|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30441
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
APASL2017[PP0170]
Multiple dose study of GLS4JHS, interfering with the assembly
of HBV core particles, in patients infected with hepatitis B virus
Hong Zhang1, Junqi Niu1, Yanhua Ding1, Hong Chen1, Yue Hu1,
Lin Luo2, Yingjun Zhang2, Cuiyun Li1, Xiaojiao Li1, Liu Jingrui1,
Fengjiao Wang1, Min Wu1, Haijing Wei1, Jixuan Sun1, Meng
Wang1, Guiling Chen1
1Phase I Clinical Research Center, The First Hospital of Jilin
University, Changchun; 2HEC R&D Center, HEC Pharm Co., Ltd.,
Dongguan
Background: GLS4JHS can interfere with the assembly of hepatitis
B virus (HBV) core particles and is a new generation of two hydrogen
pyrimidine antiviral drug. Its structure and anti-HBV mechanism are
similar to Bay41-4109. Because of the short half-life of GLS4JHS, its
effect is affected. Ritonavir can inhibit hepatic enzymes to improve
the exposure of GLS4JHS, reduce the dosage and frequency and
improve the anti-HBV effect. The antiviral activity, resistance profile,
pharmacokinetics (PK), safety, and tolerability of combination of
GLS4JHS and ritonavir, were evaluated in a double-blind, placebocontrolled,
sequential panel, multiple dose study.
Methods: Twenty-four patients with HBV infection were randomized
to receive a 28-day course of combination of GLS4JHS (120 mg QD,
240 mgQD) and Ritonavir (100 mg QD) or entecavir in a ratio of
1:1:1. The antiviral activity, resistance profile, pharmacokinetics
(PK), safety, and tolerability were assessed in the study.
Result: The mean decline from baseline in HBV DNA was 2.37
(0.08–4.78) log 10 IU/mL and the mean decline in HBsAg was 9601
IU/mL after 28 days treatment (Data of subjects in entecavir group
was included). Most patients experienced viral rebound after termination
of the treatment. The PK profile was supportive of once-daily
dosing with mean peak plasma concentrations at 2.5 h postdose and
mean terminal half-life of 64.3 h after last dosage in 120 mg group.
Steady state was achieved following 6 days of daily dosing. The
accumulation rate was similar among the different groups
(1.64–1.98), which indicates that the accumulation is low. The relationship
between GLS4JHS exposures (AUC and Cmax) and dosage
were not linear and the slopes were 0.55 and 0.84, respectively.
GLS4JHS was tolerated in all dose groups. Most of the adverse events
were mild and recovered or improved without treatment. There were
no significant clinically relevant changes in vital signs, laboratory, or
electrocardiogram parameters.
Conclusion: The combination of GLS4JHS and Ritonavir was well
tolerated and produced a rapid and substantial decrease in HBV-DNA
levels in patients chronically infected with HBV. On the basis of these
results, GLS4JHS 120 mg was recommended for further evaluation in
phase II trials.
|
|
发表于 2017-2-18 23:19
