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Adherence and Acceptability to and Blood Levels of Tenofovir Gel and Tablets in HIV Uninfected 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:
NCT00592124
First received: December 31, 2007
Last updated: January 4, 2017
Last verified: January 2017
  Purpose
A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) is an oral, FDA-approved, anti-HIV drug, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the adherence and acceptability to and blood levels of three daily regimens of tenofovir in both oral and gel form.

Condition Intervention Phase
HIV Infections
Drug: Tenofovir disoproxil fumarate
Drug: Tenofovir gel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase 2 Adherence and Pharmacokinetics Study of Oral and Vaginal Preparations of Tenofovir

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Self-reported Adherence to Each Regimen [ Time Frame: Measured through Week 21 ]
    Participant self-reported product use. For each woman, adherence to each regimen was computed by dividing the number of daily doses she reported having taken by the number of doses expect if she were fully adherent.

  • Proportion of Participants Who Indicate They Would be "Unlikely" Use Study Product in the Future [ Time Frame: Measured through Week 21 ]
  • Systemic and Local PK Among Three Regimens of Tenofovir (Oral, Vaignal, and Dual Use) [ Time Frame: Measured through Week 21 ]
    PK measures, including maximum concentrations (Cmax) in serum, tissue, and cervicovaginal lavage.


Secondary Outcome Measures:
  • Frequency of Product Use [ Time Frame: Measured through Week 21 ]
    This number represents how often participant used study product during the preceding 3 weeks and is measured twice during each 6 week product period.

  • Number of Days Product Missed [ Time Frame: Measured through Week 21 ]
    This represents the longest number of days in a row during the past 3 weeks that a participant missed using the study product.

  • Proportion of Women Who Report Taking at Least 90% of Expected Daily Doses [ Time Frame: Measured through Week 21 ]
  • Frequency of Sexual Activity [ Time Frame: Measured through Week 21 ]
    This represents the rate during the past 3 weeks at which participants engaged in vaginal sex.

  • Frequency of Male Condom Use [ Time Frame: Measured through Week 21 ]
  • Tablet Usage Before Sex [ Time Frame: Measured through Week 21 ]
    These summaries represent counts and percentages of participants using tablet before last instance of vaginal sex.

  • Length of Time Vaginal Sexual Intercourse Took Place After Using Tablet. [ Time Frame: Measured through Week 21 ]
    Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given tablet was used before the encounter).

  • Tablet Usage After Sex [ Time Frame: Measured through Week 21 ]
    These summaries represent counts and percentages of participants using tablet after last instance of vaginal sex.

  • Length of Time Vaginal Sexual Intercourse Took Place Before Using Tablet. [ Time Frame: Measured through Week 21 ]
    Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given tablet was used after the encounter).

  • Gel Usage Before Sex [ Time Frame: Measured through Week 21 ]
    These summaries represent counts and percentages of participants using gel before last instance of vaginal sex.

  • Length of Time Vaginal Sexual Intercourse Took Place After Using Gel. [ Time Frame: Measured through Week 21 ]
    Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given gel was used before the encounter).

  • Gel Usage After Sex [ Time Frame: Measured through Week 21 ]
    These summaries represent counts and percentages of participants using gel after last instance of vaginal sex.

  • Length of Time Vaginal Sexual Intercourse Took Place Before Using Gel. [ Time Frame: Measured through Week 21 ]
    Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given gel was used after the encounter).

  • Reported Sharing of Product [ Time Frame: Measured through Week 21 ]
    Number and percentage of participants who had a product sharing event during the 6-week product use period, where a sharing event includes 1) being asked for the study product, or 2) selling, trading, or giving away study product, or 3) having someone take the study product from the participant.

  • Grade 3 or Higher Toxicity for Systemic and Local Effects as Defined by the Protocol [ Time Frame: Measured through Week 21 ]

