 SSX2 DKC1 ERCC3 JAK2 GNA11 LAMB3 GJB2 NFKB1 KCNQ1 GLI3 PIK3CA KANSL1 CASP8 MYC RECQL4 ACAN CACNA1S BDNF KIF11 MDH2 MSL3 FGFR1 TERF2IP HFE NFKB2 TOP2A GFI1 SRD5A3 PHKA2 MAX POLE MAP2K1 EYA1 RNF43 ALX3 SETD2 ERCC4 CTLA4 SIX3 LEMD3 OCRL CDH23 DZIP1L MSH3 AR CDC73 PDGFRL TWIST1 POU2AF1 DKC1 CALR LIN28B KRT6A GATA1 MC1R DIS3L2 CD28 CDC73 ADA2 UROD CIB1 TSR2 WNT5A TET2 PHOX2B BMPER KIT DLC1 MSTO1 H19-ICR SLC25A13 ADAR TMEM67 BMPR1A MLH3 POLR1C KRT6B FH EFL1 TERC BUB3 FOXC2 NOTCH3 KIT NSD1 FGFR2 SLC6A17 MAP3K1 TRIP13 MEG3 RRAS2 BMPR1A NF1 DPM1 LIG4 PARN RHOH BRCA2 NF1 TAF15 RFWD3 VHL H19 BCR KRAS VANGL2 KRAS SDHD DVL3 BIN1 ABL1 GPC3 HAX1 FANCA GDNF NHP2 IGF2 VHL CCL2 EXTL3 RUNX1 PRKCD BLNK MSH6 SLC22A18 IL2RG PTH1R SDHB AIP WDPCP APC KCNJ10 ASPSCR1 OCA2 TP53 WT1 SPRTN TET2 TAL1 L2HGDH KIT SDHC ERCC4 GPR143 PRKN SMAD4 SEMA3C TRNS1 BRCA1 SHOX PCNA FANCG CREB1 TRNH VHL MYLK BAP1 SUFU ANTXR1 POLD1 NODAL IGH JAK2 MS4A1 MEN1 TSC2 GATA2 DHCR7 TINF2 F13B RB1 COL7A1 SCN4A BMPR1A DDB2 CDKN2A SDHD CYP11B2 IL7 ARID1B KIT FGFR1 RET CDKN2A LAMA3 CHEK2 TBX2 TBX18 HNF4A GPC4 SHH LMNA BMP2 YY1 AKT1 WT1 BAP1 FZD2 SH2B3 BTK GATA1 RAD54L ATM CTBP1 PTEN SRY RYR1 CTHRC1 MFN2 PTEN RAD21 PTEN MYC SLC26A2 TP53 CTNNB1 RAD51C NAB2 NLRP1 SUFU DLL1 PSAP SDHB REST TGFBR2 TRIP13 IGH ABCC8 IL6 CPLANE1 H19 FANCD2 FGFR2 RET PKD1 DNMT3A REST CHEK2 GNAQ MXI1 BRIP1 DYNC2LI1 GNAS TP53 GLI3 DIS3L2 NRAS PICALM WT1 BAP1 MEN1 TXNRD2 MGMT PTEN MYD88 GNAS POT1 AGGF1 BUB1 PTEN PORCN HFE NUTM1 PHOX2B MSX2 PMS2 SLX4 H19 USP9X RPL27 GNAS SEC23B CBL CD28 PKHD1 AXIN2 TRPV3 KLLN SSX1 TSC1 PPOX KRT17 CARD14 HRAS TCF3 RPL11 CC2D2A GREM1 CHEK2 AP2S1 NRAS TRNL1 ALX1 CREBBP TCTN3 TET2 ESCO2 DOCK8 NRAS STK11 GCM2 TTC37 WT1 SMAD4 DAXX MITF BCL2 DIS3L2 POLR1D TDGF1 KRAS TNFRSF13C KIT PHOX2B SF3B1 RPL15 NF1 TERT TNFRSF1B FANCD2 MLH3 IL7R GPC4 H19-ICR SLC17A9 MEN1 MST1R KIT RAD50 TJP2 DNAJC21 PDCD10 MUTYH IL12RB1 SH2D1A FGFR2 NBN KRAS KIT CASR ENPP1 SDHB HRAS IKBKG PNP EXT2 BRD4 SMARCB1 REST COL11A2 TG KIT LIG4 SUFU NBN RSPRY1 CYSLTR2 SDHD AAGAB BLM RAG1 RNF139 RB1CC1 ACD PTPN11 SLC26A2 TREX1 BMPR1B DDR2 ZAP70 MNX1 MAGT1 AIP GATA2 AR STAR IFIH1 IDH2 BRCA1 USP8 RB1 FGFRL1 SMO USP8 RMRP SLC25A11 MLH3 FUZ DOCK8 SUFU NF2 KDR KRAS RPS14 CASP10 SRP54 ZSWIM6 TBXT PTCH2 EWSR1 TNFRSF13C MTAP NQO2 RPL18 DNAJC21 GCK ERCC6 KDM6B EXT1 SBDS CCND1 SDHAF2 KCNH1 CYLD LMOD1 PDGFRA CAT CHRNG TRNQ ADA NRAS TLR2 SHOX FGFR3 BCL10 TYR KRAS COL2A1 PTCH2 SMO GBA MSTO1 TREM2 JAK2 TMEM231 MSH2 ASXL1 RET DHCR7 NBN PIK3CA NSD2 SDHB EIF2AK4 PALB2 KIF7 PTPN11 PIK3CA HLA-DRB1 STIM1 TMC6 KIF1B TNFSF15 RELA AKT1 NPM1 APC SDHA SDHB STAT6 CDKN1C CDC73 PTCH2 KANSL1 ZSWIM6 