A Randomized, Double-Blind, 5-Arm, Parallel-Group, 26-Week, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in Combination With Metformin as Initial Combination Therapy in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,186
- 主要终点
- Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26
研究概览
简要总结
The purpose of this study is to assess the effectiveness of the co-administration of canagliflozin and metformin extended release (XR) compared with canagliflozin alone, and metformin XR alone in patients with type 2 diabetes mellitus with inadequate control despite treatment with diet and exercise. The safety and tolerability of canagliflozin will also be assessed.
详细描述
This study will be a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), active-controlled (one of the treatments is an established effective treatment for type 2 diabetes mellitus), parallel-group (each group of participants will be treated at the same time), 5-arm (groups), multicenter study. Approximately 1,200 participants will be randomly assigned to the 5 treatment arms in a 1:1:1:1:1 ratio for 26 weeks.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have type 2 diabetes mellitus with inadequate glycemic control on diet and exercise
- •Not on antihyperglycemic agent therapy (at least 12 weeks before screening) and have a screening visit fingerstick glycated hemoglobin (HbA1c) of more than or equal to 7 percent and less than or equal to 12.5 percent
- •Have a screening visit HbA1c of more than or equal to 7.5 percent and less than or equal to 12 percent as determined by the central laboratory
- •Must have a fasting plasma glucose of less than or equal to 300 mg/dL (16.7 mmol/L) prior to randomization
- •Must have a fasting fingerstick glucose of greater than 120 mg/dL (6.7 mmol/L) performed at home or at the study center prior to randomization
排除标准
- •History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
- •Fasting C-peptide less than 0.70 ng/mL (0.23 nmol/L) in participants for whom the investigator cannot reasonably exclude T1DM based upon clinical evaluation
- •Repeated (2 or more over a 1 week period) fasting self-monitored blood glucose measurements more than 300 mg/dL (16.7 mmol/L) prior to randomization, despite reinforcement of diet and exercise counseling
- •History of hereditary glucose-galactose malabsorption or primary renal glucosuria
- •Has history of, or currently active, illness considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results
研究组 & 干预措施
Canagliflozin 100 mg
Participants will receive one 100 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
干预措施: Canagliflozin 100 mg (Drug)
Canagliflozin 300 mg
Participants will receive one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.
干预措施: Canagliflozin 300 mg (Drug)
Metformin XR
Participants will receive metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks.
干预措施: Metformin XR (Drug)
Canagliflozin 100 mg + Metformin XR
Participants will receive one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
干预措施: Canagliflozin 100 mg (Drug)
Canagliflozin 100 mg + Metformin XR
Participants will receive one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
干预措施: Metformin XR (Drug)
Canagliflozin 300 mg + Metformin XR
Participants will receive one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
干预措施: Canagliflozin 300 mg (Drug)
Canagliflozin 300 mg + Metformin XR
Participants will receive one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.
干预措施: Metformin XR (Drug)
结局指标
主要结局
Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26
时间窗: Day 1 (Baseline) and Week 26
The change in the value of glycated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) from baseline at Week 26 was compared between the different treatment groups.
次要结局
- Percent Change in Body Weight From Baseline to Week 26(Day 1 (Baseline) and Week 26)
- Percentage of Participants With Glycated Hemoglobin (HbAIc) Less Than 7 Percent at Week 26(Week 26)
- Change in Systolic Blood Pressure From Baseline at Week 26(Day 1 (Baseline) and Week 26)
- Percent Change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26(Day 1 (Baseline) and Week 26)
- Percent Change in Triglycerides From Baseline to Week 26(Day 1 (Baseline) and Week 26)
- Number of Participants With Treatment Emergent Adverse Events (AEs)(Up to 30 weeks of last study drug administration)