In Vivo Drug Interaction Pharmacokinetic Study of Tenofovir 1% Gel and Three Commonly Used Vaginal Products

NCT01813162 | Completed Phase 1

• 1 other identifier: A11-118
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the study is determine if the local release characteristics and systemic exposure to tenofovir (TFV) 1% gel and a given commonly used vaginal product are impacted by concomitant use

Conditions

HIV Prevention

Outcome Measures

Primary Outcomes (1)

• TFV concentrations in plasma and genital tissue and TFV-DP concentrations in genital tissue

  Vaginal product alone: Participant will use assigned product per dosing instructions (antifungal cream: 7 days; antimicrobial gel: 5 days; IVR: 21 days). In cream or gel cohorts, blood will be drawn 6 hrs after last use. In contraceptive ring cohort, blood will be drawn after 21 days of use at 0/4,6,10\&24 hrs. TFV gel alone: Participant will use TFV gel for 7 days, inserted 2X a day. In cream/gel cohorts blood will be drawn 4 hrs after last TFV gel use. In contraceptive ring cohort blood will be drawn 4,6,10\&24 hrs after last TFV gel use. Vaginal biopsy will occur 6 hrs after last TFV gel use for all. Vaginal product \& TFV gel: Participant will use assigned product per dosing instructions. TFV gel will be used for 7 days, 2X a day. In gel/cream cohorts blood will be drawn 4 hrs after last TFV gel use. In contraceptive ring cohort blood will be drawn 4,6,10\&24 hrs after last dose of TFV gel. Vaginal biopsy will occur 6 hrs after the last dose of TFV gel for all.

  Assessments will be after product use (see description)

Secondary Outcomes (2)

• Vaginal product concentration in plasma

  Assessments will be after product use (see description)

• Genitourinary adverse events (AEs)

  Assessments will be after product use (see description)

Study Arms (3)

Tenofovir 1% gel

ACTIVE COMPARATOR

Participants will vaginally insert 1 applicator of TFV gel twice a day for 7 days, with each dose inserted approximately 12 hours after the previous dose (for a total of 13 doses). Each applicator contains 4.4 gm of TFV 1% gel.

Drug: Tenofovir 1% gel

Vaginal product alone

ACTIVE COMPARATOR

Participants will use their assigned vaginal product for 5 to 21 days depending on the dosing instructions for the particular product: 1. Terconazole 0.4% vaginal cream: once a day for seven days. 1 applicator (5 gm) of terconazole cream contains 20 mg terconazole. 2. Metronidazole gel: once a day for 5 days. 1 applicator (5 gm)of metronidazole gel contains 37.5 mg metronidazole. 3. Contraceptive IVR: insert ring and leave in place for 21 days; return to clinic for removal on day 21. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen).

Drug: Vaginal product

Vaginal product and Tenofovir 1% gel

EXPERIMENTAL

Tenofovir gel: Participants will vaginally insert 1 applicator of TFV gel twice a day for 7 days, with each dose inserted approximately 12 hours after the previous dose (for a total of 13 doses). Each applicator contains 4.4 gm of TFV 1% gel. In addition, Participants will use their assigned vaginal product for 5 to 21 days depending on the dosing instructions for the particular product: 1. Terconazole 0.4% vaginal cream: once a day for seven days. 1 applicator (5 gm) of terconazole cream contains 20 mg terconazole. 2. Metronidazole gel: once a day for 5 days. 1 applicator (5 gm)of metronidazole gel contains 37.5 mg metronidazole. 3. Contraceptive IVR: insert ring and leave in place for 21 days; return to clinic for removal on day 21. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen). Use of TFV gel will begin on day 15 of IVR use.

Drug: Tenofovir 1% gel; Drug: Vaginal product

Interventions

Tenofovir 1% gel DRUG

Tenofovir 1% gel; Vaginal product and Tenofovir 1% gel

Vaginal product DRUG

Also known as: Terconazole 0.4%, Metronidazole gel, Contraceptive IVR

Vaginal product alone; Vaginal product and Tenofovir 1% gel

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50 years, inclusive
• General good health (by volunteer history and per investigator discretion)
• History of and currently regular menstrual cycles
• Willing to abstain from the use of vaginal products, other than the TFV gel and her assigned study vaginal product for the duration of the study.
• Willing to abstain from sex and other vaginal activity during each crossover period starting 72 hours prior to initiating product use, for the duration of use, and until the sixth day following sample collection
• At low risk for pregnancy due to surgical sterilization of participant and/or her sexual partner, use of copper IUD or male condom, abstinence, or same sex relationship
• Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection
• History of Pap smears and follow-up consistent with ACOG practice guidelines
• Negative urine pregnancy test
• Willing to give voluntary consent, sign an informed consent form and comply with study procedures as required by the protocol

You may not qualify if:

• History of hysterectomy
• Currently pregnant/within 2 calendar months from the last pregnancy outcome.
• Use of Depo-Provera in the last 120 days or any hormonal contraceptives in the last month
• Currently breastfeeding or having breastfed an infant in the last 2 months, or planning to breastfeed during the course of the study
• History of sensitivity/allergy to any component of:
• TFV 1% gel; or
• topical anesthetic, or allergy to both silver nitrate and Monsel's solution.
• Contraindication to any of 3 vaginal products (antifungal cream, antimicrobial gel, or the combination contraceptive vaginal ring) to which participants may be randomized
• In the last 6 months, diagnosed with or treated for any STI or pelvic inflammatory disease, by self report.
• Symptomatic BV
• Positive test for Trichomonas vaginalis at Visit 1
• Positive test for Neisseria gonorrhea or Chlamydia trachomatis
• Positive test for HIV
• Positive test for Hepatitis B surface antigen (HBsAg)
• Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy

Sponsors & Collaborators

• CONRAD: lead

Study Sites (2)

Dept of OBGYN and Reproductive Sciences, UCSF

San Francisco, California, United States

Location

Bronx-Lebanon Hospital Center

The Bronx, New York, United States

Location

MeSH Terms

Interventions

Tenofovir; Gels; Menstrual Hygiene Products

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Feminine Hygiene Products; Equipment and Supplies

Study Officials

• Jill Schwartz, M.D.

  CONRAD

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 18, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 22, 2015

Record last verified: 2015-05

Locations

US (2)