A Phase 1 interventional study of dapivirine in HIV Infections, sponsored by International Partnership for Microbicides, Inc.. Completed at 1 site in South Africa. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-07-03.
Sponsored by International Partnership for Microbicides, Inc. · Phase 1, Interventional, and Prevention
A Phase I, Open-Label, Randomized, Crossover Trial to Investigate the Relative Bioavailability of the 25 mg Dapivirine Vaginal Ring-004 inserted every 30 days and 100 mg Dapivirine Vaginal Ring-008 inserted for 90 days in Healthy Female Participants
IPM 054 is a Phase I, open-label, randomized, crossover trial to determine the relative bioavailability in plasma and vaginal fluid of two formulations of the dapivirine vaginal ring in HIV-negative women. The trial will compare the dapivirine concentrations achieved in plasma and vaginal fluid over all timepoints for each 90-day use period in a two-period, two-sequence, crossover design.
Participants will be randomized to one of two treatment sequences (AB or BA). During two consecutive 90-day treatment periods, the participants will receive each of the following treatments according to their assigned treatment sequence. The treatment periods will be separated by a 28-day washout period.
Treatment Sequence 1:
Treatment Sequence 2:
Per participant report; using an effective method of contraception for at least 30 days (inclusive) prior to Enrolment, and intending to continue use of an effective method for the duration of trial participation; effective methods include:
Exclusion Criteria:
Pregnant at Screening or Enrolment or plans to become pregnant during the trial period* 2) Diagnosed with a urinary tract infection (UTI) or reproductive tract infection (RTI) at Screening or Enrolment based on clinical assessment* 3) Diagnosed with an acute sexually transmitted infection (STI) requiring treatment per current local guidelines at Screening such as gonorrhoea (GC), chlamydia trachomatis (CT), trichomonas, and/or syphilis* 4) Has an abnormal cytology finding at screening or clinically apparent Grade 1 or higher pelvic examination finding (observed by trial staff) at Screening or Enrolment, as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017, and/or Addendum (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])* 5) Participant report and/or clinical evidence of any of the following:*
Participation in any other research trial involving drugs, medical devices, vaginal products or vaccines, in the 60 days prior to Enrolment 6) Completed use of oral pre-exposure prophylaxis (PrEP) for HIV prevention and/or post-exposure prophylaxis (PEP) for potential HIV exposure within one month prior to screening, and/or anticipated use and/or unwillingness to abstain from PrEP during trial participation 7) Has any Grade 1 or higher laboratory abnormalities at the Screening Visit 8) Participant has a positive test for Hepatitis B surface antigen (HBsAg) or is Hepatitis C virus antibody (HCV-Ab) positive 9) Participant has a positive urine drug test or a positive alcohol breath test.
25 mg dapivirine vaginal ring (Ring-004) for 90 days (replaced every 30 days) (Treatment A), followed by the 100 mg dapivirine ring (Ring-008) used continuously for 90 days (Treatment B)
Drug: dapivirine
100 mg dapivirine vaginal ring (Ring-008) used continuously for 90 days (Treatment B), followed by the 25 mg dapivirine ring (Ring-004) for 90 days (replaced every 30 days) (Treatment A)
Drug: dapivirine
dapivirine vaginal ring
To determine the relative bioavailability of Dapivirine Vaginal Ring-008 compared to Dapivirine Vaginal Ring-004 by comparison of dapivirine plasma pharmacokinetic parameters.
Dapivirine concentrations in plasma, measured at specified timepoints during each 90-day ring use period.
Time frame: during a 90 day use period
To further characterize the pharmacokinetic profile of Dapivirine Vaginal Ring-008 compared to Dapivirine Vaginal Ring-004 in vaginal fluid
Dapivirine concentrations in vaginal fluid, measured at specified timepoints during each 90-day ring use period, and for 1 day following ring removal. Vaginal fluid samples will be collected using tear test strips at the location of the cervix.
Time frame: during each 90 days ring use period
To evaluate the incidence of Grade 1 or higher genitourinary treatment-emergent adverse events and the incidence of Grade 3 or higher treatment-emergent adverse events of the two dapivirine vaginal ring formulations used continuously for 90 days
Evaluating the incidence of treatment-emergent adverse events with severity grades as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies \[Dated November 2007\]).
Time frame: during each 90 days ring use period
To assess the effects on vaginal flora when using Dapivirine Vaginal Ring-004 and Dapivirine Vaginal Ring-008 formulations used continuously for 90 days
Assessing the effects by evaluating changes in vaginal pH from baseline and the incidence of bacterial vaginosis, assessed by Nugent scores of ≥ 7, determined from vaginal specimens collected for Gram staining.
Time frame: during each 90 days ring use period
To characterize the vaginal microenvironment over the course 90 days of ring use.
The amount of dapivirine released over three 30-day periods (ie, 90 days) for Ring-004 and over 90 days for Ring-008. Residual dapivirine levels in used rings
Time frame: during a 90 day use period
Plan to share: No
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International Partnership for Microbicides, Inc.