Safety and Effectiveness of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate, and Emtricitabine/Tenofovir Disoproxil Fumarate Tablets in Preventing HIV in Women

This study has been completed.
Sponsor:
Collaborator:
Microbicide Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00705679
First received: June 24, 2008
Last updated: September 30, 2014
Last verified: September 2014

June 24, 2008
September 30, 2014
August 2009
August 2012   (final data collection date for primary outcome measure)
  • Effectiveness of daily tenofovir 1% gel versus vaginal placebo gel measured by HIV seroconversion [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Effectiveness of oral TDF and oral FTC/TDF versus oral placebo measured by HIV seroconversion [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Extended safety of daily tenofovir 1% gel, oral TDF, and oral FTC/TDF in women at risk for sexually transmitted HIV infection based on occurrence of Grade 2, 3, and 4 adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00705679 on ClinicalTrials.gov Archive Site
  • Adherence to daily regimens of vaginal gel versus oral tablets [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Change in sexual activity, condom use, and intravaginal practices over time [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Frequency of HIV-1 drug resistance in women who acquire HIV-1 infection while using study product [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Reported HIV seroconversion, toxicity, viral resistance, cervicovaginal inflammation, or adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Incidence of HIV seroconversion in each study product group [ Time Frame: During the 8 weeks of follow-up off study product ] [ Designated as safety issue: No ]
  • Relationship between plasma drug concentrations and study outcomes using PK-PD models [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Safety and Effectiveness of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate, and Emtricitabine/Tenofovir Disoproxil Fumarate Tablets in Preventing HIV in Women
Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.

It is necessary to monitor both the adherence and blood levels of microbicides in order to gauge its efficacy in a study population. Utilizing an experimental microbicide (tenofovir gel) and anti-HIV drugs (TDF, FTC/TDF), this study will measure the effectiveness and safety to and blood levels of the three interventions in three regimens given to HIV uninfected women.

The expected duration of participation for each participant ranges from a minimum of 12 months to a maximum of 38 months. Study participants will be randomly assigned into one of five study groups, each with a different regimen. Group 1 participants will take one TDF tablet daily and one FTC/TDF placebo tablet daily. Group 2 participants will take one TDF placebo tablet daily and one FTC/TDF tablet daily. Group 3 participants will take one TDF placebo tablet daily and one FTC/TDF placebo tablet daily. Group 4 participants will apply tenofovir 1% gel vaginally once daily. Group 5 participants will apply tenofovir 1% placebo gel vaginally once daily.

Study visits will occur every 28 days after enrollment. Medical history, a physical exam, behavioral and adherence assessment, urine and blood collection, and counseling will occur at all visits. Blood will also be collected and archived for future research at select visits. Pharmacokinetic studies will occur at some visits. A pap smear will occur at select visits. Some participants may have hair samples collected on an optional basis at study visits every 2 months.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
HIV Infections
  • Drug: Emtricitabine/tenofovir disoproxil fumarate
    200 mg/300 mg tablet
    Other Names:
    • FTC/TDF
    • Truvada
  • Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
    placebo tablet
    Other Names:
    • FTC/TDF placebo
    • Truvada placebo
  • Drug: Tenofovir disoproxil fumarate
    300 mg tablet
    Other Name: TDF
  • Drug: Tenofovir disoproxil fumarate placebo
    placebo tablet
    Other Name: TDF placebo
  • Drug: Tenofovir 1% vaginal gel
    1 gm/100 ml of 1% gel
    Other Names:
    • TFV
    • 9-[2-(Phosphonomethoxy)propyl]adenine
  • Drug: Tenofovir placebo
    placebo gel
    Other Name: TFV placebo
  • Experimental: 1
    TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months
    Interventions:
    • Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
    • Drug: Tenofovir disoproxil fumarate
  • Experimental: 2
    TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months
    Interventions:
    • Drug: Emtricitabine/tenofovir disoproxil fumarate
    • Drug: Tenofovir disoproxil fumarate placebo
  • Experimental: 3
    TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months
    Interventions:
    • Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
    • Drug: Tenofovir disoproxil fumarate placebo
  • Experimental: 4
    Application of tenofovir 1% vaginal gel once daily
    Intervention: Drug: Tenofovir 1% vaginal gel
  • Experimental: 5
    Application of tenofovir placebo gel once daily
    Intervention: Drug: Tenofovir placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5029
August 2012
August 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Willing to provide adequate locator information
  • Sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
  • Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for duration of study.
  • Agree to use effective method of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • HIV infected
  • Known adverse reaction to any of the study products
  • Known adverse reaction to latex
  • Pathologic bone fracture not related to trauma
  • Non-therapeutic injection drug use in the 12 months prior to screening
  • Post-exposure prophylaxis for HIV exposure within 6 months prior to enrollment
  • Last pregnancy outcome 42 days or less prior to enrollment
  • Gynecologic or genital procedure 42 days or less prior to enrollment
  • Participation in any other research study involving drugs, medical devices, or vaginal products 30 days or less prior to enrollment
  • Currently using spermicide, interferon or interleukin therapy, or certain medications. More information on this criterion can be found in the protocol.
  • Any significant uncontrolled active or chronic disease. More information on this criterion can be found in the protocol.
  • Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
  • Intends to become pregnant in the 24 months after enrollment
  • Plans to relocate or travel away from the study site for more than 8 consecutive weeks in the 24 months after enrollment
  • Urinary tract infection
  • Pelvic inflammatory disease, an STI, or reproductive tract infection requiring treatment
  • Grade 2 or higher pelvic exam finding
  • Any condition that, in the opinion of the investigator, would interfere with the study
  • Pregnant or breastfeeding
Female
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
South Africa,   Uganda,   Zimbabwe
 
NCT00705679
MTN-003 (VOICE), 10622, MTN-003, 1-U01-AI068633-02, VOICE
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Microbicide Trials Network
Study Chair: Zvavahera M. Chirenje, MD, FRCOG UZ-UCSF Collaborative Research Programme
Study Chair: Jeanne Marrazzo, MD, MPH University of Washington, Division of Allergy and Infectious Disease
National Institute of Allergy and Infectious Diseases (NIAID)
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP