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

HIV Prevention Clinical Trial

Official title:

Influence of Female Reproductive Cycle and Menopause on Cervicovaginal Tissue Susceptibility to HIV-1 Infections and Tenofovir 1% Gel Activity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01810315
• Other study ID #: A12-124
• Status: Completed
• Phase: Phase 1
• First received: March 11, 2013
• Last updated: April 9, 2015
• Start date: September 2013
• Est. completion date: October 2014

Study information

• Verified date: April 2015
• Source: CONRAD
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years to 89 Years

Eligibility

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

Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV Prevention

Intervention

Drug:
• TFV 1% gel

• Estradiol vaginal cream

Locations

Country	Name	City	State
United States	Clinical Research Center, Eastern Virginia Medical School	Norfolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
CONRAD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentrations of tenofovir in plasma, vaginal aspirate, and genital tissue		3 hours after dosing	No
Primary	Concentrations of TFV-DP in genital tissue		3 hours after dosing	No