A phase I study to evaluate the safety, tolerability, and pharmacokinetics of a novel, potent GABA analog HSK16149 in healthy Chinese subjects

Qian Chen; Qian Chen; Qian Chen; Qingqing Wu; Qingqing Wu; Qingqing Wu; Rong Song; Rong Song; Rong Song; Yating Wang; Yating Wang; Yating Wang; Mengqi Zhang; Mengqi Zhang; Mengqi Zhang; Fangqiong Li; Weifang Zeng; Wei Wang; Wei Wang; Wei Wang; Jingying Jia; Jingying Jia; Jingying Jia; Chen Yu; Chen Yu; Chen Yu; Yanmei Liu; Yanmei Liu; Yanmei Liu

doi:10.3389/fphar.2023.1296672

Frontiers in Pharmacology (Dec 2023)

A phase I study to evaluate the safety, tolerability, and pharmacokinetics of a novel, potent GABA analog HSK16149 in healthy Chinese subjects

Qian Chen,
Qian Chen,
Qian Chen,
Qingqing Wu,
Qingqing Wu,
Qingqing Wu,
Rong Song,
Rong Song,
Rong Song,
Yating Wang,
Yating Wang,
Yating Wang,
Mengqi Zhang,
Mengqi Zhang,
Mengqi Zhang,
Fangqiong Li,
Weifang Zeng,
Wei Wang,
Wei Wang,
Wei Wang,
Jingying Jia,
Jingying Jia,
Jingying Jia,
Chen Yu,
Chen Yu,
Chen Yu,
Yanmei Liu,
Yanmei Liu,
Yanmei Liu

Affiliations

Qian Chen: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Qian Chen: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Qian Chen: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Qingqing Wu: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Qingqing Wu: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Qingqing Wu: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Rong Song: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Rong Song: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Rong Song: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Yating Wang: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Yating Wang: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Yating Wang: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Mengqi Zhang: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Mengqi Zhang: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Mengqi Zhang: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Fangqiong Li: Haisco Pharmaceutical Group Co., Ltd., Chengdu, China
Weifang Zeng: Haisco Pharmaceutical Group Co., Ltd., Chengdu, China
Wei Wang: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Wei Wang: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Wei Wang: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Jingying Jia: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Jingying Jia: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Jingying Jia: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Chen Yu: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Chen Yu: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Chen Yu: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China
Yanmei Liu: Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China
Yanmei Liu: Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China
Yanmei Liu: Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China

DOI: https://doi.org/10.3389/fphar.2023.1296672
Journal volume & issue: Vol. 14

Abstract

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Purpose: HSK16149 is a novel, potent gamma-aminobutyric acid (GABA) analog for the treatment of neuropathic pain. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of HSK16149 after single and multiple doses in healthy Chinese subjects.Methods: The randomized, double-blind, placebo-controlled study comprised two parts: SAD (single ascending-dose study) and MAD (multiple ascending-dose study). A total of 122 healthy subjects were enrolled in this study. HSK16149 capsule or placebo was administered as the protocol required. The safety of the drug was evaluated through clinical examinations and adverse events. Blood and urine samples were collected at the designated time intervals for pharmacokinetic analysis.Results: Subjects were generally well tolerated after HSK16149 administration and the most common treatment-emergent adverse event (TEAEs) was dizziness, which was expected based on the mechanism of action of HSK16149. In SAD, AUC and Cmax were shown to have a dose-proportional relationship in the dose range of 5-120 mg. The t1/2 of HSK16149 is 3.7-6.4 h. In MAD, after a single and multiple administration of 15-80 mg, AUC and Cmax are proportional to the increased dose of HSK16149, and the accumulative ratios of AUC and Cmax at steady-state were 1.05–1.44 and 1.07–1.36, respectively, indicating that HSK16149 only accumulated slightly after repeated administration.Conclusion: HSK16149 was well tolerated in healthy Chinese subjects. Based on the safety and pharmacokinetic data, 80 mg twice daily (BID) was suggested as the highest target dose for further clinical development.Clinical Trial Registration:http://www.chinadrugtrials.org.cn, identifier CTR20182535 and CTR20191317

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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