Influence of Reproductive Cycle and Menopause on HIV-1 Infection and TFV Gel Activity

Phase 1

Completed

• Conditions: HIV Prevention
• Interventions: Drug: TFV 1% gel; Drug: Estradiol vaginal cream

• Registration Number: NCT01810315
• Lead Sponsor: CONRAD

Brief Summary

Purpose of the study is to assess tenofovir (TFV) PK and PD endpoints, cervicovaginal safety parameters, susceptibility to HIV-1 infection, and objective measures of vaginal applicator use in premenopausal and postmenopausal women.

Detailed Description

Premenopausal women: Baseline blood and genital samples will be taken in the follicular and luteal phase (visits 2 and 3). The participant will be given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visits 4/4a and 5/5a).

Postmenopausal women: Premenopausal women: Baseline blood and genital samples will be taken (visit 2). The participant will be given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visit 3/3a). Estradiol cream will be distributed at visit 4. Post estradiol blood and genital samples will be taken at Visit 5. The participant will given TFV gel and instructed to insert 2 doses as before, while continuing to use the estradiol cream. Post TFV gel and estradiol cream blood and genital samples will be taken (visit 6/6a).

Study Timeline

• Study First Submitted: 2013-03-11
• Study First Submitted QC: 2013-03-11
• Study First Posted: 2013-03-13
• Study Start: 2013-09
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-09
• Last Update Posted: 2015-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

All volunteers

• In good healthsignificant systemic disease
• Not at risk of an STI, meaning: In a monogamous heterosexual or same sex relationship for at least the last four months with a partner who is not known to be HIV positive and has no known risks for STIs OR sexually abstinent
• Willing and able to comply with study procedures
• Normal Pap smear (by written report) in the past year.

Inclusion Criteria: Premenopausal volunteers

• 21-to-45 years of age
• Not at risk for pregnancy, meaning:
• Regular menstrual cycles (every 24 - 35 days)
• Luteal phase P level of greater than or equal to 3 ng/ml

Inclusion Criteria: Postmenopausal volunteers

• 46-89 years of age OR both ovaries removed at least 30 days prior to Visit 1
• No menstrual periods/vaginal bleeding in the past 12 months OR both ovaries removed at least 30 days prior to Visit 1
• FSH level of greater than or equal to 20 MIU/ml

Exclusion Criteria

All volunteers

• Clinically significant history of an abnormal Pap smear in the past year
• Surgery or biopsy of the vagina or cervix within 30 days
• Current STI or lower genital tract infection
• Current use of chronic immunosuppressants
• Current presence of vulvar, anal and/or vaginal genital warts
• Current tobacco use of any amount
• History of sensitivity/allergy to any component of the study product, topical anesthetic, or allergy to silver nitrate and/or Monsel's solution
• Known bleeding disorder that could lead to prolonged or continuous bleeding
• Grade 1 or higher laboratory abnormality, per the August 2009 update of the DAIDS Table for Grading the Severity of Adverse Events
• Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, antivirals or antiretrovirals.
• Investigator discretion
• Current participation in any other drug or device study

Exclusion Criteria: Premenopausal women

• Use of DMPA in last six months
• Use of any other hormonal contraceptive method without 2 subsequent, normal menses since stopping hormonal contraceptives
• Current use of copper IUD
• Currently pregnant or pregnancy within the past 3 months
• Currently breastfeeding/having breastfed an infant in the last 2 months

Exclusion Criteria: Postmenopausal women

• Use of any hormonal medications in the past 30 days
• Contraindications to vaginal estrogen cream

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
TFV 1% gel and estradiol cream	Estradiol vaginal cream	Postmenopausal women only: Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel. In addition, participants will one gram of estradiol cream into the vagina every other night.
TFV 1% Gel	TFV 1% gel	Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel. Premenopausal women will undergo sampling after TFV gel use in each the follicular and luteal phase. Postmenopausal women will undergo sampling after TFV gel use one time.
Estradiol Vaginal Cream	Estradiol vaginal cream	Post menopausal women only: Participants will insert 2 grams of estradiol cream into the vagina every night for 14 days and then one gram of estradiol cream into the vagina every other night
TFV 1% gel and estradiol cream	TFV 1% gel	Postmenopausal women only: Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel. In addition, participants will one gram of estradiol cream into the vagina every other night.

Primary Outcome Measures

Name	Time	Method
Concentrations of tenofovir in plasma, vaginal aspirate, and genital tissue	3 hours after dosing
Concentrations of TFV-DP in genital tissue	3 hours after dosing

Trial Locations

Locations (1)

Clinical Research Center, Eastern Virginia Medical School; 🇺🇸 Norfolk, Virginia, United States