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: March 12, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
Drug: Tenofovir disoproxil fumarate
Drug: Tenofovir disoproxil fumarate placebo
Drug: Tenofovir 1% vaginal gel
Drug: Tenofovir placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 5029
Study Start Date: August 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
Drug: Emtricitabine/tenofovir disoproxil fumarate
200 mg/300 mg tablet
Other Names:
  • FTC/TDF
  • Truvada
Drug: Tenofovir disoproxil fumarate placebo
placebo tablet
Other Name: TDF 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
Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
placebo tablet
Other Names:
  • FTC/TDF placebo
  • Truvada placebo
Drug: Tenofovir disoproxil fumarate placebo
placebo tablet
Other Name: TDF placebo
Experimental: 4
Application of tenofovir 1% vaginal gel once daily
Drug: Tenofovir 1% vaginal gel
1 gm/100 ml of 1% gel
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine
Experimental: 5
Application of tenofovir placebo gel once daily
Drug: Tenofovir placebo
placebo gel
Other Name: TFV placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705679

Locations
South Africa
Soweto MTN CRS
Johannesburg, Gauteng, South Africa
Wits Reproductive Health and HIV Institute (WRHI CRS)
Johannesburg, Gauteng, South Africa, 2001
Overport CRS
Asherville, KwaZulu-Natal, South Africa, 4091
Chatsworth CRS
Chatsworth, KwaZulu-Natal, South Africa, 4030
eThekwini CRS
Durban, KwaZulu-Natal, South Africa, 4001
Tongaat CRS
Tongaat, KwaZulu-Natal, South Africa, 4400
Umkomaas CRS
Umkomaas, KwaZulu-Natal, South Africa, 4170
Verulam CRS
Verulam, KwaZulu-Natal, South Africa, 4340
Isipingo CRS
Westville, KwaZulu-Natal, South Africa, 3630
Botha's Hill CRS
Westville, KwaZulu-Natal, South Africa, 3630
CAPRISA Aurum CRS
Klerksdorp, South Africa, 2571
Uganda
MU-JHU Research Collaboration CRS
Kampala, Mpigi, Uganda
Zimbabwe
Seke South CRS
Chitungwiza, Zimbabwe
Zengeza CRS
Chitungwiza, Zimbabwe
Spilhaus CRS
Harare, Zimbabwe
Sponsors and Collaborators
Microbicide Trials Network
Investigators
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
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00705679     History of Changes
Other Study ID Numbers: MTN-003 (VOICE), 10622, MTN-003, 1-U01-AI068633-02, VOICE
Study First Received: June 24, 2008
Last Updated: March 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Microbicide
HIV Seronegativity

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 23, 2014