A Randomized, Double-Blind, Placebo-Controlled, Double-Dummy, Parallel Group, Multicenter, Dose-Ranging Study in Subjects With Type 2 Diabetes Mellitus to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered SGLT2 Inhibitor JNJ-28431754 With Sitagliptin as a Reference Arm
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 451
- 主要终点
- Change in HbA1c From Baseline to Week 12
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness, safety, and tolerability of JNJ-28431754 compared with placebo in patients with type 2 diabetes.
详细描述
Type 2 diabetes mellitus is a metabolic disorder that is characterized by decreased secretion of insulin by the pancreas and resistance to the action of insulin in various tissues (muscle, liver, and adipose), which results in impaired glucose uptake. Chronic hyperglycemia leads to progressive impairment of insulin secretion and to insulin resistance of peripheral tissues in diabetes (so-called glucose toxicity), which further worsens control of blood glucose. In addition, chronic hyperglycemia is a major risk factor for complications, including heart disease, retinopathy, nephropathy, and neuropathy. Although numerous treatments have been developed for the treatment of diabetes and individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients with diabetes. This is a randomized, double-blind, placebo-controlled, parallel group, multicenter, dose-ranging study to determine the efficacy, safety and tolerability of JNJ-28431754 taken orally over 12 weeks, compared with placebo, in the treatment of Type 2 diabetes mellitus. The primary clinical hypothesis is that JNJ-28431754 is superior to placebo as measured by the change in hemoglobin A1c from baseline through Week 12 in the treatment of type 2 diabetes mellitus. Subject safety will be monitored throughout the study using spontaneous adverse event reporting, clinical laboratory tests (hematology, serum chemistry, urinalysis); severe and serious hypoglycemic episodes, assessment of urinary albumin excretion and markers of proximal renal tubular function; pregnancy tests; electrocardiograms (ECGs); vital sign measurements; physical examinations, assessment of calcium and phosphate homeostasis, bone formation and resorption markers, and hormones regulating calcium and phosphorus homeostasis; and vaginal and urine sample collection for fungal and bacterial culture in subjects with symptoms consistent with vulvovaginal candidiasis (VVC) or urinary tract infection (UTI).
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 65 Years（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
- •Hemoglobin A1c levels >=7% and <=10.5%
- •taking a stable daily dose of metformin
- •Body mass index (BMI) 25 to 45 kg/m2 except those of Asian descent who must have a BMI of 24 to 45 kg/m2
- •Stable body weight
- •Serum creatinine <=1.5 mg/dL (132.6 umol/L) for men and <=1.4 mg/dL (123.76 umol/L) for women
排除标准
- •Patients must not have prior exposure or known contraindication or suspected hypersensitivity to canagliflozin (JNJ-28431754)
- •Known contraindication or suspected hypersensitivity to sitagliptin or metformin
- •A history of diabetic ketoacidosis or type 1 diabetes mellitus
- •History of pancreas or beta-cell transplantation
- •History of active proliferative diabetic retinopathy
- •History of hereditary glucose-galactose malabsorption or primary renal glucosuria
研究组 & 干预措施
Canagliflozin 50 mg daily
Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Canagliflozin (JNJ-28431754) (Drug)
Canagliflozin 50 mg daily
Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Placebo (Drug)
Canagliflozin 100 mg daily
Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Canagliflozin (JNJ-28431754) (Drug)
Canagliflozin 100 mg daily
Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Placebo (Drug)
Canagliflozin 200 mg daily
Each patient will receive 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Canagliflozin (JNJ-28431754) (Drug)
Canagliflozin 200 mg daily
Each patient will receive 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Placebo (Drug)
Canagliflozin 300 mg daily
Each patient will receive 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo capsule once daily (in the evening).
干预措施: Canagliflozin (JNJ-28431754) (Drug)
Canagliflozin 300 mg daily
Each patient will receive 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo capsule once daily (in the evening).
干预措施: Placebo (Drug)
Canagliflozin 300 mg twice daily
Each patient will receive 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
干预措施: Canagliflozin (JNJ-28431754) (Drug)
Sitagliptin 100 mg daily
Each patient will receive 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Sitagliptin (Drug)
Sitagliptin 100 mg daily
Each patient will receive 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
干预措施: Placebo (Drug)
Placebo
Each patient will receive matching placebo twice daily for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in HbA1c From Baseline to Week 12
时间窗: Day 1 (Baseline) and Week 12
The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
次要结局
- Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12(Day 1 (Baseline) and Week 12)
- Percentage of Patients With Symptoms of Hypoglycemia(Up to Week 12)
- Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12(Day 1 (Baseline) and Week 12)
- Absolute Change in Body Weight From Baseline to Week 12(Day 1 (Baseline) and Week 12)
- Percent Change in Body Weight From Baseline to Week 12(Day 1 (Baseline) and Week 12)