This is a phase 1, 2-part, global, multicenter, open-label, PK, safety and tolerability study of oral tazemetostat in subjects with either advanced solid tumors, or hematological malignancies and normal hepatic function or moderate, or severe hepatic impairment.
Name: Tazemetostat
Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration Time: 0 to 72 hours post dose on Day 1 and Day 15Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-∞: area under the plasma concentration-time curve from time 0 extrapolated to infinity Time: 0 to 72 hours post dose on Day 1 and Day 15Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-72: area under the plasma concentration-time curve from time 0 to 72 hours post dose Time: 0 to 72 hours post dose on Day 1 and Day 15Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, Cmax: observed maximum plasma concentration Time: 0 to 72 hours post dose on Day 1 and Day 15Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, Tmax: observed time at Cmax Time: 0 to 72 hours post dose on Day 1 and Day 15Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, λz: terminal phase elimination rate constant Time: 0 to 72 hours post dose on Day 1 and Day 15Description: When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Measure: To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, t1/2: terminal elimination half-life Time: 0 to 72 hours post dose on Day 1 and Day 15Description: Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of tazemetostat will be evaluated by the Investigator based on the CTCAE, version 5.0
Measure: To evaluate the number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 Time: Through study completion, an average of 1 yearDescription: Investigators will note any new clinically significant findings (e.g., not noted at screening) or changes in intensity of conditions that occurred after the initial tazemetostat administration
Measure: To evaluate the number of abnormalities or changes in intensity of conditions noted during the physical exam Time: Through study completion, an average of 1 yearDescription: Investigators will note any clinically significant changes from baseline in systolic and diastolic blood pressure measured in units of millimeters of mercury (mmHg)
Measure: To evaluate change in blood pressure Time: Through study completion, an average of 1 yearDescription: Investigators will note any clinically significant changes from baseline in heart rate measured in units of beats per minute (BPM)
Measure: To evaluate change in heart rate Time: Through study completion, an average of 1 yearDescription: Investigators will note any clinically significant changes from baseline in body temperature measured in degrees Fahrenheit or Celsius
Measure: To evaluate change in body temperature Time: Through study completion, an average of 1 yearDescription: Investigators will note any changes in concomitant medications from baseline in all subjects with at least 1 dose or partial dose of tazemetostat
Measure: To evaluate changes in concomitant medications Time: Through study completion, an average of 1 yearDescription: Investigators will report any clinically significant changes from baseline in the RR interval (sec) as noted by a 12 lead electrocardiogram (ECG)
Measure: To evaluate change in electrical activity of the heartbeat, RR interval Time: Through study completion, an average of 1 yearDescription: Investigators will report any clinically significant changes from baseline in the PR interval (sec) as noted by a 12 lead electrocardiogram (ECG)
Measure: To evaluate change in electrical activity of the heartbeat, PR interval Time: Through study completion, an average of 1 yearDescription: Investigators will report any clinically significant changes from baseline in the QRS complex (sec) as noted by a 12 lead electrocardiogram (ECG)
Measure: To evaluate change in electrical activity of the heartbeat, QRS complex Time: Through study completion, an average of 1 yearDescription: Investigators will report any clinically significant changes from baseline in the QT interval (sec) as noted by a 12 lead electrocardiogram (ECG)
Measure: To evaluate change in electrical activity of the heartbeat, QT interval Time: Through study completion, an average of 1 yearDescription: Investigators will note any clinically significant changes in hematological clinical laboratory values from baseline in all subjects with at least 1 dose or partial dose of tazemetostat using laboratory reference ranges
Measure: To evaluate changes in clinical laboratory values, hematology Time: Through study completion, an average of 1 yearDescription: Investigators will note any clinically significant changes in serum chemistry clinical laboratory values from baseline in all subjects with at least 1 dose or partial dose of tazemetostat using laboratory reference ranges
Measure: To evaluate changes in clinical laboratory values, serum chemistry Time: Through study completion, an average of 1 yearDescription: Investigators will note any clinically significant changes in urinalysis clinical laboratory values from baseline in all subjects with at least 1 dose or partial dose of tazemetostat using laboratory reference ranges
Measure: To evaluate changes in clinical laboratory values, urinalysis Time: Through study completion, an average of 1 yearAllocation: N/A
Single Group Assignment
There is one SNP
JAK2 V617F) observed in cytogenetic testing and DNA sequencing 12. --- V617F ---