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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(6): 1304-1308

Tolerance and pharmacokinetics of coblopasvir hydrochloride capsules in patients with hepatitis C virus infection

DOI: 10.3969/j.issn.1001-5256.2021.06.018
  • 1a.

    Eighth Treatment Zone of Department of Cadre Ward, The First Hospital of Jilin University, Changchun 130021, China

  • 1b.

    Department of Phase I Clinical Trial, The First Hospital of Jilin University, Changchun 130021, China

  • 1c.

    Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, China

  • 2.

    Beijing Kawin Technology Share-Holding Co., Ltd., Beijing 100176, China

  • Received Date: 2020-11-10
  • Accepted Date: 2020-12-11
  • Published Date: 2021-06-20
    Abstract
  •   Objective  To investigate the tolerance, pharmacokinetics, and antiviral activity of coblopasvir hydrochloride capsules in patients with hepatitis C.  Methods  A total of 36 patients with hepatitis C who were admitted to The First Hospital of Jilin University from November 2016 to January 2017 were enrolled as subjects, and four dose groups (30 mg, 60 mg, 90 mg, and 120 mg) and one placebo group were established. The subjects were administered once daily for 3 consecutive days; tolerance was evaluated on D2 and D6, and follow-up was performed on D8 and D10. The subjects were enrolled based on single dose escalation, and a multiple-dose study was conducted under the premise of good tolerance to single dose. Liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of coblopasvir hydrochloride in human body, and WinNonlin 6.4 software was used to calculate main pharmacokinetic parameters. HCV RNA load was used to evaluate antiviral activity at different time points; a one-way analysis of variance was used for comparison between multiple groups, and the LSD t-test was used for further comparison between two groups.  Results  After coblopasvir hydrochloride capsules were administered orally once a day at a dose of 30-120 mg, the plasma concentration and exposure of coblopasvir hydrochloride increased with the increase in dose. There were no significant differences in plasma concentration and exposure between multiple-dose administration and single-dose administration in a fasting state, without accumulation in human body. After the oral administration of coblopasvir hydrochloride capsules once a day, the subjects with HCV genotype 1b had a reduction in HCV RNA load since baseline, with the lowest level at 120 hours, and there was a significant difference in antiviral activity between different dose groups (F=14.621, P < 0.000 1), among which the 60 mg group had a significantly greater reduction than the 30 mg group (P=0.025), while there was no significant difference between the 60 mg group and the 90/120 mg group (P > 0.05). There was no significant difference in HCV RNA load between different groups of patients with HCV genotype 2a (P > 0.05). Of all 36 subjects, 20 reported 34 cases of treatment-emergent adverse events, among which 19 cases were associated with coblopasvir hydrochloride, and no significant adverse events or serious adverse events were observed.  Conclusion  Oral administration of coblopasvir hydrochloride capsules in a fasting state at a dose of 30-120 mg/d (for 3 consecutive days) has good safety and antiviral activity. Therefore, it has good application prospect in the treatment of HCV infection and provides a basis for dose selection in phrase 2 study.

     

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    • References(5)
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