A Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of HP501 in Male Chinese Gout Patients with Hyperuricemia.

HP501, a novel highly selective renal urate transporter 1 (URAT1) inhibitor, represents a promising therapeutic option for hyperuricemia. This Phase I study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HP501 in Chinese gout patients. 37 patients with gout and hyperuricemia were enrolled in this single-center, open-label, dose-escalation study. Participants were sequentially assigned to receive HP501 at 60, 80, and 100 mg twice daily (BID) following single- and multiple-dose regimens. Safety assessments, PK parameters, and PD reductions were systematically evaluated. HP501 demonstrated an acceptable safety and tolerability profile across all dose cohorts. The most common adverse events (≥10% of patients) included gout flare (36.1%), prostatic hypertrophy (36.1%), elevated ALT (16.7%), and kidney stones (11.1%), all of which were mild to moderate in severity. PK analysis revealed dose-proportional increases in Cmax and AUC (60 to 100 mg BID), with corresponding dose-dependent reductions in serum UA levels. All patients achieved therapeutic UA targets (<360 µmol/L). These findings support the clinical advancement of HP501, with 60 to 100 mg BID identified as the recommended dose range for further investigation in subsequent trials. However, these findings are preliminary and limited by the single-center design, small sample size, and exclusion of female patients, warranting confirmation in larger, more diverse populations.