Clinical trial NCT00592124: Adherence and Acceptability to and Blood Levels of Tenofovir Gel and Tablets in HIV Uninfected Women
Official title: Phase 2 Adherence and Pharmacokinetics Study of Oral and Vaginal Preparations of Tenofovir
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Microbicide
HIV Seronegativity
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Microbicide Trials Network
First posted: 2008-01-11
Enrollment: 168
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Self-reported Adherence to Each Regimen
timeFrame: Measured through Week 21
measure: Proportion of Participants Who Indicate They Would be "Unlikely" Use Study Product in the Future
timeFrame: Measured through Week 21
measure: Systemic and Local PK Among Three Regimens of Tenofovir (Oral, Vaignal, and Dual Use)
timeFrame: Measured through Week 21
Secondary outcomes:
measure: Frequency of Product Use
timeFrame: Measured through Week 21
measure: Number of Days Product Missed
timeFrame: Measured through Week 21
measure: Proportion of Women Who Report Taking at Least 90% of Expected Daily Doses
timeFrame: Measured through Week 21
measure: Frequency of Sexual Activity
timeFrame: Measured through Week 21
measure: Frequency of Male Condom Use
timeFrame: Measured through Week 21
measure: Tablet Usage Before Sex
timeFrame: Measured through Week 21
measure: Length of Time Vaginal Sexual Intercourse Took Place After Using Tablet.
timeFrame: Measured through Week 21
measure: Tablet Usage After Sex
timeFrame: Measured through Week 21
measure: Length of Time Vaginal Sexual Intercourse Took Place Before Using Tablet.
timeFrame: Measured through Week 21
measure: Gel Usage Before Sex
timeFrame: Measured through Week 21
measure: Length of Time Vaginal Sexual Intercourse Took Place After Using Gel.
timeFrame: Measured through Week 21
measure: Gel Usage After Sex
timeFrame: Measured through Week 21
measure: Length of Time Vaginal Sexual Intercourse Took Place Before Using Gel.
timeFrame: Measured through Week 21
measure: Reported Sharing of Product
timeFrame: Measured through Week 21
measure: Grade 3 or Higher Toxicity for Systemic and Local Effects as Defined by the Protocol
timeFrame: Measured through Week 21
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Microbicide CRS
state: Alabama
city: Bronx
country: United States
facility: Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)
state: New York
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
city: Durban
country: South Africa
facility: Botha's Hill CRS
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Umkomaas CRS
state: KwaZulu-Natal
city: Kampala
country: Uganda
facility: Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS
Study officials:
affiliation: Johns Hopkins University
name: Craig W. Hendrix, MD
role: STUDY_CHAIR
References:
citation: Bateman C. Tenofovir gel--the new HIV prevention 'banker'? S Afr Med J. 2007 Jul;97(7):496, 498. No abstract available.
citation: 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. doi: 10.1097/01.aids.0000210608.70762.c3.
citation: Hendrix CW, Chen BA, Guddera V, Hoesley C, Justman J, Nakabiito C, Salata R, Soto-Torres L, Patterson K, Minnis AM, Gandham S, Gomez K, Richardson BA, Bumpus NN. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLoS One. 2013;8(1):e55013. doi: 10.1371/journal.pone.0055013. Epub 2013 Jan 30.
citation: Minnis AM, van der Straten A, Salee P, Hendrix CW. Pre-exposure Prophylaxis Adherence Measured by Plasma Drug Level in MTN-001: Comparison Between Vaginal Gel and Oral Tablets in Two Geographic Regions. AIDS Behav. 2016 Jul;20(7):1541-8. doi: 10.1007/s10461-015-1081-3.
citation: Minnis AM, Gandham S, Richardson BA, Guddera V, Chen BA, Salata R, Nakabiito C, Hoesley C, Justman J, Soto-Torres L, Patterson K, Gomez K, Hendrix CW. Adherence and acceptability in MTN 001: a randomized cross-over trial of daily oral and topical tenofovir for HIV prevention in women. AIDS Behav. 2013 Feb;17(2):737-47. doi: 10.1007/s10461-012-0333-8.