Rectal Safety and Acceptability Study of Tenofovir 1% Gel

MTN-007 is a Phase 1, randomized, blinded, placebo-controlled safety and acceptability study of vaginally formulated tenofovir 1% gel (a reduced-glycerin formulation), when applied rectally. The primary objective of this study is to assess the safety of vaginally formulated tenofovir 1% gel when applied rectally. This study will also determine whether rectal use of tenofovir 1% gel is associated with rectal mucosal damage using a broad range of immunological safety biomarkers, utilizing N-9 as a positive control, as rectal application of N-9 is known to cause mild but transient mucosal damage. Other secondary objectives include evaluations of the acceptability of rectal administration of tenofovir 1% gel as well as the safety of hydroxyethylcellulose (HEC) placebo gel when applied rectally. Participants will be randomized to receive a single dose of tenofovir 1% gel, 2% N-9 gel or a placebo gel that is applied by a clinician at the study site. The study will also include a no treatment arm. There will be 15 participants in each arm. Participants will return to the clinic, where they will self-administer a single dose of the study gel under observation. Within approximately 30 minutes, lavage, stool, and rectal biopsy specimens will be obtained. After a one-week recovery period, participants will return to the clinic for assessment. If no significant adverse events (AEs) are reported they will begin to self-administer once-daily outpatient doses of the study gel for 7 days. Participants will return to the clinic for evaluation and specimen collection after completion of 7 days of daily dosing. Receptive anal intercourse is common among men who have sex with men and there is increasing evidence that heterosexual women in the developed and developing world also practice anal sex. It can therefore be anticipated that once vaginal microbicides are licensed, they will be used in both the vaginal and rectal compartments. As a consequence, there is a need to evaluate both the rectal and vaginal safety profile of candidate microbicides. The Rectal Microbicide Program clinical protocols have therefore been developed to assess the safety and pharmacology of tenofovir 1% gel when used rectally in men and women as well as address critical questions regarding rectal microbicides through exploratory objectives.