Enrollment: 168
Study Start Date: June 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Oral tenofovir disoproxil fumarate (TDF) for Weeks 1 through 6, vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF and vaginal tenofovir gel application for Weeks 15 through 20
Drug: Tenofovir disoproxil fumarate
300 mg tablet daily
Other Name: TDF
Drug: Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine
Experimental: 2
Vaginal tenofovir gel application for Weeks 1 through 6, oral TDF for Weeks 8 through 13, and oral TDF and vaginal tenofovir gel application for Weeks 15 through 20
Drug: Tenofovir disoproxil fumarate
300 mg tablet daily
Other Name: TDF
Drug: Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine
Experimental: 3
Oral TDF and vaginal tenofovir gel application for Weeks 1 through 6, oral TDF for Weeks 8 through 13, and vaginal tenofovir gel application for Weeks 15 through 20
Drug: Tenofovir disoproxil fumarate
300 mg tablet daily
Other Name: TDF
Drug: Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine
Experimental: 4
Oral TDF and vaginal tenofovir gel application for Weeks 1 through 6, vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF for Weeks 15 through 20
Drug: Tenofovir disoproxil fumarate
300 mg tablet daily
Other Name: TDF
Drug: Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine
Experimental: 5
Oral TDF for Weeks 1 through 6, oral TDF and vaginal tenofovir gel application for Weeks 8 through 13, and vaginal tenofovir gel application for Weeks 15 through 20
Drug: Tenofovir disoproxil fumarate
300 mg tablet daily
Other Name: TDF
Drug: Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine
Experimental: 6
Vaginal tenofovir gel application for Weeks 1 through 6, oral TDF and vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF for Weeks 15 through 20
Drug: Tenofovir disoproxil fumarate
300 mg tablet daily
Other Name: TDF
Drug: Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily
Other Names:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine

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 an anti-HIV drug (TDF), this study will measure the adherence and acceptability to and blood levels of the two interventions in three separate regimens given to HIV-uninfected women.

The expected duration of participation for each participant is 21 weeks. Study participants will be randomly assigned into one of six study groups, each with a different regimen sequence. Each sequence will consist of three study periods and three wash-out periods. Each study period lasts 6 weeks, followed by a 1 week wash-out period. The regimen assigned for a given study period will include either oral TDF, tenofovir vaginal gel, or both. All participants will be prescribed all three regimens in the order designated by their randomized assignment.

Study visits will occur at Weeks 1, 3, 6, 7, 10, 13, 14, 17, 20, and 21. Medical history, a physical exam, behavioral assessment, and urine, blood, pelvic sample collection, and counseling will occur at all visits. At some study sites rectal swabs may be performed. Counseling will include information regarding contraception, protocol adherence, HIV, HIV/Sexually Transmitted Infection risk reduction, and male condom use. Pharmacokinetic (PK) studies, to be determined by the study site, will occur during all three study periods. These studies may involve additional procedures.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • General good health
  • HIV-uninfected
  • Normal menstrual cycle. More information can be found in the protocol.
  • Creatinine clearance greater than 70 ml/min
  • Sexually active. More information can be found in the protocol.
  • Normal Pap smear result within 12 months prior to study entry
  • Agrees to not participate in other investigational studies
  • Willing to use effective forms of contraception. More information can be found in the protocol.

Exclusion Criteria:

  • Adverse reaction to either of the study products
  • Adverse reaction to latex
  • Currently sexually active with a partner with history of adverse reaction to latex
  • More than three sexual partners in the month prior to screening
  • Pathologic bone fracture not related to trauma
  • Last pregnancy outcome within 90 days or less prior to enrollment
  • Gynecologic or genital procedure within 90 days of study entry
  • Enrollment in other investigational study within 30 days of study entry
  • Nontherapeutic injection drug use within 12 months of screening
  • Any social or medical condition that, in the opinion of the investigator, would interfere with the study
  • Abnormal laboratory values
  • Grade 2 or higher genital lesions, erythema, and/or edema or has any other abnormal physical or pelvic exam finding that, in the opinion of the investigator, would interfere with the study
  • Kidney, reproductive, or urinary tract infection requiring treatment. More information on this criterion can be found in the protocol.
  • Pregnant, breastfeeding, or intend to become pregnant
  • Unwilling to comply with study participation requirements, including attendance at all scheduled study visits
  • Per participant report, use of the following at enrollment, and/or anticipated use during the period of study participation - use of a diaphragm, vaginal ring, and/or spermicide for contraception, acyclovir or valacyclovir, post-exposure prophylaxis for HIV exposure, TDF/emtricitabine, non-study vaginal products
  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: NCT00592124

Locations
United States, Alabama
Alabama Microbicide CRS
Birmingham, Alabama, United States, 35294
United States, New York
Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)
Bronx, New York, United States
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213-2582
South Africa
Botha's Hill CRS
Durban, KwaZulu-Natal, South Africa
Umkomaas CRS
Durban, KwaZulu-Natal, South Africa
Uganda
Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS
Kampala, Uganda
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Microbicide Trials Network
Investigators
Study Chair: Craig W. Hendrix, MD Johns Hopkins University
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00592124     History of Changes
Other Study ID Numbers: MTN-001
10617 ( Registry Identifier: DAIDS ES )
1U01AI068633-01 ( US NIH Grant/Contract Award Number )
Study First Received: December 31, 2007
Results First Received: January 4, 2017
Last Updated: January 4, 2017

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

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

ClinicalTrials.gov processed this record on March 27, 2017