A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study).

摘要: Objectives The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (TFV) gels for rectal application. The vaginal formulation (VF) gel was previously used in CAPRISA 004 VOICE microbicide Phase 2B trials RMP-02/MTN-006 1 safety study. reduced glycerin VF (RGVF) MTN-007 trial is currently being evaluated MTN-017 2 trial. A third specific (RF) also study. Methods Participants received 4 mL TFV a blinded, crossover design: seven daily doses RGVF, RF, six placebo followed by one dose VF, randomized sequence. Safety, compartmental PK, explant PD were monitored throughout trial. Results All found to be safe acceptable. RF RGVF PK not significantly different. Median mucosal mononuclear cell (MMC) TFV-DP trended toward higher values compared (1136 320 fmol/106 cells respectively). Use each vivo associated with significant inhibition ex colorectal tissue HIV infection. There negative correlation between levels TFV, TFV-DP, MMC fluid HIV-1 infection. Conclusions formulations However, profile only based on exposure whereas participants gels. trend towards use gel. all infection. Trial Registration ClinicalTrials.gov NCT01575405