A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 1,136
- 试验地点
- 1
- 主要终点
- Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue
研究概览
简要总结
A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination with Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects with Type 2 Diabetes who have Inadequate Glycaemic Control
详细描述
Allocation: Randomized Endpoint Classification: Efficacy/Safety study Intervention Model: Parallel Assignment Masking: Double Blind Primary Purpose: Treatment
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with type 2 diabetes mellitus;
- •HbA1c ≥8% but ≤12%; 3.Fasting C-peptide ≥1.0 ng/ml;
- •Subject will be drug naïve;
- •Body mass index ≤40 kg/m2.
排除标准
- •Symptoms of poorly controlled diabetes;
- •Chronic or repeated intermittent corticosteroid treatment ;
- •Calculated creatinine clearance <60 ml/min or serum creatinine >132.6 μmol/L (>1.5 mg/dL) for men, >123.8 μmol/L (>1.4 mg/dL) for women;
- •Creatine Kinase ≥3x ULN; 5.Abnormal TSH value at screening will be further evaluated by free T4, subjects with an abnormal free T4 will be excluded;
- •History of administration of any antihyperglycaemic therapy for a total of 28 days or for more than three consecutive days or a total of seven non-consecutive days during the eight weeks prior to screening;
- •Current treatment with a strong CYP3A4/5 inhibitor;
- •Prior treatment with saxagliptin or any DPP-4 inhibitor;
- •Significant or history of cardiovascular disease, renal disease, psychiatric disorders, Immunocompromised individuals, hemoglobinopathies, liver disease, Pancreatitis.
研究组 & 干预措施
Saxagliptin 5 mg + Metformin (500 mg with titration)
Saxagliptin 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
干预措施: Saxagliptin 5 mg (Drug)
Saxagliptin 5 mg + Metformin (500 mg with titration)
Saxagliptin 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
干预措施: Metformin 500 mg with titration (Drug)
Saxagliptin 5 mg + Placebo
Saxagliptin 5 mg once daily and Placebo 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
干预措施: Saxagliptin 5 mg (Drug)
Saxagliptin 5 mg + Placebo
Saxagliptin 5 mg once daily and Placebo 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
干预措施: Placebo 500 mg for metformin (with titration) (Drug)
Metformin (500 mg with titration) + Placebo
Placebo 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
干预措施: Placebo 5 mg for Saxagliptin (Drug)
Metformin (500 mg with titration) + Placebo
Placebo 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
干预措施: Metformin 500 mg with titration (Drug)
结局指标
主要结局
Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue
时间窗: Baseline to Week 24 (prior to rescue)
To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to reduction in HbA1c (%) at the end of 24 weeks of double-blinded treatment.
次要结局
- Glycemic Response Defined as HbA1c < 7.0% at Week 24(Week 24 (prior to rescue))
- Change From Baseline to Week 24 (Prior to Rescue) in Fasting Plasma Glucose(Baseline to Week 24 prior to rescue)
- Patients Rescued for Failing to Achieve Pre-specified Glycemic Targets or Discontinuation for Lack of Efficacy During the 24-week Double-blind Treatment Phase(Baseline to Week 24)
- Change From Baseline to Week 24 (Prior to Rescue) in Area Under the Curve From 0-180 Minutes for Postprandial Glucose Response to a Meal Tolerance Test(Baseline to Week 24 prior to rescue)
- Glycemic Response Defined as HbA1c ≤ 6.5% at Week 24(Week 24 (prior to rescue))
- Change From Baseline to Week 24 in 120-minute Postprandial Glucose Response to a Meal Tolerance Test(Baseline to Week 24 prior to rescue)