Adherence and Acceptability to and Blood Levels of Tenofovir Gel and Tablets in HIV Uninfected Women - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Microbicide Trials Network
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00592124

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 II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Crossover Assignment, Pharmacokinetics Study
Official Title:	Phase 2 Adherence and Pharmacokinetics Study of Oral and Vaginal Preparations of Tenofovir

Resource links provided by NLM:

MedlinePlus related topics: AIDS

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

U.S. FDA Resources

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: Throughout study ] [ Designated as safety issue: No ]
Proportion of participants who indicate they would be "unlikely" use study product in the future [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Area under the concentration-time curve (AUC), maximum serum concentrations (Cmax), and minimum serum concentrations (Cmin) during PK studies [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of women who report taking at least 90% of expected daily doses, frequency of use, and number of days product missed [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Frequency of sexual activity and male condom use [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time interval between product usage and sexual intercourse and sequence of product use and sexual intercourse [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Reported sharing and quantity of study product [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Grade 3 or higher toxicity for systemic and local effects as defined by the protocol [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	144
Study Start Date:	June 2008
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Oral tenofovir disproxil 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 Drug: Tenofovir gel 1 gm/100 ml of 1% gel vaginally daily
2: Experimental 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 Drug: Tenofovir gel 1 gm/100 ml of 1% gel vaginally daily
3: Experimental 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 Drug: Tenofovir gel 1 gm/100 ml of 1% gel vaginally daily
4: Experimental 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 Drug: Tenofovir gel 1 gm/100 ml of 1% gel vaginally daily
5: Experimental 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 Drug: Tenofovir gel 1 gm/100 ml of 1% gel vaginally daily
6: Experimental 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 Drug: Tenofovir gel 1 gm/100 ml of 1% gel vaginally daily

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
Genders 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00592124

Locations

United States, Alabama
Alabama Microbicide CRS	Recruiting
Birmingham, Alabama, United States, 35294
Contact: Hala Fawal, MBA, MPH 205-975-8699 hfawal@uab.edu
Principal Investigator: Craig Hoesley, MD
United States, Ohio
Case CRS	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, RN 216-844-8786 MXL6@case.edu
Principal Investigator: Michael M. Lederman, MD
United States, Pennsylvania
Pitt CRS	Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213-2582
Contact: Christine A. Tripoli, BSN, RN 412-647-0771 tripolica@upmc.edu
Principal Investigator: Sharon A. Riddler, MD
Uganda
Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS	Not yet recruiting
Kampala, Uganda
Contact: Mahnaz Motevalli-Oliner
Principal Investigator: Philippa Musoke, MD

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:

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:

Bateman C. Tenofovir gel--the new HIV prevention 'banker'? S Afr Med J. 2007 Jul;97(7):496, 498. Review. No abstract available.

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.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	MTN-001, 1-U01-AI068633-01
Study First Received:	December 31, 2007
Last Updated:	August 14, 2009
ClinicalTrials.gov Identifier:	NCT00592124 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

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions

Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil

ClinicalTrials.gov processed this record on February 04, 2010