A Phase I Pharmacokinetics and Safety Study of Two Dapivirine Intravaginal Gels

A Double-Blind, Randomized, Placebo-Controlled Phase I Study to Compare the Pharmacokinetics of Intravaginal Dapivirine Gel 4750, 0.05%, 2.5g and Dapivirine Gel 4789, 0.05%, 2.5g Formulations and to Assess the Safety as Compared to the Intravaginal HEC-Based Universal Placebo Gel, 2.5g in Healthy HIV-Negative Women.

IPM 012 is a double-blind, randomized, placebo-controlled phase I study conducted at one research center in Belgium among 36 healthy, HIV-negative women of 18-40 years of age, randomized in a 1:1:1 ratio to assess plasma, vaginal fluid and vaginal tissue levels and the pharmacokinetics of dapivirine when applying either Dapivirine Gel 4750, 0.05%, 2.5g or Dapivirine Gel 4789, 0.05%, 2.5g intravaginally for 11 days (1 day followed by a 3 day washout period and then 10 consecutive days); and to assess the safety of these gels as compared to the intravaginal HEC-based universal placebo gel.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Dapivirine Gel 4750, 0.05%, 2.5g; Drug: Dapivirine Gel 4789, 0.05%, 2.5g; Drug: HEC-based Placebo Gel

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, B-2060
    • SGS Life Science Services Research Unit Stuivenberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women between 18 and 40 years of age, inclusive
• Willing and able to give written informed consent
• Available for all visits and consent to follow all procedures
• Healthy, based on medical history, vital signs, physical examination, urinalysis, laboratory evaluations for genital infections and laboratory evaluations for hematology, liver and renal function
• HIV-negative as determined by a HIV-1 ELISA test at enrollment
• Willing to abstain from sexual activity for the duration of the study
• On stable oral contraceptive regimen for 2 months prior to enrollment and willing to continue
• Upon pelvic/speculum examination, the cervix and vagina appear normal
• Willing to refrain from the use of vaginal products from 14 days prior to enrollment and for the duration of the study

Exclusion Criteria:

• History of alcoholism, drug abuse, psychosis, antagonistic personality, poor motivation or other emotional or intellectual problems that are likely to invalidate the informed consent process or adversely impact adherence with protocol requirements
• History of sensitivity/allergy to any component of the study product or to latex
• Currently pregnant or breast-feeing, or within 3 months of last pregnancy outcome
• Currently or within one month of participating in any other clinical research study
• History or current diagnosis and/or treatment for a STD within the last three months prior to enrollment
• Current vulvar, vaginal or cervical symptoms/abnormalities as determined by pelvic/speculum exam or colposcopy that could influence the study results
• History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding or urethral obstruction within the last 3 months
• Current non-iatrogenic pelvic/colposcopic exam findings involving deep epithelial disruption
• Smoking more than 10 cigarettes a day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: C	Drug: HEC-based Placebo Gel; intravaginal gel, dosed daily
Experimental: A	Drug: Dapivirine Gel 4750, 0.05%, 2.5g; intravaginal gel, dosed daily
Experimental: B	Drug: Dapivirine Gel 4789, 0.05%, 2.5g; intravaginal gel, dosed daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serial dapivirine concentrations in plasma, vaginal fluid and cervical-vaginal tissue samples	11 days
Self-reported genital symptoms, pelvic/colposcopic exam findings, laboratory evaluations and adverse events/serious adverse events	14 days

Collaborators and Investigators

• Sponsor: International Partnership for Microbicides, Inc.
• Investigators: Study Director: Dr. Annalene Nel, IPM

Publications and helpful links

General Publications

• Nel A, Smythe S, Habibi S, Romano J. 2009. Comparison of Safety and PK of Two Formulations of Dapivirine Vaginal Gel in Healthy, HIV-Negative Women [abstract]. 16th Conference on Retroviruses and Opportunistic Infections; 2009 Feb 8-11; Montreal. Available from: http://www.retroconference.org/2009/PDFs/1065.pdf

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: January 31, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): March 27, 2009
• Last Update Submitted That Met QC Criteria: March 26, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: HIV Seronegativity; HIV-1 Infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Dapivirine
• Other Study ID Numbers: IPM 012