A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Ranolazine When Added to Metformin in Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 442
- 试验地点
- 142
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to determine the effect of ranolazine when added to metformin on glycemic control in adults with type 2 diabetes mellitus (T2DM) who are inadequately controlled despite current treatment with stable metformin therapy in addition to diet and exercise.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented history of T2DM
- •Metformin therapy at a stable total daily dose ≥ 1500 mg and ≤ 2550 mg in addition to diet and exercise for ≥ 8 weeks prior to Screening
- •Body mass index (BMI) 25 to 45 kg/m^2, inclusive, at Screening
- •HbA1c within specified ranges at Screening and at the end of the Qualifying Period based on current metformin dose
- •C-peptide ≥ 0.8 ng/mL at Screening
- •Fasting serum glucose (FSG) ≥ 130 mg/dL (7.2 mmol/L) and ≤ 240 mg/dL (13.3 mmol/L) at Screening and at the end of the Qualifying Period
排除标准
- •Type 1 diabetes mellitus
- •History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
- •History of severe hypoglycemia
- •Any clinically significant cardiovascular or cerebrovascular event ≤ 3 months prior to Screening
- •History of congestive heart failure
- •Corrected QT interval (QTc) > 500 msec by ECG at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or individuals who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
- •Serum creatinine concentration ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females at Screening
- •Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase (AST) > 3 x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3 x ULN and/or serum total bilirubin > 2.0 mg/dL
- •Use of any non-insulin antihyperglycemic therapy (other than metformin) for more than 14 days (consecutive or not) during the 12 weeks (24 weeks for thiazolidinediones) prior to Screening and/or use of any antihyperglycemic therapy other than metformin, at any dose, at any time during the 4 weeks prior to randomization
- •Treatment with chronic insulin within 24 weeks prior to Screening (except for one temporary period of daily insulin injections no longer than 7 days)
- •Treatment with strong or moderate cytochrome P450 3A (CYP3A) inhibitors or P-glycoprotein (P-gp) inhibitors within 14 days prior to randomization
- •Treatment with CYP3A inducers or P-gp inducers within 14 days prior to randomization
- •Treatment with simvastatin or lovastatin at a dose > 20 mg or > 40 mg daily, respectively, within 14 days prior to randomization
研究组 & 干预措施
Ranolazine+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Ranolazine (Drug)
Ranolazine+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Metformin (Drug)
Ranolazine+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Placebo to match metformin (Drug)
Ranolazine+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Diet (Behavioral)
Ranolazine+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Exercise (Behavioral)
Placebo+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Placebo to match ranolazine (Drug)
Placebo+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Metformin (Drug)
Placebo+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Diet (Behavioral)
Placebo+metformin
Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).
Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24.
Participants are required to maintain their diet and exercise regimen.
干预措施: Exercise (Behavioral)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
时间窗: Baseline; Week 24
The average (mean) change from baseline in HbA1c at Week 24 was analyzed.
次要结局
- Change From Baseline in Fasting Serum Glucose at Week 24(Baseline; Week 24)
- Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24(Baseline; Week 24)