Pharmacokinetics and Safety Evaluation of the Transglutaminase 2 Inhibitor Suvigletistat in Healthy Chinese, Japanese, and White/European Participants.

This Phase I, randomized, placebo-controlled, double-blind study (NCT06625489) evaluated pharmacokinetics (PK), safety, and tolerability of the transglutaminase 2 inhibitor suvigletistat in Chinese, Japanese, and White/European participants. Eligible participants: aged 18-50 years, healthy, and of Chinese, Japanese, or White/European ancestry. Thirty-six participants (12 per ancestry group) were randomized 3:1 to receive suvigletistat (160 mg single oral dose) or placebo. Suvigletistat was rapidly absorbed (median time to maximum observed drug concentration [Cmax]: 0.67-0.75 h), and geometric mean half-life ranged from 1.93 to 2.58 h across ancestry groups. Suvigletistat systemic exposure was similar across all ancestries; geometric least squares mean ratios versus White/European participants for Cmax were 0.99 and 1.06 in participants of Chinese and Japanese ancestry, respectively. Similarly, area under the concentration-time curve from time zero to infinity ratios were 0.94 and 1.06. Suvigletistat geometric mean elimination half-life was comparable in Chinese (1.93 h), Japanese (2.23 h), and White/European participants (2.58 h). There were no serious adverse events or deaths. There were no clinically meaningful findings in laboratory values, vital signs, or electrocardiograms. No clinically meaningful differences in suvigletistat PK were observed between ancestry groups, providing evidence of low ethnic sensitivity for a drug with cytochrome P450 3A4-dependent metabolism.