A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin 10 mg in Combination With Metformin as Initial Therapy as Compared With Dapagliflozin 10 mg Monotherapy and Metformin Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 1,093
- 试验地点
- 64
- 主要终点
- Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 (Last Observation Carried Forward) - Randomized Treated Participants
研究概览
简要总结
The primary purpose of this study is to compare the change from baseline in hemoglobin A1C achieved with dapagliflozin 10 mg in combination with metformin XR as compared with metformin XR monotherapy and compared with Dapagliflozin monotherapy, after 24 weeks of oral administration of double-blind treatment. The safety of treatment with dapagliflozin will also be assessed in this study
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 77 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment naive males and females, >= 18 years old and
- •<= 77 years old, with type 2 diabetes mellitus
- •Subjects must have central laboratory pre-randomization hemoglobin A1C >= 7.5 and <= 12.0%
- •C-peptide >= 1.0 ng/mL (0.34 nmol/L)
- •Body Mass Index <= 45 kg/m2
- •Must be able to perform self monitoring of blood glucose
排除标准
- •aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3X*upper limit of normal (ULN)
- •Serum Total bilirubin >2 mg/dL (34.2 µmol/L)
- •Creatinine kinase >3*ULN
- •Serum creatinine >= 1.50 mg/dL (133 µmol/L) for male subjects, >= 1.40 mg/dL (124 µmol/L) for female subjects
- •Calcium value outside of the central laboratory normal reference range
- •Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases
- •Urine albumin:creatinine ratio (UACR) >1800 mg/g (203.4 mg/mmol Cr)
- •Severe uncontrolled hypertension defined as systolic blood pressure (SBP) >=180 mmHg and/or diastolic blood pressure (DBP) >=110 mmHg
- •Hemoglobin >=11.0 g/dL (110 g/L) for men; hemoglobin >=10.0 g/dL (100 g/L) for women
- •Positive for hepatitis B surface antigen
- •Positive for anti-hepatitis C virus antibody
- •History of diabetes insipidus
- •History of diabetic ketoacidosis or hyperosmolar nonketotic coma
- •Symptoms of poorly controlled diabetes that would preclude participation in this trial
研究组 & 干预措施
Dapagliflozin + Metformin XR
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks
Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
干预措施: Dapagliflozin (Drug)
Dapagliflozin + Metformin XR
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks
Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
干预措施: Metformin XR (Drug)
Dapagliflozin + Placebo
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks.
Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
干预措施: Dapagliflozin (Drug)
Dapagliflozin + Placebo
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks.
Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
干预措施: metformin HCl Modified Release matching Placebo (Drug)
Metformin XR + Placebo
Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks
Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks
干预措施: Metformin XR (Drug)
Metformin XR + Placebo
Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks
Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks
干预措施: dapagliflozin matching Placebo (Drug)
结局指标
主要结局
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 (Last Observation Carried Forward) - Randomized Treated Participants
时间窗: Week 24
Adjusted mean change in HbA1c from baseline at Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, ie, last observation carried forward (LOCF) was determined. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the Qualification and Lead-In Periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the Double-Blind Period.
次要结局
- Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Adjusted Mean Change From Baseline in HbA1C at Week 24 (LOCF) in Participants Whose Baseline HbA1C Category ≥9.0%(Week 24)
- The Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants(Day 1 of Double Blind Period to end of Week 24 Plus 30 days)
- Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants(Baseline to last dose plus 4 days in 12 Week Double Blind Period)
- Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants(Week 24)
- Mean Change From Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants(Week 24)
- Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants(Baseline to Week 24/end of treatment plus 4 days)
- Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants(Baseline to Week 24/end of treatment plus 30 days)