Rectal Microbicide Safety and Acceptability Trial of Topically Applied Tenofovir Compared With Oral Tablet
Status:
Completed
Trial end date:
2010-07-01
Target enrollment:
Participant gender:
Summary
To date, the majority of microbicide research has focused on the assessment of the safety and
effectiveness of vaginal microbicides used for the prevention of HIV transmission via the
vaginal compartment. Receptive anal intercourse (RAI) is common among men who have sex with
men (MSM), 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. Therefore, the primary objective of this study is to evaluate the
systemic safety of 1% vaginally formulated tenofovir gel applied rectally. In addition, this
study will evaluate the immunotoxicity of the gel and evaluate its acceptability; it will
also use the oral tenofovir disoproxil fumarate tablets (TDF), rectally-applied tenofovir
gel,and a placebo gel to compare their systemic and compartmental pharmacokinetic (pK)
profiles.
This study was designed to address the following hypotheses:
- Vaginally-formulated tenofovir 1% topical gel when applied rectally will be safe using a
combination of clinical and laboratory markers including assays specifically designed to
measure mucosal toxicity
- Tenofovir will be detectable at different concentrations in the various anatomic
compartments sampled for pharmacokinetics following single and 7-day topical exposures
- Exposure to tenofovir 1% gel will demonstrate prevention of ex vivo HIV-1 challenge
using in vivo drug-exposed tissue as compared to baseline tissue samples
- Orally delivered, single dose, 300 mg tenofovir disoproxil fumarate tablets will have
similar safety profiles using routine blood safety indices as have been established in
other trials and will show no mucosal safety concerns
- The oral dose will have different multi-compartment concentration kinetics than the
topical tenofovir and will also demonstrate preliminary (ex vivo) prevention using the
explant infectivity assay
- Vaginally formulated tenofovir 1% topical gel applied rectally will be acceptable to
participants, as indicated by a score in the upper one third of the 10-point Likert
scale on intentionality to use in the product in the future
Phase:
Phase 1
Details
Lead Sponsor:
CONRAD
Collaborators:
Microbicide Trials Network National Institute of Allergy and Infectious Diseases (NIAID)