A Phase 1 Randomized, Blinded Comparison of the Pharmacokinetics and Colonic Distribution of Three Candidate Rectal Microbicide Formulations of Tenofovir 1% Gel with Simulated Unprotected Sex (CHARM-02)

摘要: Abstract CHARM-02 is a crossover, double-blind, randomized trial to compare the safety and pharmacokinetics of three rectally applied tenofovir 1% gel candidate rectal microbicides varying osmolalities: vaginal formulation (VF) (3111 mOsmol/kg), reduced glycerin (RGVF) (836 mOsmol/kg), an isoosmolal rectal-specific (RF) (479 mOsmol/kg). Participants (n = 9) received single, 4 ml, radiolabeled dose each twice, once with without simulated unprotected receptive anal intercourse (RAI). The safety, plasma pharmacokinetics, colonic small molecule permeability, SPECT/CT imaging lower gastrointestinal distribution drug virus surrogate were assessed. There no Grade 3 or 4 adverse events reported for any products. Overall, there more 2 in VF group compared RF (p = 0.006) RGVF (p = 0.048). In absence RAI, had up 3.8-fold greater systemic ex...