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

Abstract

Abstract Introduction To assess the safety, tolerability and pharmacokinetics of a single dose of SYHA1402 in healthy Chinese subjects. Methods This was a randomized, double-blind, placebo-controlled, single-ascending dose study in healthy subjects. Subjects received a single dose of SYHA1402 25 mg, 50 mg, 100 mg, 200 mg, 400 mg or 800 mg, or matching placebo. Safety and tolerability were assessed 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, and the terminal elimination half-life range was 1.51–4.70 h. SYHA1402 exhibited nonlinear PK parameters with less than dose-proportional increases in exposure after single oral doses of 25 to 800 mg. Conclusion SYHA1402 administered as a single dose was well tolerated and safe over the dose range of 25–800 mg. More than 50% of the unchanged SYHA1402 was excreted in urine within the dose range of 25–100 mg. Trial registration NCT03988413 ( https://www.clinicaltrials.gov/ ; registration date: 17 June 2019).

Keywords

• Aldose reductase inhibitor
• Diabetic peripheral neuropathy
• Pharmacokinetics
• Safety