A Multi-center, Randomized, Double-blind, Parallel-group Dose-finding Study to Assess the Effect of 3 Doses of LIK066 Compared to Placebo or Empagliflozin in Type 2 Diabetes Mellitus Patients With Heart Failure
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 125
- 试验地点
- 1
- 主要终点
- Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 12
研究概览
简要总结
This was a dose-finding study to evaluate the efficacy, safety and tolerability of 3 different doses of LIK066 compared to placebo or empagliflozin in T2DM patients with heart failure
详细描述
The study was prematurely discontinued on 04-May-2018 due to slow enrollment that would preclude obtaining study results in a timely manner.
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
- •BMI ≥ 22kg/m^2
- •Type 2 diabetes with HbA1c between 6.5% and 10.0%
- •Documented symptomatic chronic heart failure (NYHA II-IV)
- •Plasma NT-proBNP > 300pg/ml
- •eGFR ≥ 45ml/min/1.73m^2 (calculated by MDRD)
排除标准
- •Pregnant or nursing (lactating) women
- •Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes
- •History of ketoacidosis, lactic acidosis, or hyperosmolar coma
- •Symptomatic genital infection or UTI within 4 weeks of screening
- •Myocardial infarction, stroke, surgery for heart disease, percutaneous coronary intervention within 3 months of randomization
- •Unstable angina within 3 months of screening
- •Isolated right HF due to pulmonary disease
- •Patients with a mean sitting systolic blood pressure ≤ 100mmHg, at randomization
- •History of lower limb amputation
- •Diabetic foot ulcer at screening
研究组 & 干预措施
LIK066 2.5mg
Eligible participants randomized to this treatment arm received the LIK066 2.5mg dose regimen once daily for 36 weeks.
干预措施: LIK066 (Drug)
LIK066 10mg
Eligible participants randomized to this treatment arm received the LIK066 10mg dose regimen once daily for 36 weeks.
干预措施: LIK066 (Drug)
LIK066 50mg
Eligible participants randomized to this treatment arm received the LIK066 50mg dose regimen once daily for 36 weeks.
干预措施: LIK066 (Drug)
Empagliflozin
Participants randomized to this treatment arm received empagliflozin once daily for 36 weeks.
干预措施: Empagliflozin (Drug)
Placebo
Participants randomized to this treatment arm received LIK066 matching placebo and empagliflozin matching placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 12
时间窗: Baseline, Week 12
Evaluation of NT-proBNP was performed by a central laboratory. For Change from baseline, Geometric mean is the geometric mean of the endpoint to baseline ratio. Pre-planned statistical analysis was not performed for this primary endpoint due to early study termination. Only descriptive statistics are presented.
次要结局
- Change From Baseline in Body Composition Assessed by Bio-impedance (Lean Body Mass) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Composition Assessed by DXA (Total Body Fat Mass) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Composition Assessed by DXA (Lean Body Mass) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Fasting Lipid Profile (Triglycerides (TG)) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Fasting Lipid Profile (Lipoproteins) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Fasting Lipid Profile (Total Cholesterol) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in 24 Hour Sodium Excretion at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Composition Assessed by Bio-impedance (Visceral Fat Level) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 36(Baseline, Week 36)
- Change From Baseline in Glycated Hemoglobin (HbA1c) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Weight at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Composition Assessed by Bio-impedance (Total Body Fat Mass) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Composition Assessed by DXA (Visceral Fat Mass) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Body Composition Assessed by DXA (Total Body Water) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Sitting Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in High Sensitive C-reactive Protein (hsCRP) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in 24 Hour Urinary Glucose Excretion (UGE) at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at Week 12 and 36(Week 12, Week 36)
- 24 Hour Urinary Phosphate Excretion at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Left Atrial Size at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Left Atrial Volume at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Number of Participants With New York Heart Association (NYHA) Class I, II, II or IV(Baseline, Week 12, Week 36)
- Change From Baseline in 24 Hour Urinary Calcium Excretion at Weeks 12 and 36(Baseline, Week 12, Week 36)
- Change From Baseline in Bone Mineral Density (BMD) at Weeks 12 and 36(Baseline, Week 12, Week 36)