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Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by CONRAD
Sponsor:
Collaborators:
Information provided by (Responsible Party):
CONRAD
ClinicalTrials.gov Identifier:
NCT01687218
First received: August 27, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

MTN-017 is a Phase 2, multi-site, randomized, six-sequence, two three-period, open label crossover study, examining the effects of oral Truvada and reduced glycerin 1% tenofovir gel. The study population will be sexually active, HIV-uninfected males who are 18 years of age or older, who report a history of receptive anal intercourse in the past 3 months. Each of the study product regimens offers different advantages to participants seeking an effective HIV prevention agent. How these relative advantages will compare in terms of safety, acceptability, systemic and local absorption, and adherence will be examined within this study.


Condition Intervention Phase
HIV
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet)
Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel)
Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Phase 2 Randomized Sequence Open Label Expanded Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel

Resource links provided by NLM:


Further study details as provided by CONRAD:

Primary Outcome Measures:
  • Saftey Profiling [ Designated as safety issue: Yes ]
    Compare the safety profiles of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel

  • Acceptability [ Designated as safety issue: No ]
    To evaluate and compare acceptability of daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel


Secondary Outcome Measures:
  • Pharmacokinetics [ Designated as safety issue: No ]
    To compare systemic and local PK among daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel

  • Adherence [ Designated as safety issue: No ]
    To evaluate and compare adherence to daily FTC/TDF tablet, daily TFV RG 1% gel, and RAI-associated TFV RG 1% gel


Other Outcome Measures:
  • Pharmacodynamics [ Designated as safety issue: No ]
    To characterize pharmacodynamic responses following oral and rectal exposure to antiretroviral drugs

  • Mucosal immunity [ Designated as safety issue: No ]
    To characterize changes in mucosal immunity between baseline and the end of the daily FTC/TDF and TFV RG 1% gel product use

  • Correlation between PK and adherence [ Designated as safety issue: No ]
    To assess correlation of PK with adherence measures

  • Factors associated with adherence [ Designated as safety issue: No ]
    To identify factors associated with product adherence and whether they differ by product used (FTC/TDF or TFV RG 1% gel) or regimen (daily use or RAI-associated use)

  • Sexual activity and condom use [ Designated as safety issue: No ]
    To examine whether sexual activity or condom use varies by product used

  • Product sharing [ Designated as safety issue: No ]
    To determine the level of sharing of study products with non-participants and to assess with whom products are shared

  • Problem practices [ Designated as safety issue: No ]
    To determine the prevalence of behavioral practices associated with anal intercourse that may affect microbicide use


Estimated Enrollment: 186
Study Start Date: June 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Active Comparator: Group 2
Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Active Comparator: Group 3
Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Active Comparator: Group 4
Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Active Comparator: Group 5
Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks); followed by Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks)
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)
Active Comparator: Group 6
Receptive Anal Intercourse Associated Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks);followed by Daily Rectally-Applied Tenofovir Reduced Glycerin 1% Gel (8 weeks); followed by Daily Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet (8 weeks)
Drug: Oral FTC/TDF (Daily Emtricitabine/Tenofovir Disoproxil fumarate Tablet) Drug: Rectal Daily TFV RG 1% gel (Rectally applied Tenofovir Reduced Glycerin 1% Gel) Drug: Rectal RAI-associated TFV RG 1% gel (Receptive Anal Intercourse Associated rectally applied Tenofovir Reduced Glycerin 1% Gel)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or transgender female > age of 18 at Screening
  2. Able and willing to provide written informed consent
  3. HIV-1 uninfected at Screening and Enrollment
  4. Able and willing to provide adequate locator information, as defined in site SOP
  5. Available to return for all study visits, barring unforeseen circumstances and willing to comply with study participation requirements
  6. In general good health at Screening and Enrollment, as determined by the site IoR or designee
  7. Per participant report, a history of consensual RAI at least once in the past 3 months
  8. Per participant report at Screening and Enrollment, agrees not to engage in receptive or insertive sexual activity with another study participant for the duration of study participation.
  9. Willing to use study-provided condoms for the duration of the study for penetrative intercourse
  10. Willing to not take part in other research studies involving drugs, medical devices, vaccines or genital products for the duration of study participation (including the time between Screening and Enrollment)
  11. Men and transgender females who agree to take part in the PK, PD and Mucosal Immunology Subset, must also agree to abstain from:

    • Inserting anything into the rectum, including abstaining from RAI for 72 hours after the collection of biopsies
    • Taking non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and/or other drugs that are associated with increased likelihood of bleeding following mucosal biopsy collection for 72 hours prior to and following the collection of biopsies.

Exclusion Criteria:

  1. At Screening, participant-reported symptoms, and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection requiring treatment per current World Health Organization (WHO) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic Chlamydia trachomatis (CT) infection, Neisseria gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts.

    Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required.

    In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after the screening visit will be allowed

  2. History of inflammatory bowel disease as reported by participant history
  3. At Screening:

    • Positive for hepatitis B surface antigen
    • Positive for hepatitis C antibody
    • Hemoglobin < 10.0 g/dL
    • Platelet count less than 100,000/mm3
    • White blood cell count < 2,000 cells/mm3 or > 15,000 cells/mm3
    • Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL)
    • Serum creatinine > 1.3 x the site laboratory upper limit of normal (ULN)
    • Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5× the site laboratory ULN
    • PK, PD and Immunological Subset only: International normalized ratio (INR) > 1.5× the site laboratory ULN or partial thromboplastin time (PTT) > 1.25× the site laboratory ULN
  4. Known allergy to methylparaben and/or propylparaben
  5. Known allergy to any of the study products.
  6. Per participant report, use of the following medications and/or products within 12 weeks prior to screening, and/or anticipated use or unwillingness to abstain from use throughout study participation:

    • Any investigational products
    • Systemic immunomodulatory medications
    • Use of Heparin, including Lovenox®
    • Warfarin
    • Plavix® (clopidogrel bisulfate)
    • Rectally-administered medications or products, containing N-9 or corticosteroids
  7. By participant report, use of post-exposure prophylaxis (PEP) for HIV exposure within the 12 weeks prior to screening or anticipated use during study participation.
  8. Symptoms suggestive of acute HIV seroconversion at Screening and Enrollment
  9. Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives would make the patient unsuitable for the study or unable/unwilling to comply with the study requirements. Such conditions may include, but are not limited to, colorectal abnormalities, substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological or psychiatric disease.
  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: NCT01687218

Contacts
Contact: Ross D. Cranston, MD, FRCP 412-383-2054 rdc27@pitt.edu

Locations
United States, California
HIV Research Section, San Francisco - Department of Public Health Recruiting
San Francisco, California, United States, 94102
Contact: Albert Liu, MD, MPH    415-554-9104    albert.liu@sfdph.org   
Principal Investigator: Albert Liu, MD, MPH         
United States, Massachusetts
The Fenway Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Kenneth Mayer, MD    617-927-6400    Kenneth_Mayer@brown.edu   
Principal Investigator: Kenneth Mayer, MD         
United States, Pennsylvania
University of Pittsburgh Medical Center (UPMC) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Ross D. Cranston, MD, FRCP    412-383-2054    rdc27@pitt.edu   
Principal Investigator: Ross D. Cranston, MD, FRCP         
Peru
IMPACTA Recruiting
Lima, Peru
Contact: Pedro Gonzalez, MD, MAS    51-1- 562-1600 ext 103    pgonzales@impactaperu.org   
Principal Investigator: Pedro Gonzales, MD, MAS         
Puerto Rico
University of Puerto Rico Medical Sciences Campus - Maternal Infant Studies Center (CEMI) Recruiting
San Juan, Puerto Rico, 00936-5067
Contact: Carmen D Zorrilla, MD    787-753-5913    carmen.zorrilla@upr.edu   
Principal Investigator: Carmen D Zorrilla, MD         
South Africa
Desmond Tutu HIV Foundation Recruiting
Cape Town, South Africa
Contact: Linda Bekker    27216506959    Linda-gail.bekker@hiv-research.org.za   
Principal Investigator: Linda Bekker         
Thailand
Research Institute for Health Sciences - Chiang Mai University Recruiting
Chiang Mai, Thailand, 50202
Contact: Suwat Chariyalertsak, MD, Dr.PH    66 53 945055    suwat.c@cmu.ac.th   
Principal Investigator: Suwat Chariyalertsak, MD, Dr.PH         
Thailand MOPH - US CDC Collaboration (TUC) Not yet recruiting
Nonthaburi, Thailand, 11000
Contact: Timothy H. Holtz, MD, MPH, FACP    66-2-580-0669 ext 456    tholtz@th.cdc.gov   
Principal Investigator: Timothy H. Holtz, MD, MPH, FACP         
Sponsors and Collaborators
CONRAD
Investigators
Study Chair: Ross D. Cranston, MD, FRCP University of Pittsburgh Medical Center (UPMC)
Study Chair: Javier R. Lama, MD, MPH Asociacion Civil Impacta Salud y Educacion (IMPACTA)
  More Information

No publications provided

Responsible Party: CONRAD
ClinicalTrials.gov Identifier: NCT01687218     History of Changes
Other Study ID Numbers: MTN-017, UM1AI068633, 11857
Study First Received: August 27, 2012
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Emtricitabine
Glycerol
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Cryoprotective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014