A 12-week Randomized, Patient and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate the Efficacy of LIK066 in Obese Patients With Non-alcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 1
- 主要终点
- Change From Baseline in Alanine Aminotransferase (ALT) at Week 12
研究概览
简要总结
The purpose of this study was to assess the effects of LIK066 on a variety of metabolic and inflammation biomarkers in patients with non-alcoholic steatohepatitis (NASH)
详细描述
This was a a non-confirmatory, multicenter, patient and investigator blinded, randomized, placebo-controlled, parallel group study in patients with non-alcoholic steatohepatitis (NASH).
The study consisted of a 28 day screening period (Day -44 to Day -16), a baseline period of 14 days (Day -15 to Day -1), a treatment period of 12 weeks (Day 1 to Day 84), and a study completion evaluation approximately 28 days after the last drug administration. The patients were advised to maintain their recommended diet during the study.
Patients who met the inclusion/exclusion criteria at screening went to the study site for baseline assessments. All baseline safety evaluation results were available prior to the first dosing.
The study started by enrolling patients into the 150 mg and placebo arms with a randomization ratio of 2:1. After the enrollment of the first 33 patients, the 30 mg arm was added to the study and the randomization ratio changed to a 2:4:1 ratio (150 mg: 30 mg: placebo) to maintain the 2:2:1 ratio across the three groups (150 mg: 30 mg: placebo) at study completion.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening.
- •Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening:
- •ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND
- •BMI greater than or equal to 27 kg/m^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m^2 (in patients with a self identified Asian race) AND
- •Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10%
- •Patients must weigh no more than 150 kg (330 lbs) to participate in the study.
- •Male and female patients 18 years or older at the time of screening visit.
排除标准
- •History or presence of other concomitant liver diseases
- •History or current diagnosis of ECG abnormalities
- •Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study
- •Patients with contraindications to MRI imaging
- •Current or history of significant alcohol consumption
- •Clinical evidence of hepatic decompensation or severe liver impairment
- •Women of child bearing potential (unless on basic contraception methods)
- •Presence of liver cirrhosis
研究组 & 干预措施
LIK066 30 mg
Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
干预措施: LIK066 (Drug)
LIK066 150 mg
Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84
干预措施: LIK066 (Drug)
Placebo
LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Alanine Aminotransferase (ALT) at Week 12
时间窗: Baseline, Week 12
Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.
次要结局
- Percent Change From Baseline in Total Body Weight at Week 12(Baseline, Week 12)
- Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.(Baseline, Week 12)
- Change From Baseline in Percent Liver Fat at Week 12(Baseline, Week 12)
- Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12(Baseline, Week 12)
- Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.(Baseline, Week 12)
- Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12.(Baseline, Week 12)
- Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration(Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose))
- Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration(Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose))
- Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration(Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose))
- Change From Baseline in Aspartate Aminotransferase (AST) at Week 12(Baseline, Week 12)