NCT03344341终止4 期
A 24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy and Safety of Dapagliflozin as Monotherapy Compared With Acarbose in Drug-Naive Patients With Type 2 Diabetes Mellitus (T2DM) in China
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 304
- 试验地点
- 1
- 主要终点
- Absolute change from baseline in HbA1c at Week 24
研究概览
简要总结
This is a 24-week, multicenter, randomized, open-label, parallel-group, active controlled Phase IV study to assess the efficacy and safety of Dapagliflozin as monotherapy compared with Acarbose in patients with T2DM who were inadequately controlled with diet and exercise.
The study is designed to evaluate the efficacy and safety of dapagliflozin monotherapy compared with acarbose monotherapy in patients with T2DM inadequately controlled with diet and exercise.
详细描述
- Study design This is a 24-week, multicenter, randomized, open-label, parallel-group, active controlled Phase IV study The open-label study design rather than double-blind is considered due to the difficulty of placebo supply. The primary efficacy endpoint will be blinded to both patients and investigators, so the measurements as well as the management of the patients will not be impacted by the design of open-label.
The study is powered to show non-inferiority of dapagliflozin versus acarbose regarding with HbA1c reduction.
A non-inferiority margin of 0.25% for the difference of the reduction in HbA1c is considered in the study.
- Primary and secondary outcome variables In the clinical guidelines for type 2 diabetes, HbA1c is recommended as gold standard for determination of glycemic control and is therefore chosen as the primary outcome variable. Certain secondary outcome variables have been selected for additional assessment because of their clinical relevance and importance.
- Dosing and study duration Dapagliflozin will be started from 5 mg once a day, taken orally in the morning, before or after food. In patients tolerating dapagliflozin 5 mg once a day, the dose will be increased to 10 mg once a day from the second week.
Acarbose will be started from 50 mg once a day at dinner during the first week and titrated up to 50 mg twice a day at lunch and dinner in the second week, 50 mg three times a day at three meals in the third week, and 100 mg three times a day from the fourth week onwards.
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
- None
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
- •Diagnosed within the past 12 months with T2DM according to 1999 World Health Organization(WHO) criteria.
- •Men and women aged at least 18 years at screening.
- •Either not received oral anti-diabetic drugs or had been on short-term (1 month) treatment that had been discontinued 3 months before enrolment.
- •HbA1c ≥ 7.5% and ≤ 10.5% at screening and HbA1c ≥ 7.0% and ≤ 10.5% at pre-randomization visit.
- •FPG ≤ 13.3 mmol/L (≤ 240 mg/dL) .
- •BMI≥18.5 kg/m2 and ≤ 45.0 kg/m2 .
- •C-peptide ≥0.33nmol/L(≥1.0 ng/mL).
- •Able and willing to provide written informed consent and to comply with the study.
排除标准
- •Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.
- •Diagnosis or history of:
- •a. Acute metabolic diabetic complications such as ketoacidosis or hyperglycemic hyperosmolar state b. Diabetes insipidus.
- •Requirement for insulin therapy. Symptoms of poorly controlled diabetes, including but not limited to, marked polyuria and polydipsia with >10% weight loss during the 3 months before enrollment.
- •Triglycerides (fasting) > 9.3 mmol/L (> 800 mg/dL).
- •Patients with clinically apparent hepatobiliary disease, including but not limited to chronic active hepatitis and/or severe hepatic insufficiency. Alanine Aminotransferase(ALT) or Aspartate Aminotransferase(AST) > 3x upper limit of normal (ULN), or serum total bilirubin (TB) >34.2 μmol/L (>2 mg/dL).
- •Patients with following renal disease history or renal disease related features:
- •History of unstable or rapidly progressing renal disease;
- •Patients with moderate /severe renal impairment or end-stage renal disease (eGFR< 60 mL/min/1.73 m2);
- •Urinary albumin: creatinine ratio >1800 mg/g;
- •Serum creatinine (Cr) ≥133 μmol/L (≥1.50 mg/dL) for male subjects; Serum Cr≥124 μmol/L (≥1.40 mg/dL) for female subjects;
- •Conditions of congenital renal glycosuria.
- •Severe uncontrolled hypertension defined as SBP ≥180 mmHg and/or BP ≥110 mmHg; Patients with SBP < 95mmHg.
- •Any of the following cardiovascular diseases within 6 months of the enrollment visit:
- •Myocardial infarction;
- •Cardiac surgery or revascularization (coronary artery bypass graft/percutaneous transluminal coronary angioplasty);
- •Unstable angina;
- •Congestive heart failure New York Heart Association Class III or IV;
- •Transient ischemic attack or significant cerebrovascular disease.
- •History of gastrointestinal disease or surgery including Roemheld Syndrome, severe hernia, intestinal obstruction, intestinal ulcer, gastroenterostomy, enterectomy, bariatric surgery or lap-band procedure.
- •Malignancy within 5 years of the enrollment visit (with the exception of treated basal cell or treated squamous cell carcinoma).
- •Known immunocompromised status, including but not limited to, individuals who had undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).
- •Any subject who, in the judgment of the investigator, was at risk for dehydration or volume depletion that might affect the interpretation of efficacy or safety data.
- •History of bone fracture secondary to diagnosed severe osteoporosis.
- •Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases as judged by the Investigator.
- •Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months before enrollment visit.
- •Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, or phendimetrazine within 30 days of enrollment visit.
- •Any subject who was currently abusing alcohol or other drugs or had done so within the last 6 months.
- •Donation of blood or blood products, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks before the enrollment visit.
- •History of hypersensitivity reaction to dapagliflozin or acarbose. Allergies or contraindication to the contents of dapagliflozin tablets or acarbose tablets.
- •Previous participation in a clinical trial with dapagliflozin.
- •Administration of any other investigational drug within 30 days of planned enrollment to this study, or within 5 half-life periods of other investigational drugs.
- •Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data.
研究组 & 干预措施
Dapagliflozin
Experimental
Dapagliflozin is started from 5 mg once a day, taken orally in the morning, before or after breakfast. From the third week, the dose will be increased to 10 mg once a day and last to the end of the study.
干预措施: Dapagliflozin (Drug)
Acarbose
Active Comparator
Acarbose is started from 50 mg once a day at dinner during the first week, titrated up to 50 mg twice a day at lunch and dinner in the second week, 50 mg three times a day at three meals in the third week, and 100 mg three times a day till the end of the study.
干预措施: Acarbose (Drug)
结局指标
主要结局
Absolute change from baseline in HbA1c at Week 24
时间窗: At week 24
Which will be derived using the HbA1c (%) at week 24 minus HbA1c (%) at baseline.
次要结局
- Absolute change from baseline in 2h postprandial glucose (PPG)(From baseline to week 24)
- Absolute change from baseline in systolic blood pressure (SBP)(From baseline to week 24)
- Percentage of patients with reduction of SBP ≥3 mmHg(From baseline to week 24)
- Percentage of patients achieving HbA1c<7.0%(From baseline to week 24)
- Percentage of patients with reduction of HbA1c≥0.5%(From baseline to week 24)
- Percentage of patients at Week 24 with reduction of HbA1c≥0.5%, body weight≥3% and SBP ≥3mmHg from baseline(From baseline to week 24)
- Absolute change from baseline in fasting plasma glucose (FPG)(From baseline to week 24)
- Absolute change from baseline in body weight(From baseline to week 24)
- Percentage of patients with reduction of body weight ≥3%(From baseline to week 24)
研究者
研究点 (1)
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