Safety, tolerability, pharmacokinetics, and pharmacodynamics of ABP-671 in healthy participants and patients with hyperuricemia and gout: a proof-of-concept study

Background This proof-of-concept study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABP-671, a novel URAT1 inhibitor, in healthy participants and in patients with hyperuricemia and gout.Methods This single-center, randomized, double-blind, placebo-controlled phase I/IIa clinical trial consisted of two parts: a single ascending dose study (SAD) in healthy participants (0.5, 1, 3, and 6 mg, with two participants receiving placebo and six participants receiving ABP-671 tablets per dose cohort), and a multiple ascending dose (MAD) study in patients with hyperuricemia and gout (1, 2, 4, 6 and 12 mg daily, with two patients receiving placebo and seven patients receiving ABP-671 tablets per cohort).Results Thirty-two and 45 Chinese participants were enrolled in the SAD and MAD studies, respectively. In the SAD and MAD studies, eight (25.0%) and 24 (53.3%) participants reported treatment-emergent adverse events (TEAEs), respectively; there were no serious AEs (SAEs), and no grade ≥ 3 TEAEs. In the MAD study, the maximum mean serum urate decrease from baseline in patients with gout was 17.7% (placebo), 56.4% (1 mg QD), 58.1% (2 mg QD), 69.4% (4 mg QD), 77.0% (6 mg QD), and 79.2% (12 mg QD), respectively. The maximum mean serum urate decrease from baseline in serum urate in patients with hyperuricemia was 19.9% (placebo), 50.1% (1 mg QD), 64.1% (2 mg QD), 73.2% (4 mg QD), 81.2% (6 mg QD), and 82.1% (12 mg QD), respectively.Conclusions ABP-671 had an acceptable safety profile in Chinese healthy participants and patients with hyperuricemia and gout. ABP-671 reduced serum urate levels in a dose-dependent manner.Trial registration https://chinadrugtrials.org.cn (No. CTR20211668) .