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Report for Clinical Trial NCT00432016

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerance, Pharmacokinetics and Antiviral Activity of Amdoxovir and Zidovudine in Untreated HIV-1 Infected Subjects Currently Untreated

The purpose of this study is to determine the short term safety, tolerance, and antiviral effect of zidovudine (AZT) and amdoxovir (AMDX, DAPD) in combination, and whether the dosage for AZT can be reduced, potentially decreasing side effects, while maintaining antiviral effects. Study hypothesis: DADP in combination with AZT is safe and effective, and AZT dosing may be reduced, resulting in lower levels of AZT-monophosphate associated with toxicity and maintaining levels of AZT-triphosphate associated with efficacy.

NCT00432016 HIV Infections
MeSH: HIV Infections

3 Interventions

Name: zidovudine

Type: Drug

Name: amdoxovir

Type: Drug

Name: pharmacokinetic sampling

Type: Procedure


Primary Outcomes

Measure: Proportion of subjects in each arm with Grade 3 or greater treatment emergent adverse events (AE)

Measure: Plasma Cmax, Cmin, tmax, AUC0→τ, AUC0→∞, t1/2, CL/F of DAPD and AZT in each group at Days 1 and 10

Measure: Intracellular Cmax, Cmin, tmax, AUC0→τ, AUC0→∞, and t1/2 of DXG-TP, -MP and -DP and AZT-TP, -MP, and -DP at Days 1 and 10

Secondary Outcomes

Measure: Change in viral load (plasma HIV-1 RNA) from Baseline through Day 10

Measure: Correlate intracellular DXG-TP and AZT-TP with viral response, as measured by plasma HIV-1 RNA

Measure: Quantitate DXG, AZT, and GAZT in urine with and without DAPD

Measure: Characterize viral rebound (plasma HIV-1 RNA) following drug discontinuation for 48 hr

Measure: Measure CD4+ count changes from Baseline to Day 10

Purpose: Treatment

Allocation: Randomized

Single Group Assignment


There are 2 SNPs

SNPs


1 K65R

Therefore, second line treatments that are currently in development should provide activity against resultant mutations, primarily M184V/I (17%) and much less commonly K65R (0 to 5%), and ideally prevent or be effective against mutations that may occur during second line therapy. --- M184V --- --- K65R ---

AZT offers anti-K65R activity which is believed to be conferred by the 3'-azido moiety containing pseudo-sugar structure and base components of AZT. --- K65R ---

Hence, AZT could potentially be incorporated to prevent the emergence of the K65R mutation that could limit the long-term benefit of DAPD. --- K65R ---

This 10 day, proof of principle, pharmacokinetic study will provide important information about reduced AZT dosing to support the development of an AZT/DAPD co-formulation which may prevent the emergence of K65R mutations. --- K65R ---


2 M184V

Therefore, second line treatments that are currently in development should provide activity against resultant mutations, primarily M184V/I (17%) and much less commonly K65R (0 to 5%), and ideally prevent or be effective against mutations that may occur during second line therapy. --- M184V ---

DAPD has increased sensitivity to M184V/I strains and is active against thymidine analog mutations (TAMs) that may have occurred during previous antiretroviral regimens. --- M184V ---



HPO Nodes