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

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Tenofovir disoproxil fumarate

Tenofovir gel

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring Microbicide, HIV Seronegativity

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

Alabama Microbicide CRS
Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)
Case CRS
Pitt CRS
Botha's Hill CRS
Umkomaas CRS
Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Proportion of Participants Who Indicate They Would be "Unlikely" Use Study Product in the Future

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.

Secondary Outcome Measures

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.

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.

Proportion of Women Who Report Taking at Least 90% of Expected Daily Doses

Frequency of Sexual Activity

This represents the rate during the past 3 weeks at which participants engaged in vaginal sex.

Frequency of Male Condom Use

Tablet Usage Before Sex

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.

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

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.

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

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.

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

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.

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

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

Full Information

NCT ID

NCT00592124

First Posted

December 31, 2007

Last Updated

October 15, 2021

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Microbicide Trials Network

1. Study Identification

Unique Protocol Identification Number

NCT00592124

Brief Title

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

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

July 2010 (Actual)

Study Completion Date

July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Microbicide Trials Network

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

Microbicide, HIV Seronegativity

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

168 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Tenofovir disoproxil fumarate

Other Intervention Name(s)

TDF

Intervention Description

300 mg tablet daily

Intervention Type

Drug

Intervention Name(s)

Tenofovir gel

Other Intervention Name(s)

TFV, 9-[2-(Phosphonomethoxy)propyl]adenine

Intervention Description

1 gm/100 ml of 1% gel vaginally daily

Primary Outcome Measure Information:

Title

Self-reported Adherence to Each Regimen

Description

Time Frame

Measured through Week 21

Title

Proportion of Participants Who Indicate They Would be "Unlikely" Use Study Product in the Future

Time Frame

Measured through Week 21

Title

Systemic and Local PK Among Three Regimens of Tenofovir (Oral, Vaignal, and Dual Use)

Description

PK measures, including maximum concentrations (Cmax) in serum, tissue, and cervicovaginal lavage.

Time Frame

Measured through Week 21

Secondary Outcome Measure Information:

Title

Frequency of Product Use

Description

This number represents how often participant used study product during the preceding 3 weeks and is measured twice during each 6 week product period.

Time Frame

Measured through Week 21

Title

Number of Days Product Missed

Description

This represents the longest number of days in a row during the past 3 weeks that a participant missed using the study product.

Time Frame

Measured through Week 21

Title

Proportion of Women Who Report Taking at Least 90% of Expected Daily Doses

Time Frame

Measured through Week 21

Title

Frequency of Sexual Activity

Description

This represents the rate during the past 3 weeks at which participants engaged in vaginal sex.

Time Frame

Measured through Week 21

Title

Frequency of Male Condom Use

Time Frame

Measured through Week 21

Title

Tablet Usage Before Sex

Description

These summaries represent counts and percentages of participants using tablet before last instance of vaginal sex.

Time Frame

Measured through Week 21

Title

Length of Time Vaginal Sexual Intercourse Took Place After Using Tablet.

Description

Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given tablet was used before the encounter).

Time Frame

Measured through Week 21

Title

Tablet Usage After Sex

Description

These summaries represent counts and percentages of participants using tablet after last instance of vaginal sex.

Time Frame

Measured through Week 21

Title

Length of Time Vaginal Sexual Intercourse Took Place Before Using Tablet.

Description

Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given tablet was used after the encounter).

Time Frame

Measured through Week 21

Title

Gel Usage Before Sex

Description

These summaries represent counts and percentages of participants using gel before last instance of vaginal sex.

Time Frame

Measured through Week 21

Title

Length of Time Vaginal Sexual Intercourse Took Place After Using Gel.

Description

Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given gel was used before the encounter).

Time Frame

Measured through Week 21

Title

Gel Usage After Sex

Description

These summaries represent counts and percentages of participants using gel after last instance of vaginal sex.

Time Frame

Measured through Week 21

Title

Length of Time Vaginal Sexual Intercourse Took Place Before Using Gel.

Description

Median and inter-quartile range of the time between product usage and instance of vaginal intercourse (given gel was used after the encounter).

Time Frame

Measured through Week 21

Title

Reported Sharing of Product

Description

Time Frame

Measured through Week 21

Title

Grade 3 or Higher Toxicity for Systemic and Local Effects as Defined by the Protocol

Time Frame

Measured through Week 21

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Craig W. Hendrix, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Study Chair

Facility Information:

Facility Name

Alabama Microbicide CRS

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)

City

Bronx

State/Province

New York

Country

United States

Facility Name

Case CRS

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Pitt CRS

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213-2582

Country

United States

Facility Name

Botha's Hill CRS

City

Durban

State/Province

KwaZulu-Natal

Country

South Africa

Facility Name

Umkomaas CRS

City

Durban

State/Province

KwaZulu-Natal

Country

South Africa

Facility Name

Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS

City

Kampala

Country

Uganda

12. IPD Sharing Statement

Citations:

PubMed Identifier

17805450

Citation

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

Results Reference

background

PubMed Identifier

16470118

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.

Results Reference

background

PubMed Identifier

23383037

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.

Results Reference

result

PubMed Identifier

25969178

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.

Results Reference

derived

PubMed Identifier

23065145

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.

Results Reference

derived

Links:

URL

http://www.mtnstopshiv.org/

Description

Click here for the Microbicide Trials Network Web site

Learn more about this trial

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

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