The safety and pharmacokinetics of a novel, selective S1P1R modulator in healthy participants. (2nd April 2020)

• Record Type: Journal Article
• Authors: Singhal, Shalabh; Girgis, Ihab G.; Xie, Jenny; Dutta, Santanu; Shevell, Diane E.; Throup, John
• Is Part Of: Expert opinion on investigational drugs. Volume 29:Number 4(2020)
• Page Start: 411
• Page End: 422
• Publication Date: 2020-04-02
• Subjects: Absolute lymphocyte count -- BMS-986166; pharmacodynamics -- pharmacokinetics -- S1P1R -- safety; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2020.1742322
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Background : Safety, pharmacokinetics and pharmacodynamics of BMS-986166, a novel sphingosine-1-phosphate receptor 1 modulator, were assessed. Research design and methods : Two double-blind, placebo-controlled, randomized Phase l studies were conducted in healthy participants. In the single ascending dose study (N = 70), BMS-986166 was administered as a single dose, upwardly titrated daily doses or a single dose in participants who were fed, fasted or administered famotidine. In the multiple ascending dose study (N = 32), BMS-986166 was administered daily for 28 days. Safety, pharmacokinetics and pharmacodynamics (absolute lymphocyte count [ALC]) were assessed. Results : BMS-986166 was generally well tolerated; treatment-related adverse events were mild. Dose-related, clinically insignificant reductions in time-matched heart rate were recorded versus placebo. Pharmacokinetics were linear and stationary with approximately dose-related increases in blood exposure of BMS-986166. Decreases in ALC percent change from baseline with multiple doses of BMS-986166 versus placebo were dose-related. Between Day 0 and 35, median nadir lymphocyte reductions were 53.7%, 75.9% and 81.9% with 0.25-, 0.75- and 1.5-mg BMS-986166 doses. ALC recovery began 14, 14–21 and 7 days after last dose of 0.25, 0.75 and 1.5 mg. Conclusions : BMS-986166 was generally well tolerated in this population and warrants further investigation. Trial registration : ClinicalTrials.gov: NCT02790125, NCT03038711.