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 7, 2012
Last verified: September 2012
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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:
Genetics Home Reference related topics:
complement factor I deficiency
MedlinePlus related topics:
HIV/AIDS
Drug Information available for:
Formic acid
Emtricitabine
Tenofovir
Tenofovir Disoproxil Fumarate
Truvada
U.S. FDA Resources
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:
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:
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:
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:
|
|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00705679
Locations
| South Africa | |
| Wits Reproductive Health and HIV Institute (WRHI) CRS | |
| Johannesburg, Gauteng, South Africa, 2038 | |
| Soweto MTN CRS | |
| Johannesburg, Gauteng, South Africa | |
| Botha's Hill CRS | |
| Durban, KwaZulu-Natal, South Africa, 3660 | |
| Umkomaas CRS | |
| Durban, KwaZulu-Natal, South Africa, 4170 | |
| Isipingo CRS | |
| Durban, KwaZulu-Natal, South Africa, 4110 | |
| Verulam CRS | |
| Durban, KwaZulu-Natal, South Africa, 4340 | |
| Overport CRS | |
| Durban, KwaZulu-Natal, South Africa, 4091 | |
| CAPRISA eThekwini CRS | |
| Durban, KwaZulu-Natal, South Africa, 4011 | |
| Chatsworth CRS | |
| Durban, KwaZulu-Natal, South Africa, 4030 | |
| Tongaat CRS | |
| Tongaat, KwaZulu-Natal, South Africa, 4400 | |
| CAPRISA Aurum CRS | |
| Klerksdorp, South Africa, 2571 | |
| Uganda | |
| Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS | |
| Kampala, 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: | September 7, 2012 |
| 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 March 14, 2013
