Clinical Studies of Films

Magee-Women'S Res Inst And Foundation, Pittsburgh PA

Investigators

Linked publications & trials

Abstract

PROJECT 3 ABSTRACT The overarching goal of the FAME program is to develop a film formulation of the integrase inhibitor MK-2048 that achieves cervical and vaginal tissue drug levels for one week following a single application. The broad goal of this clinical project is to establish the feasibility of this approach by demonstrating that a single film inserted intravaginally will provide adequate drug levels to the vaginal and cervical tissues to reduce infection when challenged with HIV ex vivo up to 7 days after film application. The rationale for the development of an on demand, coital-independent vaginal microbicide film is based on the increased recognition that daily use products containing ARVs have had insufficient adherence in the young populations of women at the highest risk of HIV to be effective. Our team has demonstrated that vaginal films can deliver the antiretroviral drug dapivirine at levels similar to those achieved by rings or gel formulations. Project 1 and the IND Enabling Project 4 of the FAME program will develop a vaginal film which can be tested in pharmacokinetic and pre- Phase 1 studies of safety and efficacy. Therefore, we propose to: 1) conduct a sequence randomized crossover study of two placebo films containing different polymers in order to test the hypothesis that film excipients differentially impact the vaginal mucin proteins, glycome and microbiome; 2) perform a dose selection pharmacokinetic study of a 15 and 30 mg MK-2048 film and then use this dose to 3) conduct a pre- Phase 1 randomized, placebo-controlled study of an MK-2048 film which will assess the safety, pharmacokinetics, and pharmacodynamics of the MK-2048 film at 1, 3, 5 and 7 days after a single application using the ex vivo challenge model. Throughout the film evaluation process, we will incorporate a behavioral decision science approach to produce an in-depth understanding of how women perceive and understand vaginal microbicide films. To do this, we will assess user perceptions, acceptability, understanding and correct use of microbicide films through mental models research, and to use those findings to create an intervention tool aimed at addressing misconceptions and promoting acceptability and adherence.