A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy of LCQ908 on Cardiovascular Risk
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1)
研究概览
简要总结
This is a study designed to evaluate the potential for the pradigastat (LCQ908) to impact cardiovascular risk.
详细描述
This study had 2 parts. Part A was a multicenter, double-blind, randomized, placebo-controlled, non-confirmatory crossover study assessing response to a high-fat meal challenge in the setting of pradigastat versus placebo. Part A had 2 cohorts i.e. Cohort 1 patients with stable coronary artery disease and hypertriglyceridemia and Cohort 2 patients with asymptomatic non-obstructive coronary artery disease or elevated coronary heart disease risk and hypertriglyceridemia.
Part B was a double blinded phase designed to assess response to three months of chronic treatment with pradigastat versus placebo on a normal diet.
The trial was terminated after the interim analysis of Part A, Cohort 1. The interim analysis results indicated that the high-fat meal challenge did not induce any impairment on either myocardial perfusion reserve index (MPRi) or exercise treadmill performance. Part B was never started.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of coronary artery disease
- •Elevated triglycerides
- •On medication to help lower cholesterol
排除标准
- •Poorly controlled diabetic patients and/or change in diabetic medication within 12 weeks of screening
- •History of myocardial infarction (heart attack) within 6 months of screening
- •History of a procedure to open a blocked coronary artery within 12 months of enrollment
- •History of Coronary Artery Bypass Graft (CABG) surgery
- •History of congestive heart failure
- •History of significant heart valve disease
研究组 & 干预措施
Pradigastat (LCQ908) followed by placebo
Pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment
干预措施: pradigastat (LCQ908) (Drug)
Pradigastat (LCQ908) followed by placebo
Pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment
干预措施: Placebo (Drug)
Placebo followed by pradigastat (LCQ908)
Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by p20 mg (2 x 10-mg tablets) daily for two days
干预措施: pradigastat (LCQ908) (Drug)
Placebo followed by pradigastat (LCQ908)
Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by p20 mg (2 x 10-mg tablets) daily for two days
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1)
时间窗: Baseline, and on day 5 of each of the two treatment periods
MPRi (myocardial perfusion reserve index) is a measure of coronary microvascular function. Myocardial perfusion scans using 0.05 mmol/kg of gadolinium contrast were acquired at rest and under stress (pharmacological stress induced with adenosine 140 μg/kg/min for three minutes). An independent central reader performed the cardiac image analysis of all time points including the calculation of the myocardial perfusion reserve index from the ratio of the global stress myocardial blood flow divided by the resting blood flow values. Higher/increased index indicates improved flow/better outcome. This primary endpoint was only for Part A, Cohort 1 patients.
Aortic Plaque Inflammation (Part B)
时间窗: Baseline and on treatment day 85 +/- 3 days
This endpoint was palnned for analysis on Part B patients which was never started becasue study got terminated on Part A interim analysis.
Time to Onset of Angina (Part A, Cohort 1)
时间窗: Baseline and on day 5 of each of the two treatment periods
Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the patient and recorded by the performing investigator.
Change From Baseline in Total Exercise Duration (Part A, Cohort 1)
时间窗: Baseline and on day 5 of each of the two treatment periods
Total exercise duration was the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue. This primary endpoint was only for Part A, Cohort 1 patients.
Time to Onset of Exercise-induced Ischemia(Part A, Cohort 1)
时间窗: Baseline and on day 5 of each of the two treatment periods
Exercise-induced ischemia was defined as the new development of horizontal or down-sloping ST-segment depression (≥ 1mm at 60 milliseconds after the J point) versus baseline tracings.
次要结局
- Adiponectin Level ( Part B)(Part B; Baseline, day 15, day 43 and day 85)
- Other Related Lipid Parameters (Part A)(Baseline, day 4 and day 5 of each treatment period)
- Postprandial Triglycerides (Part A, Cohort 2)(0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5)
- Number of Participants With Adverse Events (Part A, Cohort 2)(approximately 40 days)
- Interleukin-6 (IL-6) Level (Part A)(Baseline, day 4 and day 5, of each treatment period)
- C-reactive Protein (CRP) Level (Part A)(Baseline, day 4 and day 5, of each treatment period)
- Postprandial Triglycerides (Part A, Cohort 1)(0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5)
- Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A)(Part A: Day 4 and day 5 of each treatment period)
- Number of Participants With Adverse Events (Part A, Cohort 1)(approximately 40 days)