Phase I Open Label, Drug-Drug Interaction, Study to Evaluate the Effect of Itraconazole and Phenytoin on the Pharmacokinetics of ASC41 in Healthy Volunteers and A Study to Evaluate the PK, Safety and Tolerability in Subjects With Non-alcoholic Fatty Liver Disease (NAFLD).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Cmax of ASC41
研究概览
简要总结
The primary objective of this study is to evaluate the effect of itraconazole, a strong inhibitor)of cytochrome P4503A , and phenytoin a strong inducer of cytochrome P450 3A, CYP3A4, CYP1A2 and CYP2C19 on the pharmacokinetics of ASC41, a THR beta agonist tables in healthy subjects. The PK, Safety and Tolerability of ASC 41 in Subjects with NAFLD will also be evaluated. Approximately 24 subjects including 16 healthy volunteers (HVs) and 8 subjects with NAFLD will be enrolled. This study consists of 3 cohorts.
详细描述
This multiarm study in HVs and subjects with NAFLD is designed to further characterize the PK, safety and tolerability of ASC41. Part I of the study will assess the effect of itraconazole and phenytoin on the single-dose PK of ASC41 in HVs. Part II of the study will evaluate the PK, safety and tolerability of a single dose of ASC41 in subjects with NAFLD. The pharmacokinetics of ASC41 and its metabolite ASC41-A will be assessed in both parts I and II. The secondary objective of the study is to characterize the safety and tolerability of oral ASC41 in subjects in the U.S. with NAFLD and in HVs. Approximately 24 male and female participants will be enrolled. This study consists of 3 cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part I Healthy subjects between 18 to 55 years of age
- •Subjects with NAFLD
- •Subjects between 18 to 65 years of age
- •Key Exclusion criteria:
- •A history of thyroid disease
- •A history of, or current liver disease, or liver injuries
- •Platelet count <150,000/mcL
- •History of, or current electrocardiogram (ECG) abnormalities, arrhythmias or heart valve diseases judged to be clinically significant by the investigator
- •A history of thyroid disease
- •Current or history of cirrhosis or decompensated liver disease
- •AST or ALT > 5X ULN
- •DBIL > ULN
- •Acute or chronic liver disease other than NAFLD
- •A history of bariatric surgery
- •HbA1c >9.5% at screening
- •Testosterone or estrogen replacement therapy
- •Inducers or inhibitors of CYP3A4, including herbal therapies such as St John's Wort (CYP3A4 Inducer)
排除标准
- 未提供
研究组 & 干预措施
ASC41 + Phenytoin group
- ASC41 5 mg po, One 5 mg ASC41 tablet on day 1 and 19.
- Phenytoin oral capsule 300 mg (100 mg 3 x/day) on days 6-19.
干预措施: ASC41 (Drug)
ASC41 + Itraconazole group
- ASC41 5 mg po, One 5 mg ASC41 tablet on day 1 and 11.
- Itraconazole oral capsule 200 mg po qd (2 capsules given 1x/day or 200 mg/day) on days 6-16.
干预措施: ASC41 (Drug)
ASC41 + Itraconazole group
- ASC41 5 mg po, One 5 mg ASC41 tablet on day 1 and 11.
- Itraconazole oral capsule 200 mg po qd (2 capsules given 1x/day or 200 mg/day) on days 6-16.
干预措施: Itraconazole (Drug)
ASC41 + Phenytoin group
- ASC41 5 mg po, One 5 mg ASC41 tablet on day 1 and 19.
- Phenytoin oral capsule 300 mg (100 mg 3 x/day) on days 6-19.
干预措施: Phenytoin (Drug)
ASC41 group
(1) ASC41 5 mg po. One 5 mg ASC41 tablet on day 1.
干预措施: ASC41 (Drug)
结局指标
主要结局
Cmax of ASC41
时间窗: Up to 24 days
Evaluate the Peak Plasma Concentration.
AUC of ASC41
时间窗: Up to 24 days
Evaluate the Area under the plasma concentration versus time curve.
次要结局
- t1/2 of ASC41(Up to 24 days)
- CL/F of ASC41(Up to 24 days)
- Vd/F of ASC41(Up to 24 days)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 24 days)