A Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group, 24-week Pilot Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in Patients With Non-alcoholic Fatty Liver Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24
研究概览
简要总结
The purpose of this study was to determine whether LCQ908 effectively lowers liver fat, as assessed by MRI and to assess its safety and tolerability profile in subjects with non-alcoholic fatty liver disease (NAFLD).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of liver steatosis during the preceding 24 months
- •History of fasting TGs > 200 mg/dL (confirmed at screening).
- •Liver fat ≥ 10% as determined by the central MRI laboratory.
- •Subjects on the following medications can be included if these medications are medically necessary, cannot be stopped and the investigator feels their dose will remain stable for the duration of the double-blind treatment period:
- •Stable dose of anti-diabetic medications (metformin and/or sulfonylureas) for at least 8 weeks prior to screening.
- •Stable doses of beta-blockers and thiazide diuretics for at least 8 weeks prior to screening.
- •Stable doses of fibrates, statins, niacin, ezetimibe for at least 8 weeks prior to screening.
- •Stable dose of vitamin E in patients taking >200 IU/day for at least 6 months prior to screening.
排除标准
- •Treatment with omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements > 200 mg per day within 8 weeks of screening.
- •Treatment with antiretrovirals, tamoxifen, methotrexate, cyclophosphamide, isotretinoin, bile acid binding resins or pharmacologic doses of oral glucocorticoids (≥10 mg of prednisone per day or equivalent) within 8 weeks of screening.
- •ALT or AST > 250 IU/L at the time of screening.
- •History/current evidence of heavy alcohol use or alcoholism (> 21 drinks per week in men and > 14 drinks per week in women) over a 2-year period prior to screening.
- •Presence of chronic liver disease, such as chronic hepatitis B and/or C, alcoholic liver disease, hemochromatosis, Wilson's disease, known cirrhosis.
- •Platelet count <150,000 at screening.
- •BMI >45 Kg/m
- •Other protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Placebo
Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
干预措施: placebo (Drug)
pradigastat (LCQ908) 5mg/10mg
Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
干预措施: LCQ908 (Drug)
pradigastat (LCQ908) 10mg/20mg
Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
干预措施: LCQ908 (Drug)
结局指标
主要结局
Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24
时间窗: From baseline to week 24
Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).
次要结局
- Percentage of Patients With Normalized Liver Enzymes(Baseline, week 6, week 12 and week 24)
- Percentage of Responders at Week 12(At week 12)
- Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24(From Baseline to week 24)
- Percent Change From Baseline in Fasting Triglycerides(Baseline, 6, 12 and 24 weeks)
- Change From Baseline in Waist Circumference(Baseline, 12 and 24 weeks)
- Post-prandial Peak Triglycerides Over 0 - 8 Hours(Baseline, 6 and 24 weeks)
- Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12(From baseline to week 12)
- Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12(From Baseline to week 12)
- Percentage of Responders at Week 24(From baseline to week 24)
- Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6(From Baseline to week 6)
- Change From Baseline in Body Weight(Baseline, 12 and 24 weeks)
- Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability(24 weeks)