Rectal Safety and Acceptability Study of Tenofovir 1% Gel
Information source: CONRAD
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Rectal Microbicides
Intervention: Tenofovir 1% gel (Drug); 2% N-9 gel (Drug); HEC Placebo gel (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: CONRAD
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.
Clinical Details
Official title: A Phase 1 Randomized, Double-Blinded, Placebo-Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)
Primary outcome: To evaluate the safety of tenofovir 1% gel when applied rectally
Secondary outcome: To evaluate the acceptability of tenofovir 1% gel when applied rectallyTo evaluate the safety of the placebo gel when applied rectally To determine whether use of tenofovir 1% gel is associated with rectal mucosal damage To determine whether use of 2% nonoxynol-9 gel (Gynol-II®) is associated with rectal mucosal damage
Detailed description:
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. This study will also determine whether
rectal use of tenofovir 1% gel is associated with rectal mucosal damage using a broad range
of immunological safety biomarkers, utilizing N-9 as a positive control, as rectal
application of N-9 is known to cause mild but transient mucosal damage. Other secondary
objectives include evaluations of the acceptability of rectal administration of tenofovir 1%
gel as well as the safety of HEC placebo gel when applied rectally.
Participants will be randomized to receive a single dose of tenofovir 1% gel, 2% N-9 gel or
a placebo gel that is applied by a clinician at the study site. 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 the clinic for evaluation and specimen collection after completion of 7 days of
daily dosing.
Receptive anal intercourse is common among men who have sex with men and there is increasing
evidence that heterosexual women in the developed and developing world also practice anal
sex. It can therefore be anticipated that once vaginal microbicides are licensed, they will
be used in both the vaginal and rectal compartments. As a consequence, there is a need to
evaluate both the rectal and vaginal safety profile of candidate microbicides. The Rectal
Microbicide Program clinical protocols have therefore been developed to assess the safety
and pharmacology of tenofovir 1% gel when used rectally in men and women as well as address
critical questions regarding rectal microbicides through exploratory objectives.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. ≥ Age of 18 at screening, verified per site SOP
2. Willing and able to provide written informed consent for screening and enrollment
3. HIV-1 uninfected at screening
4. Willing and able to communicate in English
5. Willing and able to provide adequate locator information, as defined in site SOP
6. Availability to return for all study visits, barring unforeseen circumstances
7. Per participant report at screening, a history of consensual RAI at least once in the
prior year (Required to assure that participants have a context for the acceptability
assessments).
8. Willing to abstain from insertion of anything rectally, including sex toys, other
than the study gel for the duration of study participation
9. Willing to abstain from RAI for the duration of study participation
10. Must agree to use study provided condoms for the duration of the study for vaginal
and insertive anal intercourse
11. Must be in general good health
12. 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:
13. Postmenopausal or using (or willing to use) an acceptable form of contraception
(e. g., barrier method, 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.
Exclusion Criteria:
1. 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
2. At screening: participant-reported symptoms, and/or clinical or laboratory diagnosis
of active rectal or reproductive tract infection requiring treatment per current 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 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
3. Anorectal STI within six months prior to the Screening Visit
4. 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
5. History of significant gastrointestinal bleeding in the opinion of the investigator
6. Allergy to methylparaben, propylparaben, sorbic acid, and components of N-9
7. Known HIV-infected partners
8. 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
9. 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
10. 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
11. History of recurrent urticaria
12. 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:
13. Pregnant at the Enrollment/Baseline Visit
14. Breastfeeding at screening or intend to breastfeed during study participation per
participant report.
Locations and Contacts
University of Alabama at Birmingham, Birmingham, Alabama 35294, United States
The Fenway Institute, Boston, Massachusetts 02115, United States
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States
Additional Information
Starting date: October 2010
Last updated: March 19, 2013
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