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A Randomized, Open Label, Crossover Phase 1 Safety and Pharmacokinetic Study of Oral Maraviroc and Maraviroc 1% Gel (the CHARM-03 Study).

The CHARM-03 study was a randomized, open label, crossover Phase 1 safety and pharmacokinetic study of oral maraviroc and maraviroc 1% Gel. At a single site, healthy HIV-uninfected men and women were enrolled and randomized to an open label crossover sequence of eight consecutive daily exposures to MVC 300 mg dosed orally, MCV 1% gel dosed rectally, and MVC 1% gel dosed vaginally. Assessments were undertaken at baseline and following each eight-day period and included collection of plasma, rectal/cervical tissue, and rectal/endocervical/vaginal fluids. Eleven men and nine women were enrolled. Two participants withdrew from the study before receiving study product. There were 25 adverse events (AEs), of which 24 were Grade 1 (G1) and one was G2 (unrelated). After eight doses, MVC was quantifiable in all samples following oral, rectal, or vaginal product administration. The highest drug concentrations in plasma, rectal tissue, and cervical tissue were associated with oral, rectal, and vaginal drug delivery respectively. There were significant reductions in tissue drug concentrations when biopsies were incubated in media prior to tissue processing for PK (p<0.0001). Only oral MVC was associated with limited protection in the rectal explant HIV challenge model (p<0.05). There were no immunological changes in rectal tissue, and all products were acceptable to participants. In conclusion, all products were found to be safe and acceptable and did not induce local inflammation. The lack of ex vivo efficacy demonstrated in study samples may be due to rapid disassociation of MVC from the explant tissue.