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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Microbicide Trials Network
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00705679

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 II

MedlinePlus related topics: AIDS

Drug Information available for: Adenine Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Truvada

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study
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

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 ]

Estimated Enrollment:	4200
Study Start Date:	July 2009
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 14 to 35 months	Drug: Emtricitabine/tenofovir disoproxil fumarate placebo placebo tablet Drug: Tenofovir disoproxil fumarate 300 mg tablet
2: Experimental TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 14 to 35 months	Drug: Emtricitabine/tenofovir disoproxil fumarate 200 mg/300 mg tablet Drug: Tenofovir disoproxil fumarate placebo placebo tablet
3: Experimental TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 14 to 35 months	Drug: Emtricitabine/tenofovir disoproxil fumarate placebo placebo tablet Drug: Tenofovir disoproxil fumarate placebo placebo tablet
4: Experimental Application of tenofovir 1% vaginal gel once daily	Drug: Tenofovir 1% vaginal gel 1 gm/100 ml of 1% gel
5: Experimental Application of tenfovir placebo gel once daily	Drug: Tenofovir placebo placebo gel

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 14 months to a maximum of 35 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. Pharmacokinetic studies will occur at some visits. A pap smear will occur at select visits.

Eligibility

Ages Eligible for Study:	18 Years to 40 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 infection 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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Microbicide Trials Network

Investigators

Study Chair:	Zvavahera M. Chirenje, MD, FCROG	UZ-UCSF Collaborative Research Programme
Study Chair:	Jeanne Marrazzo, MD, MPH	University of Washington, Division of Allergy and Infectious Disease

More Information

Additional Information:

Click here for more information about Emtricitabine/tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information on tenofovir This link exits the ClinicalTrials.gov site

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for the Microbicide Trials Network Web site This link exits the ClinicalTrials.gov site

Publications:

Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006 Feb 28;20(4):543-51.

Rosen RK, Morrow KM, Carballo-Diéguez A, Mantell JE, Hoffman S, Gai F, Maslankowski L, El-Sadr WM, Mayer KH. Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial: a mixed-methods study. J Womens Health (Larchmt). 2008 Apr;17(3):383-92.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	MTN-003, 1-U01-AI068633-02
Study First Received:	June 24, 2008
Last Updated:	September 29, 2008
ClinicalTrials.gov Identifier:	NCT00705679 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Microbicide
HIV Seronegativity

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases

Emtricitabine
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Emtricitabine
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

Tenofovir disoproxil
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on May 06, 2009