Safety, pharmacokinetics and pharmacodynamics of a novel γ-aminobutyric acid (GABA) receptor potentiator, HSK3486, in Chinese patients with hepatic impairment

Abstract

Background

The primary objective of this study was to investigate if hepatic impairment alters the safety, pharmacokinetics, and pharmacodynamics of HSK3486.

Research design and methods

This was a clinical trial of HSK3486 in subjects with normal hepatic function (n = 8), and mild (Child-Pugh A; n = 8), or moderate (Child-Pugh B; n = 8) hepatic impairment. Each subject received an IV bolus dose of 0.4 mg/kg HSK3486 for 1 min, immediately followed by a maintenance infusion of 0.4 mg/kg/h HSK3486 for 30 min.

Results

In total, 24 subjects were enrolled and completed the study. HSK3486 was generally well tolerated by all subjects. There were no serious AEs and no deaths reported during the study. The incidence of AEs was numerically highest in subjects with moderate hepatic impairment. The exposure (AUC) of HSK3486 increased gradually with the decrease in hepatic function; however, degree of hepatic impairment had little effect on HSK3486 PD (MOAA/S and BIS).

Conclusions

Overall, there were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to normal control. These data imply that HSK3486 dose adjustment is not warranted in subjects with mild or moderate hepatic impairment.

Trial registration

The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04145596).

Key Message

• HSK3486 at an IV bolus dose of 0.4 mg/kg and a maintenance infusion of 0.4 mg/kg/h was safe and well tolerated by all mild or moderate hepatic impairment subjects and normal hepatic function subjects.

• There were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to subjects with normal hepatic function.

• HSK3486 dose adjustment is not required in subjects with mild or moderate hepatic impairment.

Keywords:

• Efficacy
• hepatic impairment
• HSK3486
• pharmacokinetics
• safety

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

No potential conflict of interest was reported by the author(s). Pangke Yan, Nan Wu, Xiao Liu, Shiping Ma, Xu Wang are the employees of Haisco Pharmaceutical Group.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author Xiaojiao Li.

Additional information

Funding

This work was financially supported by the capital construction funds within the provincial budget in 2020 (innovation capacity construction, project: 2020C038-1), the National Natural Science Foundation of China (Project: 82104314) and Norman Bethune Program of Jilin University [2022B18].