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

NCT ID: NCT01810315

Last Updated: 2015-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2014-10-31

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).

Conditions

HIV Prevention

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Baseline

Premenopausal women will undergo baseline sampling in each the follicular and luteal phase. Postmenopausal women will undergo baseline sampling one time.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

TFV 1% gel

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Estradiol vaginal cream

Intervention Type: DRUG

TFV 1% gel and estradiol 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.

Group Type: EXPERIMENTAL

TFV 1% gel

Intervention Type: DRUG

Estradiol vaginal cream

Intervention Type: DRUG

Interventions

TFV 1% gel

Intervention Type: DRUG

Estradiol vaginal cream

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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

• 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

• 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

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

CONRAD

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Research Center, Eastern Virginia Medical School

Norfolk, Virginia, United States

Countries

United States

Other Identifiers

A12-124

Identifier Type: -

Identifier Source: org_study_id