In:
British Journal of Clinical Pharmacology, Wiley, Vol. 84, No. 5 ( 2018-05), p. 876-887
Abstract:
The aims of the present study were to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS‐962212, a first‐in‐class factor XIa inhibitor, in Japanese and non‐Japanese healthy subjects. Methods This was a randomized, placebo‐controlled, double‐blind, sequential, ascending‐dose study of 2‐h (part A) and 5‐day (part B) intravenous (IV) infusions of BMS‐962212. Part A used four doses (1.5, 4, 10 and 25 mg h −1 ) of BMS‐962212 or placebo in a 6:2 ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h −1 ) enrolling Japanese ( n = 4 active, n = 1 placebo) and non‐Japanese ( n = 4 active, n = 1 placebo) subjects per dose. The PK, PD, safety and tolerability were assessed throughout the study. Results BMS‐962212 was well tolerated; there were no signs of bleeding, and adverse events were mild. In parts A and B, BMS‐962212 demonstrated dose proportionality. The mean half‐life in parts A and B ranged from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure‐dependent changes were observed in the PD parameters, activated partial thromboplastin time (aPTT) and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change from baseline at 20 mg h −1 in part B was 92% and 90%, respectively. No difference was observed in weight‐corrected steady‐state concentrations, aPTT or FXI:C between Japanese and non‐Japanese subjects ( P 〉 0.05). Conclusion BMS‐962212 has tolerability, PK and PD properties suitable for investigational use as an acute antithrombotic agent in Japanese or non‐Japanese subjects.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
1498142-7
SSG:
15,3
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