Phase 1
Completed N=28
Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults
Source: ClinicalTrials.gov NCT03239483 ↗Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Nov 2019
Primary outcomePrimary: Frequency of Grade 2 or Higher Adverse Events (AEs) — 3; 5 Participants — p=0.072
Summary
The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of dapivirine gel (0.05%) administered rectally to HIV-1 seronegative adults.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Frequency of Grade 2 or Higher Adverse Events (AEs) |
3; 5 | 0.072 |
| PRIMARY Measurement of Dapivirine Concentrations in Plasma |
31.5; 326; 20.1; 0; 0; 67.9 | — |
| PRIMARY Measurement of Dapivirine Concentrations in Rectal Fluid |
30.1; 12.765; 0; 0.009; 0; 0.180 | — |
| PRIMARY Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates |
0.256; 0; 0; 0; 0; 0 | — |
| PRIMARY Terminal Half-life of Dapivirine Concentrations in Plasma |
52.6 | — |
| SECONDARY Acceptability: Ease of Use |
16; 9 | 1.00 |
| SECONDARY Acceptability: Comfort |
15; 7 | 0.591 |
Eligibility Criteria
Inclusion Criteria
- Age of 18 - 45 years (inclusive) 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 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
- Per participant report, a history of consensual receptive anal intercourse (RAI) at least once in the past calendar year
- Willing to not 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 be sexually abstinent for 72 hours prior to each study visit, during the study product use periods and for 72 hours after biopsy collection. Note: See Criteria 12 and 13 for additional restrictions for female participants
- Willing to abstain from inserting any non-study products into the rectum for 72 hours prior to each study visit and during the study product use periods. Note: See Criteria 12 and 13 for additional restrictions for female participants
Females must also meet the following additional inclusion criteria to be eligible for study inclusion:
- Women over the age of 21 (inclusive) must have documentation of a satisfactory Pap within the past 3 years prior to Enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (dated November 2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result
- Willing to be sexually abstinent for 72 hours prior to each study visit and during the study product use periods and for 7 days after biopsy collection
- Willing to abstain from inserting any non-study products into the vagina for 72 hours prior to each study visit, during the study product use periods and for 7 days after biopsy collection
- Willing to use an effective method of contraception for at least 30 days (inclusive) prior to Enrollment and intending to continue use of an effective method for the duration of study participation; effective methods include: hormonal methods (except contraceptive ring), intrauterine device (IUD), sterilization (of participant and/or partner, as defined in site SOPs), or sexually abstinent for 90 days prior to Screening
Exclusion Criteria
- At Screening:
- Hemoglobin Grade 1 or higher*
- Platelet count Grade 1 or higher*
- White blood count Grade 2 or higher*
- Serum creatinine greater than 1.3× the site laboratory upper limit of normal (ULN)
- International normalized ratio (INR) greater than 1.5× the site laboratory ULN
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher*
- 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
- Note: Otherwise eligible participants with an exclusionary test result (other than HIV, HBV or HCV) can be re-tested during the screening process. If a participant is re-tested and a non-exclusionary result is documented within 45 days of providing informed consent for screening, the participant may be enrolled.
- Anticipated use of and/or unwillingness to abstain from the following medications during study participation:
- Heparin, including Lovenox®
- Warfarin
- Plavix® (clopidogrel bisulfate)
- Aspirin (greater than 81 mg)
- Non-steroidal anti-in
Data sourced from ClinicalTrials.gov (NCT03239483). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.