Journal
CLINICAL THERAPEUTICS
Volume 37, Issue 2, Pages 338-348Publisher
ELSEVIER
DOI: 10.1016/j.clinthera.2014.10.001
Keywords
multiple ascending dose trial; opioid receptor antagonist; pharmacokinetics; safety; samidorphan; single ascending dose trial; tolerability
Categories
Funding
- Alkermes Inc.
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Purpose: Samidorphan (3-carboxamido-4-hydroxy naltrexone) is a novel opioid receptor antagonist that is currently in clinical development. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in 2 double-blind, placebo-controlled, randomized studies in healthy adults. Methods: The first study investigated single, ascending doses of 3.7 to 55.7 mg of samidorphan in 16 healthy adults; the second study evaluated multiple ascending doses of 10 or 20 mg of samidorphan administered for 7 days in 30 healthy adults. Findings: Across the two studies, 39 of 46 subjects were male; 32 were white, 11 were black, and 3 were hispanic. Mean age was 34.9 years and mean weight was 84.2 kg. In both studies, samidorphan was rapidly absorbed, with a Tmax of 1 hour, and AUC increased with increasing dose. Samidorphan plasma levels declined in a monoexponential manner, with a half-life of similar to 7 to 9 hours. After multiple doses, steady state was approached by day 6 and achieved by day 7 after the 10-mg dose, but steady state was not reached for the 20-mg dose. Accumulation was low, with accumulation ratios <1.65. In both studies, samidorphan was generally well tolerated, with somnolence reported as the most common adverse event. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.
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