Clinical trial NCT01277640: Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures
Official title: Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Topical Penile Exposures
Keywords: male tolerance
HIV-1
microbicide
dapivirine
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2011-01-17
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the safety of male genitalia when exposed to dapivirine gel following seven once daily applications.


Eligibility criteria: Inclusion Criteria:

* At least 18 years of age at Screening, verified per site standard operating procedure (SOP)
* Able and willing to provide written informed consent to be screened for and take part in the study
* At Screening, able and willing to provide adequate locator information, as defined per site SOP
* Able and willing to communicate in written and spoken English
* HIV-uninfected at Screening per Algorithm in Appendix II
* In general good health, according to the clinical judgment of the Investigator of Record (IoR) or designee
* Willing to abstain from vaginal, oral and anal intercourse (including receptive anal intercourse), even with a condom; masturbation, and other activities that may cause irritation or injury to the penis during study participation
* Willing to abstain from using any genitally-applied preparations (except use of usual cleansing products for genital hygiene) other than the study product during study participation
* Willing to abstain from non-urgent surgical procedures of the penis/GU area for the duration of study participation (e.g. circumcision)
* At Screening and Enrollment, agrees 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)

Exclusion Criteria:

* Participant report of any of the following:

  * Known adverse reaction to any of the study products or components of the study products (ever)
  * Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to Enrollment
  * Penile procedures (e.g. biopsy, circumcision) within 42 days or less prior to Enrollment
  * Participation in any other research study involving drugs, medical devices, or genital products within 30 days or less prior to Enrollment
  * Within the three months prior to Enrollment, history of a non-gonococcal urethritis and/or sexually transmitted infection (STI), including outbreak of genital herpes or condylomata
  * For uncircumcised men, the treatment of candidal balanoposthitis/ balanitis within 30 days prior to Enrollment
  * History of recurrent dermatosis (e.g. eczema)
  * Non-therapeutic injection drug use in the 12 months prior to Screening
  * Currently using an immunosuppressant (with the exception of local nongenital use of low potency products e.g. inhaled corticosteroid for asthma)
  * Has any of the following laboratory abnormalities at Screening:

    * Hemoglobin \< 10.0 g/dL
    * Platelet count \< 100,000/mm3
    * White blood cell count \< 2,000 cells/mm3
    * Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \> 2.5x the site laboratory upper limit of normal (ULN)
    * Serum creatinine \> 1.3x the site laboratory ULN
    * Calculated creatinine clearance less than 80 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140-age in years) x (weight in kg) x 0.85/72 x serum creatinine in mg/dL Note: Otherwise eligible participants with any of the above exclusionary laboratory results may be re-tested. If a participant is re-tested and a non exclusionary result is documented within 30 days of providing informed consent for Screening, the participant may be enrolled.
* At Screening or Enrollment, diagnosed with STI or reproductive tract infection (RTI) requiring treatment, per current Centers for Disease Control and Prevention (CDC) guidelines
* At Screening or Enrollment, has a clinically apparent Grade 1 or higher genital exam finding (observed by study staff)
* At Screening or Enrollment, has Grade 1 or higher genital or urinary symptoms
* At Screening or Enrollment, diagnosed with phimosis or hypospadias
* At Screening or Enrollment, penile, scrotal piercing or penile tattoos observed during genital examination
* 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

Primary outcomes:
measure: To determine the genitourinary safety of dapivirine gel (0.05%), the endpoint was the proportion of men subjected to dapivirine gel or placebo gel experiencing specific, protocol-defined safety events during the study (see description).
timeFrame: 8 days
Secondary outcomes:
measure: To assess the pharmacokinetics in plasma following 7 days of once daily penile application of dapivirine gel (0.05%)
timeFrame: 8 days
measure: To assess the systemic safety following 7 days of once daily penile application of dapivirine gel (0.05%)
timeFrame: 8 days
measure: To assess the acceptability following 7 days of once daily penile application of dapivirine gel (0.05%)
timeFrame: 8 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Division of Infectious Diseases, University of Pittsburgh Medical Center
name: Ross D. Cranston, MD, FRCP
role: STUDY_CHAIR
References:
citation: Cranston RD, Hoesley C, Carballo-Dieguez A, Hendrix CW, Husnik M, Levy L, Hall W, Soto-Torres L, Nel AM. A randomized male tolerance study of dapivirine gel following multiple topical penile exposures (MTN 012/IPM 010). AIDS Res Hum Retroviruses. 2014 Feb;30(2):184-9. doi: 10.1089/AID.2013.0170. Epub 2013 Oct 26.