Adherence and Acceptability to and Blood Levels of Tenofovir Gel and Tablets in HIV Uninfected Women

HIV Infections Clinical Trial

Official title:

Phase 2 Adherence and Pharmacokinetics Study of Oral and Vaginal Preparations of Tenofovir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00592124
• Other study ID #: MTN-001
• Secondary ID: 106171U01AI06863
• Status: Completed
• Phase: Phase 2
• Start date: June 2008
• Est. completion date: July 2010

Study information

• Verified date: January 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Tenofovir disoproxil fumarate
300 mg tablet daily
• Tenofovir gel
1 gm/100 ml of 1% gel vaginally daily

Locations

Country	Name	City	State
South Africa	Botha's Hill CRS	Durban	KwaZulu-Natal
South Africa	Umkomaas CRS	Durban	KwaZulu-Natal
Uganda	Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS	Kampala
United States	Alabama Microbicide CRS	Birmingham	Alabama
United States	Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)	Bronx	New York
United States	Case CRS	Cleveland	Ohio
United States	Pitt CRS	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Microbicide Trials Network

Countries where clinical trial is conducted

United States,  South Africa,  Uganda, 

References & Publications (3)

Bateman C. Tenofovir gel--the new HIV prevention 'banker'? S Afr Med J. 2007 Jul;97(7):496, 498. Review. — View 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 — View Citation

Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Mâsse 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Self-reported Adherence to Each Regimen	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.	Measured through Week 21
Primary	Proportion of Participants Who Indicate They Would be "Unlikely" Use Study Product in the Future		Measured through Week 21
Primary	Systemic and Local PK Among Three Regimens of Tenofovir (Oral, Vaignal, and Dual Use)	PK measures, including maximum concentrations (Cmax) in serum, tissue, and cervicovaginal lavage.	Measured through Week 21
Secondary	Frequency of Product Use	This number represents how often participant used study product during the preceding 3 weeks and is measured twice during each 6 week product period.	Measured through Week 21
Secondary	Number of Days Product Missed	This represents the longest number of days in a row during the past 3 weeks that a participant missed using the study product.	Measured through Week 21
Secondary	Proportion of Women Who Report Taking at Least 90% of Expected Daily Doses		Measured through Week 21
Secondary	Frequency of Sexual Activity	This represents the rate during the past 3 weeks at which participants engaged in vaginal sex.	Measured through Week 21
Secondary	Frequency of Male Condom Use		Measured through Week 21
Secondary	Tablet Usage Before Sex	These summaries represent counts and percentages of participants using tablet before last instance of vaginal sex.	Measured through Week 21
Secondary	Length of Time Vaginal Sexual Intercourse Took Place After Using Tablet.	Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given tablet was used before the encounter).	Measured through Week 21
Secondary	Tablet Usage After Sex	These summaries represent counts and percentages of participants using tablet after last instance of vaginal sex.	Measured through Week 21
Secondary	Length of Time Vaginal Sexual Intercourse Took Place Before Using Tablet.	Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given tablet was used after the encounter).	Measured through Week 21
Secondary	Gel Usage Before Sex	These summaries represent counts and percentages of participants using gel before last instance of vaginal sex.	Measured through Week 21
Secondary	Length of Time Vaginal Sexual Intercourse Took Place After Using Gel.	Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given gel was used before the encounter).	Measured through Week 21
Secondary	Gel Usage After Sex	These summaries represent counts and percentages of participants using gel after last instance of vaginal sex.	Measured through Week 21
Secondary	Length of Time Vaginal Sexual Intercourse Took Place Before Using Gel.	Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given gel was used after the encounter).	Measured through Week 21
Secondary	Reported Sharing of Product	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.	Measured through Week 21
Secondary	Grade 3 or Higher Toxicity for Systemic and Local Effects as Defined by the Protocol		Measured through Week 21

External Links

•   Click here for the Microbicide Trials Network Web site