Background The primary objective of this study was to investigate if hepatic impairment alters the safety, pharma c okinetics, 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.

This study shows that yimitasvir phosphate was well tolerated, and the PK profile supported daily dosing regimens. A 1-week (7-day) treatment course led to a quick and significant reduction in HCV RNA level in this cohort with HCV GT-1 infection.

Sarpogrelate is widely used to treat peripheral vascular disorders. However, it has been demonstrated to have a poor pharmacokinetic (PK) profile and marked within‐subject variability. Here, the bioequivalence of 2 formulations of sarpogrelate (100‐mg tablets) was assessed by using the reference‐scaled average bioequivalence (RSABE) method, and the PK parameters were quantified in healthy Chinese subjects under fasting (n = 38) and fed (n = 35) conditions. In this open and randomized 4‐way replicate study, a single dose of sarpogrelate was administered followed by a 3‐day washout period. The sarpogrelate concentration in blood samples was measured by liquid chromatography‐tandem mass spectrometry within 6 hours (fasting) or 10 hours (fed) of drug administration, and the PK parameters were determined by a noncompartmental model. The bioequivalence of the 2 formulations under both conditions was assessed using the ratios of ln(peak concentration [Cmax]) and ln(area under the concentration‐time curve [AUC]) within the limits based on the RSABE method. The 90% CIs for the ratios of lnCmax, lnAUC0‐t, and lnAUC0‐∞ were 0.8531–1.1100, 0.9616–1.0737, and 0.9550–1.0684, respectively, under fasting conditions and 0.8918–1.1076, 0.9818–1.0694, and 0.9818–1.0686, respectively, under fed conditions, which were within the RSABE acceptance limits. Food intake decreased the systemic exposure and the Cmax of sarpogrelate by 0.9‐fold and 0.5‐fold, respectively.

GST-HG131, a novel dihydroquinolizinone (DHQ) compound, has been shown to reduce circulating levels of HBsAg in animals. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetic profile of GST-HG131 in healthy Chinese subjects.

A recombinant human serum albumin-interferon alpha2a fusion protein (rHSA/IFNα2a) is expected to extend the half-life of IFNα2a. This study aims to evaluate the tolerability, safety and efficacy of rHSA/IFNα2a. METHODSThis is an open, randomized, positive control, multiple-dose ascending Phase Ib study. A panel of 32 treatment naïve and noncirrhotic chronic hepatitis B patients were divided into four cohorts, and each received 600, 750 or 900 μg of rHSA/IFNα2a or 180 μg of PEG-IFNα2a for 3 months. Tolerability, pharmacokinetics and antiviral responses were assessed. RESULTSThirty-one of 32 enrolled patients completed the treatment study. The rHSA/IFNα2a treatment was better tolerated than the PEGIFNα2a 180 μg treatment, as evidenced by blood cell counts and higher serum albumin levels. Half-life (t 1/2 ) of rHSA/IFNα2a was estimated to be 120-140 h, and is potentially suitable for a dosing interval of 2 weeks or longer. Pharmacokinetics of the last dose between rHSA/IFNα2a 750 μg and PEG-IFNα2a 180 μg, with the exception of t 1/2 , was comparable, and a similar kinetics of inhibiting HBV DNA replication was observed in both groups. Mean reductions in serum HBV DNA levels after treatment were À1.32, À2.13, À1.10 and À2.48 log10 IU/ml in the 600, 750 and 900 μg rHSA/IFNα2a groups and PEG-IFNα2a group, respectively. CONCLUSIONSThe rHSA/IFNα2a treatment was well tolerated and can be administered biweekly. Similar efficacy in inhibiting HBV replication was observed in both PEG-IFNα2a and rHSA/IFNα2a 750 μg groups.