Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults
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|ClinicalTrials.gov Identifier: NCT03239483|
Recruitment Status : Completed
First Posted : August 4, 2017
Results First Posted : November 7, 2019
Last Update Posted : November 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections||Drug: Dapivirine gel Drug: Placebo gel||Phase 1|
This study will evaluate the safety and pharmacokinetics (PK) of dapivirine gel (0.05%) administered rectally to HIV-1 seronegative adults.
Participants will be randomized to receive a single dose of either rectally administered dapivirine gel (0.05%) or placebo gel at study entry (Day 0). Following a minimum 2-week washout period, participants or study staff will administer daily rectal doses of the assigned gel for 7 consecutive days under direct observation in the clinic.
Participants will be in the study for approximately 40 days, and they will attend 16 study visits. Study visits may include behavioral assessments, physical examinations, blood and urine collection, and pelvic and anorectal sample collection. Some visits will include intensive PK sampling. Study staff will contact participants 1 week after Visit 16 for follow-up safety monitoring.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||28 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double Blind, Placebo-Controlled, Phase 1 Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults|
|Actual Study Start Date :||October 26, 2017|
|Actual Primary Completion Date :||September 20, 2018|
|Actual Study Completion Date :||September 20, 2018|
Experimental: Dapivirine gel
Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.
Drug: Dapivirine gel
Dapivirine gel (0.05%); administered rectally
Placebo Comparator: Placebo gel
Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.
Drug: Placebo gel
Universal HEC placebo gel; administered rectally
- Frequency of Grade 2 or Higher Adverse Events (AEs) [ Time Frame: Measured after the participant has started study product until the participant's study termination at approximately Day 40 ]As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital [Dated November 2007], Male Genital [Dated November 2007] and Rectal [Clarification Dated May 2012] Grading Tables for Use in Microbicide Studies)
- Measurement of Dapivirine Concentrations in Plasma [ Time Frame: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, before last dose and 1,2, 24,48, and 72 hours after last dose. ]As assessed by pharmacokinetic sampling and analysis
- Measurement of Dapivirine Concentrations in Rectal Fluid [ Time Frame: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, and 1,2, 24,48, and 72 hours after last dose. ]As assessed by pharmacokinetic rectal fluid sampling and analysis
- Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates [ Time Frame: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose and 1,2, 24,48, and 72 hours after last dose. ]As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis
- Terminal Half-life of Dapivirine Concentrations in Plasma [ Time Frame: From samples collected 24 hours after first dose to 72 hours after last daily dose ]The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.
- Acceptability: Ease of Use [ Time Frame: after completing the study (study day 40) ]The number of participants who responded by questionnaire that the study product was easy or very easy to use.
- Acceptability: Comfort [ Time Frame: after completing the study (study day 40) ]The number of participants who responded on a questionnaire that the study product was comfortable or very comfortable.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03239483
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, Pennsylvania|
|University of Pittsburgh CRS|
|Pittsburgh, Pennsylvania, United States, 15213|
|Silom Community Clinic CRS|
|Nonthaburi, Bangkok, Thailand, 11000|
|Study Chair:||Ross D. Cranston, MD, FRCP||Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias I Pujol|