A Multi-Center, Randomized, Double-Blind, Active-Controlled , Parallel Group, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin 5mg Co-administered With Dapagliflozin 5mg Compared to Saxagliptin 5mg or Dapagliflozin 5mg All Given as Add-on Therapy to Metformin inPatients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Alone
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 905
- 试验地点
- 1
- 主要终点
- Change From Baseline in HbA1c at Week 24
研究概览
简要总结
The aim of this study is to evaluate safety and efficacy of therapy with saxagliptin 5mg co-administered with dapagliflozin 5mg, compared to therapy with saxagliptin 5mg or dapagliflozin 5mg in patients who are inadequately controlled on ≥1500mg/day of metformin monotherapy.
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
- •Patients aged ≥18 years old at time of informed consent;
- •Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C≥7.5% to ≤10.0% at screening visit;
- •Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg per day;
- •BMI ≤45.0kg/m2 at Enrolment visit;
- •Fasting Plasma Glucose (FPG) ≤ 270mg/dl(15.0mmol/L) at the enrolment visit;
- •For Females Only: Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of study medication in such a manner that the risk of pregnancy is minimized.
排除标准
- •History of diabetes insipidus, Type 1 diabetes or Latent Autoimmune Diabetes of Adults, diabetic ketoacidosis or hyperosmolar nonketotic coma and Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to Enrolment (Visit 1), or other signs and symptoms.
- •History of pancreatitis.
- •Administration of any antihyperglycaemic therapy, other than metformin, for more than 14 days (consecutive or not) during the 8 weeks prior to enrolment
- •Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment.
- •Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency and/or significant abnormal liver function, including patients with Alanine transaminase (ALT) and/or Aspartate transaminase (AST) ≥3x ULN (Upper Limit of Normal)and/or Total Bilirubin ≥2.0x ULN. History of severe hepatobiliary disease or hepatotoxicity with any medication. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for Hepatitis viral antibody ImmunoglobulinM (IgM), Hepatitis B surface antigen, and Hepatitis C virus antibody.
- •Moderate or severe impairment of renal function [defined as Estimated Glomerular Filtration Rate (eGFR) <60milliLitre/min/1.73 m2 (estimated by Modification in Diet and Renal Disease (MDRD)) or serum creatinine ≥1.5mg/dL in males or ≥1.4mg/dL in females]. Conditions of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.
- •History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study.
研究组 & 干预措施
Saxagliptin+Dapagliflozin+Metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin
干预措施: Dapagliflozin (Drug)
Saxagliptin+Dapagliflozin+Metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin
干预措施: Saxagliptin (Drug)
Dapagliflozin+Saxagliptin placebo+Metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Dapagliflozin and Saxagliptin Placebo
干预措施: Dapagliflozin (Drug)
Dapagliflozin+Saxagliptin placebo+Metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Dapagliflozin and Saxagliptin Placebo
干预措施: Placebo for Saxagliptin (Drug)
Saxagliptin+Dapagliflozin placebo+metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin placebo
干预措施: Placebo for Dapagliflozin (Drug)
Saxagliptin+Dapagliflozin placebo+metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin placebo
干预措施: Saxagliptin (Drug)
结局指标
主要结局
Change From Baseline in HbA1c at Week 24
时间窗: Baseline and week 24
To demonstrate the superiority of the change from baseline HbA1c achieved with the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually after 24 weeks. Results were presented for the modified full analysis set. Note: Baseline was defined as the last assessment on or prior to the date of the first dose of the study medication.
次要结局
- Proportion of Participants Achieving HbA1c <7.0% at 24 Weeks(Baseline and week 24)
- Change in Fasting Plasma Glucose at 24 Weeks(Baseline and week 24)
- Change in Total Body Weight at 24 Weeks(Baseline and week 24)