Dataset Information

Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.

ABSTRACT: BMS-986142 is an oral, small-molecule reversible inhibitor of Bruton's tyrosine kinase. The main objectives of our phase I studies were to characterize the safety and tolerability, pharmacokinetics, and pharmacodynamics of BMS-986142 in healthy participants, and to investigate the potential for the effect of BMS-986142 on the PK of methotrexate (MTX) in combination.In a combined single ascending dose and multiple ascending dose study, the safety, pharmacokinetics, and pharmacodynamics of BMS-986142 were assessed in healthy non-Japanese participants following administration of a single dose (5-900 mg) or multiple doses (25-350 mg, once daily for 14 days). In a drug-drug interaction study, the effect of BMS-986142 (350 mg, once daily for 5 days) on the single-dose pharmacokinetics of MTX (7.5 mg) was assessed in healthy participants.BMS-986142 was generally well tolerated, alone and in combination with MTX. BMS-986142 was rapidly absorbed with peak concentrations occurring within 2 h, and was eliminated with a mean half-life ranging from 7 to 11 h. Exposure of BMS-986142 appeared dose proportional within the dose ranges tested. A dose- and concentration-dependent inhibition of CD69 expression was observed following administration of BMS-986142. BMS-986142 did not affect the pharmacokinetics of MTX.BMS-986142 was well tolerated at the doses tested, had pharmacokinetic and pharmacodynamic profiles which support once-daily dosing, and can be coadministered with MTX without the pharmacokinetic interaction of BMS-986142 on MTX.

SUBMITTER: Lee SK

PROVIDER: S-EPMC5423977 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.

Lee Sun Ku SK Xing Jun J Catlett Ian M IM Adamczyk Robert R Griffies Amber A Liu Ang A Murthy Bindu B Nowak Miroslawa M

European journal of clinical pharmacology 20170306 6

<h4>Purpose</h4>BMS-986142 is an oral, small-molecule reversible inhibitor of Bruton's tyrosine kinase. The main objectives of our phase I studies were to characterize the safety and tolerability, pharmacokinetics, and pharmacodynamics of BMS-986142 in healthy participants, and to investigate the potential for the effect of BMS-986142 on the PK of methotrexate (MTX) in combination.<h4>Methods</h4>In a combined single ascending dose and multiple ascending dose study, the safety, pharmacokinetics, ...[more]

PMID: 28265691

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Dataset Information

Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.

Publications

Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.

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