Title: Pharmacokinetics and safety of apremilast (CC-10004) in subjects with hepatic impairment

Authors: Mahmoud S. Assaf; Eric Laille; Liangang Liu; Edward O'Mara; Anfan Wu; Maria Palmisano; Thomas C. Marbury; Richard A. Preston

Addresses: Translational Development – Clinical Pharmacology, Celgene Corporation, Summit, New Jersey, USA ' Translational Development – Clinical Pharmacology, Celgene Corporation, Summit, New Jersey, USA ' Translational Development – Clinical Pharmacology, Celgene Corporation, Summit, New Jersey, USA ' Translational Development – Clinical Pharmacology, Celgene Corporation, Summit, New Jersey, USA ' Translational Development – Clinical Pharmacology, Celgene Corporation, Summit, New Jersey, USA ' Translational Development – Clinical Pharmacology, Celgene Corporation, Summit, New Jersey, USA ' Orlando Clinical Research Center, Orlando, Florida, USA ' Division of Clinical Pharmacology, University of Miami, Miami, Florida, USA

Abstract: Apremilast (CC-10004), a PDE4 enzyme inhibitor, is under clinical development for the treatment of inflammatory immune-mediated disorders. Since apremilast is extensively metabolised via multiple routes, impact of hepatic impairment on the pharmacokinetics (PK) of apremilast and M12 metabolite was evaluated. Thirty-two subjects were enrolled in a two-centre, open-label, and single-dose study. Subjects with moderate hepatic impairment and their healthy matches received a single 30-mg dose and subjects with severe hepatic impairment and their healthy matches received a single 20-mg dose of apremilast. Plasma concentrations of apremilast and M12 were measured, PK parameters calculated, and statistically compared. During the study, single doses of apremilast were well tolerated, with no clinically meaningful safety findings observed. PK parameters were comparable between hepatic impaired and healthy subjects, and there was no evidence to suggest that the PK of apremilast is affected by moderate and severe hepatic impairment. Therefore, no dose adjustment is required.

Keywords: hepatic impairment; hepatic metabolism; pharmacokinetics; phosphodiesterase 4; PDE4 enzyme inhibitor; apremilast; immune-mediated disorders; inflammatory disorders; M12 metabolite; safety; dose adjustment.

DOI: 10.1504/IJMEI.2014.060246

International Journal of Medical Engineering and Informatics, 2014 Vol.6 No.2, pp.100 - 114

Available online: 01 Apr 2014 *

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