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J Pharm Pharmacol. 2018 Jul;70(7):855-864. doi: 10.1111/jphp.12916. Epub 2018 Apr 6.

Clinical evaluation of efficacy, tolerability and pharmacokinetics of yimitasvir phosphate in patients infected with hepatitis C virus.

Author information

1
Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
2
The First Hospital of Jilin University, Jilin, China.

Abstract

OBJECTIVE:

Yimitasvir phosphate, an inhibitor of nonstructural protein 5A (NS5A) replication complex of hepatitis C virus (HCV), was evaluated in a double-blind, placebo-controlled, parallel, multiple-dose study.

METHODS:

Twenty-four patients with chronic HCV genotype 1 infection were randomized to receive a 7-day course of yimitasvir phosphate at daily doses of 30, 100 or 200 mg or placebo. Antiviral efficacy, resistance profile, pharmacokinetics (PK), safety and tolerability were assessed.

KEY FINDINGS:

The maximal reduction in HCV RNA from baseline was 5.17 log10 IU/ml. However, most patients experienced viral rebound on or before day 3 after yimitasvir treatment was initiated. The PK profile revealed median peak plasma concentrations at 4-12 h postdose and a mean terminal half-life of 14.47-17.09 h, the basis for daily dosing. Steady drug state was achieved following 5 days of daily dosing. The accumulation rate was low (1.29-1.73). There were no significant alterations in vital signs and laboratory findings among all participants.

CONCLUSIONS:

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.

KEYWORDS:

direct-acting antiviral agent; genotype 1; hepatitis C; nonstructural protein 5A; pharmacokinetics

PMID:
29630721
DOI:
10.1111/jphp.12916
[Indexed for MEDLINE]

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