A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Asian Subjects With T2DM and Inadequate Glycemic Control on Metformin and Saxagliptin (DS Navigation)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Mean change from baseline in HbA1c at Week 24
研究概览
简要总结
This is a 24-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group, phase 3 study designed to evaluate if the safety and efficacy of dapagliflozin 5 mg or 10 mg added to saxagliptin 5 mg plus metformin is superior to placebo added to saxagliptin 5 mg plus metformin in reducing hemoglobin A1c (HbA1c).
详细描述
This study will be conducted in approximately 36 sites in Asian countries. Approximately 1004 subjects will be screened and 342 randomized. Prior to the screening, subjects of Stratum A should have a stable dose of metformin (≥1500 mg/day or a maximal tolerated dose) for at least 8 weeks. And subjects of Stratum B should have a stable dose of metformin (≥1500 mg/day or a maximal tolerated dose) AND a dipeptidyl peptidase-4 inhibitor at maximum approved dose for at least 8 weeks prior to the screening. Eligible subjects who complete the screening visit will enter the lead-in period, which includes open-label saxagliptin 5 mg and metformin treatment for 16 weeks in Stratum A or 8 weeks in Stratum B. At randomization visit, eligible subjects will be randomized into 1 of 3 treatment groups in a 1:1:1 ratio, receiving blinded dapagliflozin 5 mg, 10 mg or placebo plus metformin and saxagliptin 5 mg treatment for 24 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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent before participating in the study
- •Diagnosed with type 2 diabetes mellitus
- •Inadequate glycemic control defined as below:
- •HbA1c ≥ 8.0% and ≤ 11.5% for Stratum A and HbA1c ≥ 7.5% and ≤ 10.5% for Stratum B at screening visit
- •HbA1c ≥ 7.0 and ≤ 10.5% for both strata at Week -2 visit
- •Body mass index ≤ 40.0 kg/m^2
排除标准
- •Women of childbearing potential unable or unwilling to use acceptable birth control, or women who are pregnant or breastfeeding
- •History of diabetes insipidus and type 1 diabetes
- •History of diabetic ketoacidosis requiring medical intervention within 1 month prior to screening
- •Subjects with moderate to severe renal impairment (defined as estimate glomerular filtration rate calculated by the MDRD Formula < 60mL/min/1.73 m^2 or serum creatinine ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females) or end-stage renal disease
- •History of unstable or rapidly progressing renal disease
- •Subjects with significant hepatic disease or severe hepatic impairment, or positive serologic evidence of current infectious liver disease
- •Prohibited Treatment and Therapies
- •Administration of any anti-hyperglycemic therapy [other than metformin, or Dipeptidyl peptidase-4 (DPP-4) inhibitors] for more than 14 days (consecutive or not) during the 8 weeks prior to screening
- •Any use of Sodium glucose cotransporter 2 (SGLT2) inhibitor within 8 weeks prior to screening
- •Prescription and over-the-counter weight loss medications within 3 months prior to screening
- •Current treatment with potent cytochrome P450 3A4/5 inhibitors
- •Malignancy within 5 years of the screening
- •History of hemoglobinopathy
- •Hematuria (by microscopy) positive at screening visit
- •FPG > 270 mg/dL obtained at open-label period
- •An abnormal TSH value at screening will be further evaluated for free T
- •Subjects with abnormal free T4 values will be excluded
研究组 & 干预措施
Dapagliflozin 10 mg
Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Dapagliflozin 10 mg (Drug)
Dapagliflozin 10 mg
Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Dapagliflozin 5 mg placebo to match (Drug)
Dapagliflozin 10 mg
Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Saxagliptin 5 mg (Drug)
Dapagliflozin 10 mg
Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Metformin (Drug)
Dapagliflozin 5 mg
Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Dapagliflozin 5 mg (Drug)
Dapagliflozin 5 mg
Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Dapagliflozin 10 mg placebo to match (Drug)
Placebo
Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Saxagliptin 5 mg (Drug)
Dapagliflozin 5 mg
Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Saxagliptin 5 mg (Drug)
Dapagliflozin 5 mg
Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Metformin (Drug)
Placebo
Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Dapagliflozin 10 mg placebo to match (Drug)
Placebo
Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Dapagliflozin 5 mg placebo to match (Drug)
Placebo
Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
干预措施: Metformin (Drug)
结局指标
主要结局
Mean change from baseline in HbA1c at Week 24
时间窗: Baseline to Week 24
To compare the mean change from baseline in HbA1c achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment
次要结局
- Mean change from baseline in fasting plasma glucose (FPG) at Week 24(Baseline to Week 24)
- Percent of subjects achieving a therapeutic glycaemic response of HbA1c <7.0% at Week 24(At week 24)
- Mean change in 2-hour postprandial glucose during a meal tolerance test (2-hour MTT) at Week 24(Baseline to Week 24)
- Mean change from baseline in total body weight at Week 24(Baseline to Week 24)