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

This study is currently recruiting participants.
Verified December 2013 by CONRAD
Sponsor:
Information provided by (Responsible Party):
CONRAD
ClinicalTrials.gov Identifier:
NCT01813162
First received: March 11, 2013
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
HIV Prevention
Drug: Tenofovir 1% gel
Drug: Vaginal product
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: In Vivo Drug Interaction Pharmacokinetic Study of Tenofovir 1% Gel and Three Commonly Used Vaginal Products

Resource links provided by NLM:


Further study details as provided by CONRAD:

Primary Outcome Measures:
  • TFV concentrations in plasma and genital tissue and TFV-DP concentrations in genital tissue [ Time Frame: Assessments will be after product use (see description) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Vaginal product concentration in plasma [ Time Frame: Assessments will be after product use (see description) ] [ Designated as safety issue: No ]

    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 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.


  • Genitourinary adverse events (AEs) [ Time Frame: Assessments will be after product use (see description) ] [ Designated as safety issue: Yes ]

    Vaginal product alone: Participant will use assigned product per dosing instructions (antifungal cream: 7 days; antimicrobial gel: 5 days; IVR: 21 days). Genitourinary AEs will be assessed by participant report and exam after completion of dosing.

    TFV gel alone: Participant will use TFV gel for 7 days, inserted 2X a day. Genitourinary AEs will be assessed by participant report and exam after completion of dosing.

    Vaginal product & TFV gel: Participant will use assigned product per dosing instructions. TFV gel will be used for 7 days, 2X a day. Genitourinary AEs will be assessed by participant report and exam after completion of dosing.



Estimated Enrollment: 54
Study Start Date: December 2013
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tenofovir 1% 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.
Drug: Tenofovir 1% gel
Active Comparator: Vaginal product alone

Participants will use their assigned vaginal product for 5 to 7 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 7 days; return to clinic for removal on day 7. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen).
Drug: Vaginal product
Other Names:
  • Terconazole 0.4%
  • Metronidazole gel
  • Contraceptive IVR
Experimental: Vaginal product and Tenofovir 1% gel

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 7 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 7 days; return to clinic for removal on day 7. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen).
Drug: Tenofovir 1% gel Drug: Vaginal product
Other Names:
  • Terconazole 0.4%
  • Metronidazole gel
  • Contraceptive IVR

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Nugent score greater than or equal to 7 or 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
  • Chronic or acute vulvar or vaginal symptoms
  • Known current drug or alcohol abuse which could impact study compliance
  • Grade 2 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 2 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 (e.g., acyclovir or valacyclovir) or antiretrovirals (e.g., Viread®).
  • Participation in any other drug or device interventional investigational trial (device, drug, or vaginal trial) within 30 days of this study or planned participation in any other investigational trial during the study
  • History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix within the last 14 days
  • Abnormal finding on laboratory or physical examination or a social or medical condition which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01813162

Locations
United States, California
Dept of OBGYN and Reproductive Sciences, UCSF Recruiting
San Francisco, California, United States
Contact: Nicole Ureda    415-848-1316      
Principal Investigator: Ariane van der Starten, PhD, MPH         
Principal Investigator: Karen Smith-McCune, MD. PhD         
United States, New York
Bronx-Lebanon Hospital Center Not yet recruiting
Bronx, New York, United States
Principal Investigator: Jessica Justman, MD         
Sponsors and Collaborators
CONRAD
Investigators
Study Chair: Jill Schwartz, M.D. CONRAD
  More Information

No publications provided

Responsible Party: CONRAD
ClinicalTrials.gov Identifier: NCT01813162     History of Changes
Other Study ID Numbers: A11-118
Study First Received: March 11, 2013
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Contraceptive Agents
Metronidazole
Terconazole
Tenofovir
Tenofovir disoproxil
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Radiation-Sensitizing Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Antifungal Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 17, 2014