HIV Prevention
Conditions
Keywords
Microbicides, Tenofovir, Reduced-glycerin, Vaginal use, Rectal use, Pharmacokinetics
Brief summary
To compare local and systemic pharmacokinetics of tenofovir reduced-glycerin (TFV RG) 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use
Interventions
DRUGOnce Daily Application of TFV RG 1% Gel - Vaginal
Vaginal application
DRUGOnce Daily Application of TFV RG 1% gel - Rectal
Rectal application
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
CONRAD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 21 through 45 years (inclusive) at Screening 2. Able and willing to provide written informed consent 3. Able and willing to comply with all study procedure requirements, including, clinical and laboratory assessments, vaginal and rectal examinations, urine and blood testing, as well as attendance at all scheduled study visits 4. In general good health at Screening and Enrollment as determined by the Investigator of Record (IoR)/ or designee 5. Negative pregnancy test at Screening and Enrollment 6. HIV-negative at Screening and Enrollment 7. Able and willing to provide adequate locator information 8. Willingness to use study-provided male condoms for the duration of study participation for penetrative intercourse 9. Per participant report at Screening, regular menstrual cycles with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera, progesterone-containing IUDs or extended use of oral contraceptives) 10. Per participant report at Enrollment, using an effective method of contraception and intending to use an effective method for the duration of study participation; effective methods include: * Hormonal methods, excluding vaginal rings * Intrauterine device (IUD) inserted at least 42 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions) * Sterilization of participant or partner at least 42 days prior to Enrollment * Self-identifies as a woman who has sex with women exclusively * Sexually abstinent for the at least 90 days prior to enrollment and the intention to remain sexually abstinent for the duration of study participation 11. Per participant report at Screening, states a willingness to refrain from inserting any non-study vaginal or rectal products or objects into the vagina or rectum, including but not limited to, spermicides, female condoms, diaphragms, contraceptive vaginal rings, vaginal medications, menstrual cups, cervical caps (or any other vaginal barrier method), vaginal/rectal douches, enemas, non-study approved lubricants, sex toys (vibrators, dildos, etc.), and tampons for the duration of the study product use periods and for 24 hours prior to each scheduled study clinic visit. 12. Pap result consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) or satisfactory evaluation of non-Grade 0 Pap result with no treatment required per clinical judgment of IoR or designee in the 12 calendar months prior to the Enrollment Visit 13. At Screening, participant agrees not to take part in other research studies involving drugs, medical devices, or vaginal/rectal products for the duration of study participation (including the time between the Screening and Enrollment visits) Participants in the biopsy subset must also meet the following criteria at Screening to be eligible for inclusion: 14. Willing to abstain from inserting anything into the vagina or rectum for 72 hours prior to and following the collection of these samples, including vaginal and rectal intercourse 15. Willing to restrict the use of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and/or other drugs that are associated with the increased likelihood of bleeding following mucosal biopsy collection for 72 hours prior to and following the collection biopsies
Exclusion criteria
1. Participant report of any of the following: 1. Known adverse reaction to the study product (ever) 2. Known adverse reaction to latex (ever) 3. Current male sex partner with known history of adverse reaction to latex (ever) 4. History of serum HBsAg positivity (ever) 5. Non-therapeutic injection drug use in the 12 calendar months prior to Enrollment 6. Sexually transmitted infections (STI) or reproductive tract infection (RTI) requiring treatment in the 6 calendar months prior to Enrollment 7. Post-exposure prophylaxis (PEP) for possible HIV-1 infection within the 6 calendar months prior to Enrollment 8. Last pregnancy outcome within 90 days or less prior to Enrollment 9. Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage) within the 42 days prior to Enrollment Note: This does not include biopsy for the evaluation of an abnormal pap result or endometrial biopsy that occurred more than 7 days prior to Enrollment, provided that all other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug concentrations | 10 weeks | To compare local and systemic pharmacokinetics of tenofovir reduced-glycerin 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events Grade 2 or higher | 10 weeks | To assess the safety of tenofovir reduced-glycerin 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use |
Other
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of HIV by study drug in rectal and genital fluids | 10 weeks | Correlate drug levels in rectal and genital fluids with drug potency |
| Microflora biomarkers and gene expression from the vaginal and rectal environments | 10 weeks | Determine changes in microflora biomarkers and gene expression from the vaginal and rectal environments after 2 weeks of daily rectal versus 2 weeks of daily vaginal use of tenofovir reduced-glycerin 1% gel at sites with capacity |
Countries
United States
Outcome results
None listed