FLCN HBB LZTS1 FN1 TRAF7 ACP5 CTNNB1 MLH1 EXT2 RNASEL RNASEH2A IL2RG ATP7A CDK4 CYP11B1 MMP1 SDHB ATRX ACTG2 FOXH1 OFD1 NEK9 STS MUC5B PRKCD PTPN11 PTCH2 LRRC8A RPL26 MSH6 NNT LZTR1 CDC73 PTEN AKT1 AKT1 SASH1 HRAS ANAPC1 PTPN12 KCNJ11 TCF4 GATA2 MLH3 ERCC4 GNB1 DISP1 IDH1 BCR GANAB MSH6 NR5A1 TSC2 GFI1 TNFSF12 TRNP MAPK1 IFNG FLT4 MTM1 WWOX HABP2 RPS28 HRAS SLCO2A1 ND5 SDHB CHD7 BRIP1 SLC37A4 MC2R XRCC3 TNFRSF4 NAGS PHF21A ZIC2 PCGF2 SMARCE1 CTNNB1 SRP54 CDH1 CDK4 RPS20 KCNJ10 RAD21 RNF6 COL14A1 SMO CD19 WRN SRGAP1 CDKN2C AXIN2 GPC6 WWOX HSPA9 FOXI1 CPOX RPS17 APC2 MYH8 SERPINA1 ATM LMX1B ENG POLH TGFBR2 DHX37 VEGFC KIF1B KRT17 DDX41 SPIB CBFB HRAS BCL10 PIGL FGFR1 NSD1 F5 KCNN3 BAX PIEZO2 RECQL4 CREBBP KIT PDGFB PDE6D ABCA5 AKT1 KLHDC8B TNFSF12 EPCAM RARA MLH1 GINS1 EVC PIK3CA FANCE WIPF1 NF2 PDGFRA PRKAR1A CDH1 SDHD PRCC TRNF PTCH1 TNFRSF1B WNT10A WWOX MAD1L1 MTOR WDPCP RNASEH2C NSD2 SAMD9L FH LPP NF1 KRIT1 NTHL1 IL12A HNF1A CDH1 SMARCB1 SMARCE1 CD19 FH FDPS TRPS1 ERCC4 SMPD1 SMARCD2 BRCA1 MPL CRKL SEC23A EXT1 PERP ATM FOXE1 CDKN2B CTSC SIX1 FAM149B1 CDH1 RAD51C ALX3 DLST TRIP13 ING1 PDGFRB FLT3 COL18A1 MST1 TGIF1 TMEM107 SRSF2 TRIM28 BAP1 ANTXR2 CD79A PIK3R1 MAP3K1 NOP10 PIK3CA POLD1 KDSR CCND1 TP53 TMC8 ALK MAP2K1 CD79B SDHC ECE1 PALLD CTSA PRDM16 IVNS1ABP CALR FLNA GPR101 BRCA2 ERCC2 DYNC2H1 TFAP2A COL2A1 DVL1 TERT APC TERT TEK EXT2 TERC ALX4 OFD1 LMO1 PDGFRB RPS14 DCC RTEL1 INS TSC2 FAM20C MYH11 GPC3 SCN9A SMAD4 RASGRP1 HBB TGFBR2 RERE NDP PLA2G2A TCF4 MAD2L2 SKI AIP HMMR SDHC SNAI2 PIK3CA LMNA PGM3 ABCB11 TAL2 WT1 VHL PIK3CA TCTN3 SAMD9L ICOS GLI3 RB1 SLC25A13 SDHC DCLRE1C GCM2 VANGL1 SIX6 WT1 PMS2 KCNH1 BARD1 H19-ICR GNAS TERT CIB1 B3GALT6 GJB3 ERBB2 SDHA KRAS CDC73 TNFRSF13B TET2 FGFR3 WAS SEC23B TGFBR2 TP53 NF2 SMARCA4 NF2 SLC26A4 ANTXR2 WRAP53 FAS SAMHD1 TP53 TET2 ATP7A PTEN SH3KBP1 CARMIL2 MVD PDGFB ABCC6 G6PC1 TRNK KRAS GPC3 PTEN NF2 JAK2 DMRT3 GNAQ RAD51 GTF2H5 TMEM127 TERT RUNX1 FAT4 AR HABP2 NR4A3 EP300 MINPP1 OFD1 RASA1 DLEC1 BIRC3 AIP CD27 PHOX2B BMPR1A KCNE3 PLCD1 RAD51 KRT1 MSH3 MITF EPHB2 DHCR24 RABL3 KRT17 XRCC2 NRAS ITK VHL BICC1 RECQL4 SMARCAD1 MYCN RET CTC1 PTCH1 JAK2 SRC SDHB PHOX2B AKT1 KEAP1 JAG1 VHL LETM1 NLRP1 MEN1 BRCA2 FLCN C2CD3 RFWD3 XPA APC APC SDHD FOXO1 MAFA WHCR GPC4 MLH1 ICOS CDKN1B MTMR14 KIT DICER1 EP300 ZFHX3 MMP1 PRKAR1A KRT9 F13A1 CTNNB1 MPL INPP5E NF1 DKC1 TERT DLK1 SCN10A STS RPS29 PTEN FLCN LRBA ELANE GTF2E2 ATM PIK3CA GPR35 CYLD RAD51C CDKN1A WT1 DICER1 PIK3CA TERC PIK3CA SLC25A11 GNAS CEBPA ATP6V1B2 RET XPC EXT1 BRCA2 SH2B3 ERCC3 BRCA2 RTEL1 WASHC5 ERCC2 AKT1 KCNAB2 CYLD STK4 POLH ERCC5 CDH1 CEL XIAP MSR1 TP53 TET2 DHH PRKAR1A