HPTN 066

Dose-Proportionality and Intra-Individual Variability of Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate in Healthy Volunteers

What is HPTN 066?

Protocol Status: Re-Opened

Study Summary

Study Purpose: Describe the dose-proportionality and intra-individual variability of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) at steady-state in healthy human participants taking Truvada® (FTC 200mg/TDF 300 mg) under direct observation.

Study Design: Phase 1, multi-site, open label, randomized, 4-arm, dose-ranging, pharmacokinetic (PK) study.

Study Population: HIV-uninfected, healthy, sexually-active volunteers, including both men and women recruited from two sites in the United States (U.S.).

Study Size: 32 participants distributed into four 8-person cohorts with 4 men and 4 women per cohort. 16 of the original 32 participants (2 men, 2 women per dosing cohort), will undergo intensive tissue sampling.

Study Duration: Approximately 12 months total. Accrual will require approximately 6 months. Each participant will be followed for approximately 2 months (screening, treatment, and follow-up).

Treatment Regimen: Research participants will receive doses under the direct observation of study personnel for 5 weeks. Research participants will be enrolled randomly into one of four study arms: (1) FTC 200 mg/TDF 300 mg, one tablet orally once weekly for 5 weeks; (2) FTC 200 mg/TDF 300 mg, one tablet orally twice weekly for 5 weeks; (3) FTC 200 mg/TDF 300 mg, two tablets orally twice weekly for 5 weeks; (4) FTC 200 mg/TDF 300 mg, one tablet once daily for 5 weeks.

Primary Objectives: (1) Assess dose-proportionality of intracellular TFV-DP and FTC-TP from weekly to daily dosing; (2) Describe intra-individual variability in intracellular TFV-DP and FTC-TP concentrations at steady-state (comparison of Day 28 and Day 35).

Secondary Objectives: (1) Describe the relationship between pre-dose (C_tau) and decaying concentrations of TFV, FTC, and their phosphorylated derivatives (TFV-DP and FTC-TP) in blood serum, peripheral blood mononuclear cells (PBMCs), CD4+ blood cells, total tissue cells, CD4+ tissue cells, tissue homogenate, semen, and luminal fluid at steady-state (Day 35 [pre-dose] and Day 49 [decaying, greater than one half-life for TFV-DP]; (2) Describe differences in intracellular TFV-DP and FTC-TP steady-state C_tau between men and women; (3) Characterize the safety profiles of four different TDF/FTC regimens for pre-exposure chemoprophylaxis (PrEP).

SDMC Project Manager: Laura McKinstry get info

Protocol Team Member: Angela Kashuba get info

Protocol Team Member: Cheryl Cokley get info

Protocol Team Member: James Rooney get info

Protocol Team Member: Paul Richardson get info

Protocol Team Member: Rebecca Guzman get info

Protocol Team Member: Susan Eshleman get info

Protocol Team Member: Ying Q. Chen get info

Protocol Statistician: Lei Wang get info

Protocol Co-Chair: Kenneth H. Mayer get info

Protocol Co-Chair: Kristine Patterson get info

Protocol Chair: Craig Hendrix get info

DAIDS Pharmacist: Katie Shin get info

DAIDS Medical Officer: Vanessa Elharrar get info

CORE Protocol Specialist: Ayana Moore get info

CORE Protocol Specialist: Kevin Bokoch get info