Rectal Safety and Acceptability Study of Tenofovir 1% Gel

NCT01232803 | Completed Phase 1 DMC

• 2 other identifiers: MTN-0075U01AI068633-05
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 3

Brief Summary

MTN-007 is a Phase 1, randomized, blinded, placebo-controlled safety and acceptability study of vaginally formulated tenofovir 1% gel (a reduced-glycerin formulation), when applied rectally. The primary objective of this study is to assess the safety of vaginally formulated tenofovir 1% gel when applied rectally. After completing screening and baseline evaluation, eligible participants will be randomized to receive tenofovir 1% gel, 2% nonoxynol-9 gel (N-9) or placebo gel. The study will also include a no treatment arm. There will be 15 participants in each arm. Participants will return to the clinic, where they will self-administer a single dose of the study gel under observation. Within approximately 30 minutes, lavage, stool, and rectal biopsy specimens will be obtained. After a one-week recovery period, participants will return to the clinic for assessment. If no significant adverse events (AEs) are reported they will begin to self-administer once-daily outpatient doses of the study gel for 7 days. Participants will return to clinic for evaluation and specimen collection after completion of 7 days of daily dosing.

Conditions

Rectal Microbicides

Keywords

Rectal Microbicides; Tenofovir; Rectal use; Rectal mucosal damage

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of tenofovir 1% gel when applied rectally

  Grade 2 or higher AEs as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) and/or Addenda 1 and 3 (Female Genital and Rectal Grading Tables for Use in Microbicide Studies)

  Duration of Study

Secondary Outcomes (4)

• To evaluate the acceptability of tenofovir 1% gel when applied rectally

  Duration of Study

• To evaluate the safety of the placebo gel when applied rectally

  Duration of Study

• To determine whether use of tenofovir 1% gel is associated with rectal mucosal damage

  Duration of Study

• To determine whether use of 2% nonoxynol-9 gel (Gynol-II®) is associated with rectal mucosal damage

  Duration of Study

Study Arms (4)

2% N-9 gel

ACTIVE COMPARATOR

Rectal application of 2% N-9 gel

Drug: 2% N-9 gel

HEC placebo gel

PLACEBO COMPARATOR

Rectal application of HEC placebo gel

Drug: HEC Placebo gel

no-treatment arm

NO INTERVENTION

no intervention

Tenofovir 1% gel

EXPERIMENTAL

rectal application of Tenofovir 1% gel

Drug: Tenofovir 1% gel

Interventions

Tenofovir 1% gel DRUG

Entire contents of an applicator will be inserted rectally, for a total of 8 doses.

Tenofovir 1% gel

2% N-9 gel DRUG

Entire contents of an applicator will be inserted rectally, for a total of 8 doses.

2% N-9 gel

HEC Placebo gel DRUG

Entire contents of an applicator will be inserted rectally, for a total of 8 doses.

HEC placebo gel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ Age of 18 at screening, verified per site SOP
• Willing and able to provide written informed consent for screening and enrollment
• HIV-1 uninfected at screening
• Willing and able to communicate in English
• Willing and able to provide adequate locator information, as defined in site SOP
• Availability to return for all study visits, barring unforeseen circumstances
• Per participant report at screening, a history of consensual receptive anal intercourse (RAI) at least once in the prior year (Required to assure that participants have a context for the acceptability assessments).
• Willing to abstain from insertion of anything rectally, including sex toys, other than the study gel for the duration of study participation
• Willing to abstain from RAI for the duration of study participation
• Must agree to use study provided condoms for the duration of the study for vaginal and insertive anal intercourse
• Must be in general good health
• At Screening and Enrollment, must agree not to participate in other research studies involving drugs, medical devices, or genital products for the duration of study participation (until all follow-up visits are completed) In addition to the criteria listed above, female participants must meet the following criteria:
• Postmenopausal or using (or willing to use) an acceptable form of contraception (e.g., barrier method, intrauterine device (IUD), hormonal contraception, surgical sterilization, or vasectomization of male partner). If the female participant has female partners only, the method of contraception will be noted as a barrier method in the study documentation.

You may not qualify if:

• Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition
• At screening: participant-reported symptoms, and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current Centers for Disease Control (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or symptomatic genital warts requiring treatment. Note that an HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required Note: In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after screening visit will be allowed
• Anorectal sexually transmitted infections (STI) within six months prior to the Screening Visit
• At screening:
• Positive for hepatitis B surface antigen 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 For females: 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 (0.85 for female)/72 x (serum creatinine in mg/dL) For males: 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× the site laboratory upper limit of normal (ULN) Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \> 2.5× the site laboratory ULN
• +1 glucose or +1 protein on urinalysis (UA) History of bleeding problems
• History of significant gastrointestinal bleeding in the opinion of the investigator
• Allergy to methylparaben, propylparaben, sorbic acid, and components of N-9
• Known HIV-infected partners
• By participant report at enrollment, history of excessive daily alcohol use (as defined by the CDC as heavy drinking consisting of an average consumption of more than 2 drinks per day for men, and more than 1 drink per day for women), frequent binge drinking or illicit drug use that includes any injection drugs, methamphetamines (crystal meth), heroin, or cocaine including crack cocaine, within the past 12 months
• Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation: Heparin, including Lovenox® Warfarin Plavix® (clopidogrel bisulfate) Rectally administered medications (including over-the-counter products) Aspirin Non-steroidal anti-inflammatory drugs (NSAIDS) Any other drugs that are associated with increased likelihood of bleeding following mucosal biopsy
• By participant report at screening, use of post-exposure prophylaxis for HIV exposure, systemic immunomodulatory medications, rectally administered medications, rectally administered products (including condoms) containing N-9, or any investigational products within the 4 weeks prior to the Enrollment/Baseline Evaluation Visit and throughout study participation
• History of recurrent urticaria
• Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease In addition to the criteria listed above, female participants will be excluded if they meet any of the following criteria:
• Pregnant at the Enrollment/Baseline Visit

Sponsors & Collaborators

• CONRAD: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

The Fenway Institute

Boston, Massachusetts, 02115, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• McGowan I, Hoesley C, Cranston RD, Andrew P, Janocko L, Dai JY, Carballo-Dieguez A, Ayudhya RK, Piper J, Hladik F, Mayer K. A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007). PLoS One. 2013;8(4):e60147. doi: 10.1371/journal.pone.0060147. Epub 2013 Apr 3.

  PMID: 23573238 RESULT

• Leu CS, Mabragana M, Giguere R, Dolezal C, Carballo-Dieguez A, McGowan I. Use of a novel technology to track adherence to product use in a microbicide trial of short duration (MTN-007). AIDS Behav. 2013 Nov;17(9):3101-7. doi: 10.1007/s10461-013-0549-2.

  PMID: 23842718 RESULT

• Hladik F, Burgener A, Ballweber L, Gottardo R, Vojtech L, Fourati S, Dai JY, Cameron MJ, Strobl J, Hughes SM, Hoesley C, Andrew P, Johnson S, Piper J, Friend DR, Ball TB, Cranston RD, Mayer KH, McElrath MJ, McGowan I. Mucosal effects of tenofovir 1% gel. Elife. 2015 Feb 3;4:e04525. doi: 10.7554/eLife.04525.

  PMID: 25647729 RESULT

MeSH Terms

Interventions

Tenofovir; Gels

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2010
• First Posted: November 2, 2010
• Study Start: October 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 28, 2021

Record last verified: 2021-06

Locations

US (3)