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J Int AIDS Soc. 2018 Aug;21(8):e25156. doi: 10.1002/jia2.25156.

FAME-04: A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovir.

Author information

1
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
2
Magee-Womens Research Institute, Pittsburgh, PA, USA.
3
Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
Department of Health and Human Services, Kelly Government Solutions, Contractor to National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
5
CONRAD, Eastern Virginia Medical School, Arlington, VA, USA.
6
Alpha StatConsult, Damascus MD, USA.
7
Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

INTRODUCTION:

Fast-dissolving vaginal film formulations release antiretroviral drugs directly into vaginal fluid and may be as efficient at drug delivery yet more acceptable to women than gels. In this Phase 1 vaginal film study, the safety, acceptability, pharmacokinetics and pharmacodynamics of two doses of tenofovir (TFV) film and TFV 1% gel were compared to corresponding placebo formulations.

METHODS:

Seventy-eight healthy HIV negative women were randomized to self-insert daily vaginal film (10 mg TFV, 40 mg TFV or placebo) or 4 mL of vaginal gel (TFV 1% [40 mg] or placebo) for seven days. Grade 2 and higher adverse events (AEs) related to study product were compared across study arms using Fisher's exact test. Plasma TFV concentrations were measured before and 2 hours after last product use. Paired cervical and vaginal tissue biopsies obtained 2 hours after the last dose were measured to determine tenofovir diphosphate (TFV-DP) concentrations and exposed to HIV in an ex vivo challenge assay. Acceptability was assessed through questionnaire.

RESULTS:

There was only one grade 2 or higher related AE, the primary endpoint; it occurred in the placebo gel arm. AEs occurred in 90% of participants; the majority (91%) were grade 1. AEs were similar across study arms. TFV concentrations in plasma and TFV-DP concentrations in cervical and vaginal tissues were comparable between 40 mg TFV film and the TFV gel groups. There was a significant relationship between reduced viral replication and TFV-DP concentrations in cervical tissues. Film users were less likely to report product leakage than gel users (66% vs. 100%, p < 0.001).

CONCLUSIONS:

Films were safe and well tolerated. Furthermore, films delivered TFV to mucosal tissues at concentrations similar to gel and were sufficient to block HIV infection of genital tissue ex vivo.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01989663.

KEYWORDS:

microbicide; prevention; tenofovir; vaginal film; vaginal gel

PMID:
30101439
PMCID:
PMC6088248
DOI:
10.1002/jia2.25156
[Indexed for MEDLINE]
Free PMC Article

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