A Randomized, Open-Label, Crossover Phase 1 Safety and Pharmacokinetic Study of Oral Maraviroc and Maraviroc 1% Gel (the CHARM-03 Study)
Year: 2021
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: The Combination HIV Antiretroviral Rectal Microbicide-3 (CHARM-03) study was a randomized, open-label, crossover Phase 1 safety and pharmacokinetic (PK) study of oral maraviroc (MVC) and MVC 1% gel. At a single site, healthy HIV-uninfected men and women were enrolled and randomized to an open label crossover sequence of eight consecutive daily exposures to MVC 300 mg dosed orally, MCV 1% gel dosed rectally, and MVC 1% gel dosed vaginally. Male participants received oral and rectal dosing and female participants received oral, rectal, and vaginal dosing. Assessments were undertaken at baseline and following each 8-day period and included collection of plasma, rectal/cervical tissue (CT), and rectal/endocervical/vaginal fluids. Eleven men and nine women were enrolled. Two participants withdrew from the study before receiving study product. There were 25 adverse events, of which 24 were Grade 1 (G1) and one was G2 (unrelated). After eight doses, MVC was quantifiable in all samples following oral, rectal, or vaginal product administration. The highest drug concentrations in plasma, rectal tissue (RT), and CT were associated with oral, rectal, and vaginal drug delivery, respectively. There were significant reductions in tissue drug concentrations when rectal and cervical biopsies were incubated in media before tissue processing for PK ( p < .0001). Only oral MVC was associated with limited protection in the rectal explant HIV challenge model ( p < .05). There were no immunological changes in RT, and all products were acceptable to participants. In conclusion, all products were found to be safe and acceptable and did not induce local inflammation. The lack of ex vivo efficacy demonstrated in study samples may be due to rapid disassociation of MVC from the explant tissue. ClinicalTrials.gov Identifier: NCT02346084.
Authors: Ian M. McGowan, Sylvain Chawki, Craig W. Hendrix, Peter A. Anton, Mark A. Marzinke, Rhonda M. Brand, Jarret C. Engstrom, Lisa C. Rohan, Kaleab Z. Abebe, Nicola Richardson-Harman, Aaron Siegel, Alex Reinhart, John Steytler, Ronald Stall, Hans Spiegel, Beatrice Chen, Sharon L. Achilles, Cindy E. Jacobson, Elena Khanukova, Ross D. Cranston
Institutions: University of Pittsburgh, Magee-Womens Research Institute, Inserm, Assistance Publique – Hôpitaux de Paris, Department of Virology, Hôpital Saint-Louis, Johns Hopkins University, University of California, Los Angeles, ViiV Healthcare (United Kingdom), International Partnership for Microbicides, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Universitat de Barcelona
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3193258759