A Randomized, Double-blind, Placebo-controlled, Parallel Group, 2-part Study Investigating the Effect of LIK066 on Body Weight in Dysglycemic (Prediabetes or Type 2 Diabetes) and Normoglycemic Patients With Elevated Body Mass Index
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 181
- 试验地点
- 1
- 主要终点
- Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death
研究概览
简要总结
A 12-week study to assess LIK066 effect on body weight in diabetics, prediabetics and normoglycemic patients with elevated body mass index (BMI)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •Subjects with stable health condition as determined by past medical history, physical examination, electrocardiogram, and laboratory tests at screening.
- •Patients with dysglycemia are patients with: Fasting plasma glucose >100mg/dL (5.6 mmol/L), or HbA1c > 5.7% and < 10% at screening.
- •Fasting plasma glucose ≤250mg/dL (13.9 mmol/L) at screening.
- •If treated with antidiabetic medications (other than prohibited medications), patients must be on a stable dose for 12 weeks prior to randomization and maintain the dose until the end of the study.
- •Subjects must have a body mass index (BMI) within the range of 35 - 50 kg/m2 at screening, with stable body weight (± 5 kg) within 3 months prior to screening
排除标准
- •Pre-existing, clinically significant gastrointestinal, liver, cardiovascular, renal or other chronic medical condition which is considered serious or unstable, other than stable cardiovascular disease, treated hypertension, dyslipidemia or other stable chronic disorders
- •Clinically significant GI disorder related to malabsorption or that may affect drug or glucose absorption or history of significant gastrointestinal surgery that could affect intestinal glucose absorption
- •Enrollment in a diet, weight loss or exercise programs with the specific intent of losing weight, within 3 months prior to randomization, or clinical diagnosis of any eating disorder
- •Pregnant or nursing (lactating) women, and women of child-bearing potential
研究组 & 干预措施
Part 1: LIK066 150 mg once daily (qd)
LIK066 150 mg qd within 15 minutes before starting lunch
干预措施: LIK066 (Drug)
Part 1: Placebo once daily
Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch.
干预措施: LIK066 (Drug)
Part 2: LIK066 75 mg twice daily (bid)
LIK066 75 mg bid before breakfast and dinner
干预措施: Placebo (Drug)
Part 2: LIK066 50 mg three times daily (tid)
LIK066 50 mg tid before all 3 meals;
干预措施: Placebo (Drug)
Part 2: Placebo three times daily
Matching placebo tablets tid before meals.
干预措施: LIK066 (Drug)
结局指标
主要结局
Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death
时间窗: 12 weeks
This endpoint reports patients with at least one AE (any AE), serious AE and death.
Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death
时间窗: 2 weeks
This endpoint reports patients with at least one AE (any AE), serious AE and death
Part 1: Percent Change in Body Weight From Baseline to Week 12
时间窗: Baseline, Week 12 (Day 85)
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is Day -1 in Part 1. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by- time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, and the treatment-by-time-by-glycemic status interaction, and Baseline body weight as a covariate.
Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14)
时间窗: Baseline, Week 2 (Day 14)
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Part 1: Baseline is defined as Day -1. Part 2: Baseline is defined as Day 1 predose. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate.
次要结局
- Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms(Baseline, Week 2)
- Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study(Day 84)
- The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study(Day 84)
- The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study(Day 84)
- Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study(Day 1, Day 14)
- Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study(Day 1, Day 14)
- Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study(Day 84)
- Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study(Day 84)
- Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study(Day 84)
- Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study(Day 1, Day 14)
- Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study(Day 1, Day 14)
- The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study(Day 1, Day 14)
- The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study(Day 1, Day 14)