An Exploratory Phase II/III, Randomized, Double-blind, Placebo Controlled, Parallel Design Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Dapagliflozin and Dapagliflozin in Combination With Saxagliptin in CKD Patients With Type 2 Diabetes Mellitus and Albuminuria Treated With ACEi or ARB
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 459
- 试验地点
- 1
- 主要终点
- Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24
研究概览
简要总结
The purpose of this clinical research study is to determine whether dapagliflozin alone or in combination with saxagliptin can decrease albuminuria and improve glycemic control in patients with Type 2 diabetes, albuminuria and renal impairment (CKD). The study is planned to randomize a total of 450 patients (150 patients per treatment arm)
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
- Double (Participant, 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 prior to any study specific procedures
- •Female or male aged ≥18 years
- •History of type 2 diabetes mellitus for more than 12 months
- •HbA1c≥7.0% and ≤11.0%
- •Stable antidiabetic treatment during the last 12 weeks up to randomization
- •eGFR 25-75 mL/minute/1.73m2, inclusive
- •Micro or macroalbuminuria (UACR 30 - 3500 mg/g)
- •Treatment with ACE inhibitor or an ARB for at least 3 months prior to screening
- •Body mass index between 20 and 45 kg/m2
排除标准
- •Any of the following CV/Vascular Diseases within 3 month prior to signing the consent at Visit 1:
- •Myocardial infarction
- •cardiac surgery or revascularization (CABG/PTCA)
- •unstable angina
- •unstable HF
- •New York Heart Association (NYHA) Class III-IV
- •transient ischemic attack (TIA) or significant cerebrovascular disease
- •unstable or previously undiagnosed arrhythmia
- •Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency
- •Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3X ULN
- •Total Bilirubin (TB) >2 mg/dL (34.2 μmol/L)
- •History of acute kidney injury requiring renal replacement therapy (dialysis or ultrafiltration) or any biopsy or imaging verifying intercurrent kidney disease other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis
- •Ongoing treatment with a SGLT2 inhibitor, GLP-1 agonist or DPP4 inhibitors
- •Any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient or patient suspected or with confirmed poor protocol or medication compliance
研究组 & 干预措施
Dapagliflozin 10mg
Tablets administered orally once daily for 24 weeks
干预措施: Dapagliflozin 10 mg (Drug)
Dapagliflozin 10mg + Saxagliptin 2.5mg
Tablets administered orally once daily for 24 weeks
干预措施: Saxagliptin 2.5 mg (Drug)
Placebo
Tablets administered orally once daily for 24 weeks
干预措施: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg (Drug)
结局指标
主要结局
Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24
时间窗: Baseline and Week 24
UACR was analysed at baseline and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. UACR values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.
Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24
时间窗: Baseline and Week 24
HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a mixed model repeated measures (MMRM) model.
次要结局
- Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24(Baseline and Week 24)
- Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24(Baseline and Week 24)
- Percentage of Patients Achieving at Least 30% Reduction in UACR at Week 24(From baseline up to Week 24)
- Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at Week 24(From baseline to Week 24)
- Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24(Baseline and Week 24)
- Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at Week 24(Baseline and Week 24)