Pharmacokinetic Study of Dapivirine Gel Administered Rectally to HIV-1 Seronegative Adults

NCT03393468 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MTN-03312065
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of dapivirine gel administered rectally to HIV-1 seronegative adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (3)

• Measurement of dapivirine concentrations in rectal fluid

  As assessed by pharmacokinetic sampling and analysis

  Measured through approximately 1 month

• Measurement of dapivirine concentrations in plasma

  As assessed by pharmacokinetic sampling and analysis

  Measured through approximately 1 month

• Measurement of dapivirine concentrations in rectal mucosal tissue homogenates

  As assessed by pharmacokinetic sampling and analysis

  Measured through approximately 1 month

Secondary Outcomes (1)

• Frequency of Grade 2 or higher adverse events (AEs)

  Measured through approximately 1 month

Study Arms (2)

Sequence A: Dapivirine gel

EXPERIMENTAL

Participants will receive 2.5 g of dapivirine gel administered rectally via an applicator, followed by a 2- to 4-week washout period. Participants will then receive a second dose of up to 10 g of dapivirine gel administered rectally via a coital simulation device.

Drug: Dapivirine gel

Sequence B: Dapivirine gel

EXPERIMENTAL

Participants will receive up to 10 g of dapivirine gel administered rectally via a coital simulation device, followed by a 2- to 4-week washout period. Participants will then receive a second dose of 2.5 g of dapivirine gel administered rectally via an applicator.

Drug: Dapivirine gel

Interventions

Dapivirine gel DRUG

Dapivirine gel (0.05%); administered rectally

Sequence A: Dapivirine gel; Sequence B: Dapivirine gel

Eligibility Criteria

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

You may qualify if:

• Men and transgender women who are 18 years or older at Screening, verified per site standard operating procedure (SOP)
• Able and willing to provide written informed consent
• HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II of the study protocol and willing to receive HIV test results
• Able and willing to provide adequate locator information, as defined in site SOP
• Available to return for all study visits and willing to comply with study participation requirements
• In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee
• At Screening, history of consensual receptive anal intercourse (RAI) at least once in the past year per participant report
• Willing not to take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation (including the time between Screening and Enrollment)
• Willing to abstain from RAI, receptive oral anal stimulation (i.e., rimming), rectal stimulation via fingers, as well as the insertion of any non-study products into the rectum for 72 hours before and after each study visit

You may not qualify if:

• At Screening:
• Hemoglobin Grade 1 or higher\*
• Platelet count Grade 1 or higher\*
• White blood count Grade 2 or higher\*
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher\*
• Serum creatinine greater than 1.3 times the site laboratory upper limit of normal (ULN)
• International normalized ratio (INR) greater than 1.5 times the site laboratory ULN
• Positive for hepatitis C antibody
• Positive for hepatitis B surface antigen
• History of inflammatory bowel disease by participant report
• (\*As per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017)
• Known adverse reaction to latex or polyurethane (ever)
• Anticipated use of and/or unwillingness to abstain from the following medications during study participation:
• Anticoagulant medications
• Aspirin (greater than 81 mg/day)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Ken Ho, MD

  University of Pittsburgh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 8, 2018
• Study Start: May 10, 2018
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: October 25, 2021

Record last verified: 2019-10

Locations

US (1)