A Phase I Study to Evaluate the Pharmacokinetic Drug‒Drug Interaction of HP501, Febuxostat, and Colchicine in Male Chinese Patients with Hyperuricemia

Ding, Ruilin; Chen, Longxia; Li, Xinghai; Xiong, Tengqiong; Chen, Hong; Hu, Xiaojing; Li, Yun; Zhou, Yi; Liu, Kezhi; Wu, Jianhong; Jiang, Feng; Peng, Qicong

doi:10.1007/s40261-023-01274-7

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(2 citation statements)

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“…Compared to these historical data, hyperuricemic patients receiving 50–120 mg of HP501 for 10 days had a much higher plasma exposure to HP501 in this study. The mean t 1/2 of HP501 at steady state was 11.77–13.47 h, which is consistent with previous studies 12 , 16 . Following daily dosing of HP501 for 10 days, the mean R ac was 1.282–1.413 in the 5 cohorts, indicating no obvious accumulation of HP501 during the study period.…”

Section: Discussionsupporting

confidence: 92%

“…During the phase I/IIa trial of HP501, hyperuricemic patients received 45 mg of HP501 for 10 days, and 2/10 and 3/10 patients had elevated AST and ALT levels, respectively 12 . Another phase I trial evaluating the drug-drug interaction of HP501, febuxostat, and colchicine, showed that 1 out of 14 patients who received 40 mg HP501 once daily for 7 days had elevated ALT levels 16 . Due to the previous studies of HP501, we specially focused on the hepatotoxicity of HP501 in this study.…”

Section: Discussionmentioning

confidence: 99%

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A dose-escalation study of HP501, a highly selective URAT1 inhibitor, in male Chinese patients with hyperuricemia

Ding,

Deng,

Chen

et al. 2023

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HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor used for treating hyperuricemia. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of HP501 in male Chinese patients. Patients with hyperuricemia were sequentially assigned to receive oral doses of HP501 (30, 50, 60, 90, and 120 mg) as a single dose on Day 1 and as once-daily doses from Days 4 to 13. Safety, pharmacokinetic, and pharmacodynamic data were collected. Multiple oral doses of HP501 were well-tolerated in all the cohorts. The most common adverse events (≥ 10% of patients) of any grade regardless of drug relationship were gout flare (14 patients, 25.93%), diarrhea (12 patients, 22.22%), elevated ALT (8 patients, 14.81%), hypertriglyceridemia (7 patients, 12.96%), dry mouth (7 patients, 12.96%) and oral ulcer (7 patients, 12.96%). All adverse events were mild or moderate. The Cmax and exposure (AUC) of HP501 was approximately dose-proportional between 30 and 120 mg. A dose-dependent serum uric acid (UA)-lowering effect was observed in the dose range of 30 to 60 mg and the serum UA lowering effect was similar between 90 and 120 mg on day 13, indicating that the maximal serum UA lowering effect of HP501 was achieved at 90 mg in the patients with hyperuricemia. In conclusion, the tolerability, pharmacokinetics, and pharmacodynamics supported 90 mg HP501 for subsequent clinical studies of this highly selective URAT1 inhibitor.Clinical Trial registration: No. CTR20212259 (http://www.chinadrugtrials.org.cn/) was registered in September 2021, and No. CTR20222257 was registered in September 2022.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%