Safety, Tolerability and Pharmacokinetics of Single-dose Oral SYHA1402 in Chinese Healthy Subjects

Abstract

Abstract Objective To assess the safety, tolerability and pharmacokinetics of a single dose of SYHA1402 in Chinese healthy subjects. Methods This was a randomized, double-blind, placebo-controlled, single-ascending dose study in healthy subjects. Subjects received a single dose of 25mg (n = 4), 50mg (n = 8), 100mg (n = 8), 200mg (n = 8), 400mg (n = 8), 800mg (n = 6) or matching placebo (n = 12, 2 in each dose group). We assessed safety and tolerability throughout the study. The pharmacokinetic (PK) parameters of SYHA1402 were estimated using non-compartmental analysis. Results In all, 54 subjects were enrolled and completed the study. Specifically, there were no deaths, serious adverse events, or withdrawals from study due to adverse events. All treatment-emergent adverse events were mild. The most common drug-related adverse event was sinus bradycardia. The time to maximum concentration ranged from 1.13 to 2.25 h. The terminal elimination half-life range of SYHA1402 was 1.51 h to 4.70 h. SYHA1402 exhibited nonlinear PKs with less than dose-proportional increases in exposure after single oral doses of 25 mg to 800 mg. Fe0 − 72h from urine of SYHA1402 in each dose group from 25 mg to 800 mg was 64.08%, 57.97%, 59.28%, 24.64%, 8.49%, 7.15%, respectively. Conclusion Single dose of SYHA1402 was well tolerated and safe over the dose range of 25–800 mg. More than 50% of the unchanged SYHA1402 were excreted in urine within the dose range of 25–100 mg. With the dose increasing to 800 mg, the urine excretion amount of SYHA1402 gradually tends to saturation. Trial registration number NCT03988413 (https://www.clinicaltrials.gov/) Trial registration date June 17, 2019 Date of first patient’s enrollment: August 5, 2019