A Double-Blind, Randomised, Placebo-Controlled Pharmacokinetic and Safety Trial in Healthy HIV-Negative Women to Assess the Delivery of Dapivirine From a Matrix Vaginal Ring and to Evaluate the Safety of a Matrix Vaginal Ring Containing 25 MG of Dapivirine
Overview
- Phase
- Phase 1
- Intervention
- dapivirine
- Conditions
- HIV Infections
- Sponsor
- International Partnership for Microbicides, Inc.
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Safety: To assess the safety of the dapivirine vaginal ring, the endpoint was the proportion of women in four vaginal ring regimens on dapivirine or placebo ring experiencing specific, protocol-defined safety events during the study (see description)
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
The proposed study is a single-center, double-blind, randomised, placebo-controlled trial to evaluate the delivery of dapivirine from matrix vaginal rings over a 56 and 57 day period and to assess the safety as compared to placebo vaginal rings in 48 healthy, HIV-negative, sexually active women.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Women ≥18 and ≤40 years of age who can give written informed consent;
- •Available for all visits and consent to follow all procedures scheduled for the trial;
- •Healthy and self-reported sexually active (defined as an average of one penetrative penile vaginal coital act per month for the 3 months prior to enrolment);
- •Be on a stable form of contraception, defined as:
- •A stable oral contraceptive regimen for at least 2 months prior to enrolment, OR,
- •Transdermal contraceptive patch for at least 3 months prior to enrolment, OR,
- •Long-acting progestins for at least 6 months prior to enrolment, OR,
- •An IUD inserted (with no vaginal or gynaecological complaints associated with its use) at least 3 months prior to enrolment, OR,
- •Have undergone surgical sterilization at least 3 months prior to enrolment;
- •In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle, defined as having a minimum of 21 days and a maximum of 35 days between menses;
Exclusion Criteria
- •Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening;
- •Currently breast-feeding;
- •Currently or within two months of participation in any other clinical research trial involving investigational or marketed products prior to screening;
- •Untreated symptomatic urogenital infections, e.g., urinary tract or other sexually transmitted infections, or other gynaecological conditions such as vaginal itching, pain, or discharge, within 2 weeks prior to enrolment;
- •Presence of any abnormal clinically significant physical finding on the vulva, vaginal walls or cervix during pelvic examination and/or colposcopy at pre-enrolment;
- •History of urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence;
- •Current vulvar or vaginal symptoms / abnormalities that could influence the trial results;
- •Pap test result that requires cryotherapy, biopsy, treatment (other than for infection); or further evaluation \[this includes any findings of atypical squamous cells of undetermined significance (ASCUS)\];
- •Symptomatic genital HSV infection or a history of genital herpetic infection;
- •Any Grade 2, 3 or 4 haematology, chemistry or urinalysis laboratory abnormality at baseline (screening) according to the DAIDS Table for Grading Adverse Events (NOTE: This table can be found at: http://rcc.tech-res.com/safetyandpharmacovigilance;and a standardized version will be provided to the research centre in the Study Operations Manual);
Arms & Interventions
Group A1: Dapivirine Vaginal Ring
Intervention: dapivirine
Group A2: Placebo Vaginal Ring
Intervention: placebo
Group B1: Dapivirine Vaginal Ring
Intervention: dapivirine
Group B2: Placebo Vaginal Ring
Intervention: placebo
Outcomes
Primary Outcomes
Safety: To assess the safety of the dapivirine vaginal ring, the endpoint was the proportion of women in four vaginal ring regimens on dapivirine or placebo ring experiencing specific, protocol-defined safety events during the study (see description)
Time Frame: 56/57 days
* Mucosal abnormalities (as defined in the CONRAD/WHO manual) visible during naked eye examination and/or colposcopy; * Abnormal vaginal pH and/or abnormal vaginal flora during the course of the trial. * Positive diagnostic tests for trichomonas, gonorrhoea and/or chlamydia; * At least one adverse event during the 12-week trial period; * Any laboratory abnormalities on haematology, electrolytes, liver function, and renal function.
Pharmacokinetics: To examine local and systemic pharmacokinetics of dapivirine concentrations delivered by the vaginal rings, measured in plasma, vaginal fluids and cervical tissue during the trial period
Time Frame: 56/57 days