A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,330
- 主要终点
- Major Adverse Cardiovascular Events (MACE) Composite of Cardiovascular (CV) Death, Non-Fatal Myocardial Infarction (MI), and Non-Fatal Stroke
研究概览
简要总结
The study will assess canagliflozin (JNJ-28431754) in the treatment of patients with type 2 diabetes mellitus (T2DM) with regard to cardiovascular (CV) risk for major adverse cardiac events (MACE). Other objectives include evaluating the overall safety, tolerability, and effectiveness of canagliflozin.
The data from this study will be combined with the data from CANVAS-R study (Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects with T2DM, NCT01989754) in a pre-specified integrated analysis of CV safety outcomes to satisfy US FDA post-marketing requirements for canagliflozin.
详细描述
The study will evaluate canagliflozin compared to placebo on CV events including CV death, heart attack, and stroke in patients with T2DM, whose diabetes is not well controlled at the beginning of the study and who have a history of CV events or have a high risk for CV events. The study includes 3 substudies which will compare the effectiveness of lowering blood glucose and assess the safety of canagliflozin relative to placebo in patients receiving specific commonly-used diabetes agents. 4,330 participants will be randomly assigned to treatment with 1 of 2 doses of canagliflozin (100 or 300 mg) or placebo, in a 1:1:1 ratio. This study was originally designed to last for up to 9 years. As per FDA post-marketing requirements for canagliflozin, the study's last subject last visit will now occur when enough MACE events (ie, CV death, nonfatal myocardial infarction, nonfatal stroke) are accumulated between the CANVAS (this study) and CANVAS-R studies. The completion target was reached in February 2017.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a diagnosis of type 2 diabetes mellitus and greater than or equal to (>=) 30 yrs old with history of cardiovascular (CV) event, or >= 50 yrs old with high risk of CV events
- •Patients must have inadequate diabetes control (as defined by glycosylated hemoglobin greater than or equal to 7.0% to less than or equal to 10.5% at screening) and be either (1) not currently on diabetes drug therapy or (2) on therapy with any approved class of diabetes drugs
排除标准
- •A history of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
- •History of one or more severe hypoglycemic (ie, very low blood sugar) episode within 6 months before screening
研究组 & 干预措施
Placebo
Each patient will receive placebo (inactive medication) on background standard of care for diabetes once daily for the duration of the study
干预措施: Placebo (Drug)
Canagliflozin (JNJ-28431754) 100 mg
Each patient will receive canagliflozin (JNJ-28431754) 100 mg once daily on background standard of care for diabetes once daily for the duration of the study
干预措施: Canagliflozin (JNJ-28431754) 100 mg (Drug)
Canagliflozin (JNJ-28431754) 300 mg
Each patient will receive canagliflozin (JNJ-28431754) 300 mg once daily on background standard of care for diabetes once daily for the duration of the study
干预措施: Canagliflozin (JNJ-28431754) 300 mg (Drug)
结局指标
主要结局
Major Adverse Cardiovascular Events (MACE) Composite of Cardiovascular (CV) Death, Non-Fatal Myocardial Infarction (MI), and Non-Fatal Stroke
时间窗: Up to approximately 8 years
MACE, defined as a composite of CV death, non-fatal MI, and nonfatal stroke. Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.
次要结局
- Percentage of Participants With Progression of Albuminuria at the End-of-Treatment(End of treatment (approximately 338 weeks))
- Percent Change From Baseline in Body Weight at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Triglycerides Levels at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) to High-Density Lipoprotein-Cholesterol (HDL-C) Ratio at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Homeostasis Model Assessment 2 Steady-State Beta-Cell Function (HOMA2-%B) at the End-of-Treatment (EOT)(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at the End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Urinary Albumin/Creatinine Ratio at End-of-Treatment(Baseline and End of treatment (approximately 338 weeks))
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Glycated Hemoglobin (HbA1c) at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))
- Change From Baseline in Fasting Plasma Glucose (FPG) Levels at End-of-Treatment(Baseline and end of treatment (approximately 338 weeks))