- Evaluate the safety of reduced glycerin (RG) tenofovir 1% gel when applied rectally
MTN-007 was a Phase 1, randomized, blinded, placebo-controlled safety and acceptability study of RG tenofovir 1% gel when applied rectally. This study also examined whether rectal use of RG tenofovir 1% gel was associated with rectal mucosal damage using a broad range of immunological safety biomarkers. Nonoxynol-9 (N-9) 2% gel was used as a positive control for mucosal damage as rectal application of 2% N-9 was previously shown to cause mild but transient mucosal damage. Other secondary objectives included evaluations of the acceptability of rectal administration of tenofovir RG 1% gel as well as the safety of HEC placebo gel when applied rectally. Sixty evaluable participants were enrolled and randomized to receive a single dose of RG tenofovir 1% gel, 2% N-9 gel, HEC placebo gel, or no treatment, to be self-administered under observation. Within approximately 30 minutes, lavage, stool, and rectal biopsy specimens were collected. After a one-week recovery period, participants returned to the clinic for assessment. If no significant adverse events (AEs) were reported, participants began to self-administer once-daily doses of study gel for seven days on an outpatient basis. Participants returned to the clinic for evaluation and specimen collection after completion of seven days of daily dosing.
MTN-007 completed follow-up on July 20, 2011. Results were presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) held on March 5-8, 2012, in Seattle, WA. The primary manuscript was published in PLoS One on April 3, 2013. A total of three papers have been published from this study.
Reduced Glycerin tenofovir 1% gel was found to be safe and well-tolerated. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms.
US National Institute of Mental Health
US National Institutes of Health
Phase 1 randomized, double-blinded, multi-site, placebo-controlled trial