3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

OVERVIEW OF PHASE 1 AND 2A SAFETY AND EFFICACY DATA OF MARAVIROC (UK-427,857)

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuOa0204

McHale M., Abel S., Russell D., Gallagher J., van der Ryst E.
Pfizer Global Research and Development, Sandwich, United Kingdom

INTRODUCTION: To summarise safety and efficacy data from selected multiple dose Phase 1/2a studies of maraviroc (UK-427,857), a CCR5 antagonist, in healthy volunteers and HIV-positive patients.

METHODS: Six multiple dose studies where maraviroc was adminstered alone were reviewed. These studies included 7 days of dosing at the maximum dose studied of 1200mg QD and 28 days of dosing at the highest proposed clinical dose of 300mg BID.

RESULTS: A total of 195 subjects (66 HIV+) were dosed with maraviroc, including 40 women. The most common treatment related adverse events were headache, dizziness, nausea, asthenia, flatulence and rhinitis. The majority of the adverse events were graded as mild or moderate. At doses up to and including 300mg BID the adverse event profile was similar to that of placebo. No serious adverse events were reported, with few (5) treatment related discontinuations (3 with postural hypotension [2 on 600mg QD and 1 on placebo], 1 with elevated transaminases [3mg BID] and 1 with rash [placebo]). Clinically significant increases in liver function tests occurred in 7 subjects at varying doses of maraviroc with no clear frequency/dose relationship (4 subjects had >3×ULN transaminases and 3 subjects had >1.25 to <2×ULN bilirubin). Mild/moderate elevations in creatinine (<2×ULN) were noted in one study at 1200mg QD and placebo. There was no dose related change in QTcF. Ten-day monotherapy with maraviroc at doses of 300mg QD and 300mg BID in HIV+ patients resulted in mean maximum HIV RNA reductions of 1.60 and 1.84 log₁₀, respectively.

CONCLUSIONS: The development program to date has demonstrated that maraviroc is well tolerated at doses up to and including 300mg BID and that 10 day monotherapy resulted in significant reductions in viral load. These results indicate that further evaluation of maraviroc for the treatment of HIV infection is merited.

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050724
Basic | TuOa0204 | E. van der Ryst
New antiretroviral agents

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