A Comparative Pre-Phase I Study of the Impact of Gel Vehicle Volume on Distal Colon Distribution, User Experience, and Acceptability
For persons at risk of HIV infection who practice receptive anal intercourse (RAI), topical rectal microbicides represent a promising option for coitally-dependent protection. The study compared colorectal distribution and user sensory experiences of two different volumes of rectal gel for suitability as rectal microbicide. Eight HIV negative men with a history of recent RAI were enrolled into a two-period, sequence randomized, dosing study comparing 3.5 mL and 10 mL of radiolabeled (1 mCi 99mTc-DTPA) universal placebo hydroxyethyl cellulose (HEC) gel. Each participant received two doses in the research unit, one of each volume, separated by a washout period of at least 2 weeks. Each research unit dose was followed by a self-administered take-home dose in the context of preparing for RAI. Safety and gastrointestinal distribution were assessed after the research unit doses; safety, perceptibility, and acceptability were assessed after take-home doses. There were no adverse effects of Grade 2 or higher and all resolved spontaneously. Both volumes were well tolerated and received high acceptability scores. Perceptibility scores showed meaningful effect size differences ranging from Cohen’s d=.5 to d=1.2. The 3.5 mL and 10 mL gel volumes distributed similarly (p>0.2) within the rectosigmoid ranging from 0.69 cm to 18.84 cm and 1.21 cm to 19.01 cm from the anorectal junction, respectively. Both volumes covered the typical gastrointestinal distribution of ejaculate following simulated intercourse based on other studies. Either of these gel volumes could reasonably be pursued for the next phase of development of rectal microbicides.