Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin: A 48-week Randomized, Open-label, Multicentre Phase IIIB Study to Compare the Effectiveness of Combination Therapy to Monotherapy in Type 2 Diabetes Mellitus Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 391
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in A1C at Month 6
研究概览
简要总结
The incidence of type 2 diabetes is on the increase. According to recent Canadian Diabetes Association guidelines glucose control, based on the A1C measurement, needs to be achieved within a 6-12 month period of time after the initial diagnosis of type 2 diabetes. The guidelines on the use of antihyperglycemic agents identify the potential benefits of sub-maximal oral combination therapy in order to achieve more rapid and improved glycemic control compared with higher dose monotherapy. Furthermore, many patients on prolonged oral antihyperglycemic monotherapy who then start on combination therapy may not achieve the required target glycemic control. Indeed early initiation of combination therapies may be necessary to achieve and maintain glycemic targets because of the progressive deterioration of pancreatic β cell function and glycemic control.
详细描述
AvandametTM combines two oral antihyperglycemic agents, rosiglitazone maleate and metformin hydrochloride, with different but complementary mechanisms of action to improve glycemic control while reducing circulating insulin levels in patients with type 2 diabetes. AvandiaTM and AmarylTM combine two antidiabetic agents, rosiglitazone maleate and glimepiride. Glimepiride is an effective antihyperglycemic agent which has a low incidence of hypoglycemia, symptomatic hypoglycemia, severe hypoglycemia, and confirmed hypoglycemia. Subjects in this study who are inadequately controlled on diet, exercise and a submaximal dose of metformin or sulfonylurea (SU) will be randomized to either a combination of metformin plus rosiglitazone (AvandametTM) or a combination of AvandiaTM + AmarylTM or a Metformin monotherapy arm. As per the Canadian Diabetes Association (CDA) guidelines, their fasting plasma glucose and A1C to be 7 (mmol/L / percent) or less throughout the study. If the subject does not achieve the target then either AvandametTM or AvandiaTM and AmarylTM or Metformin will be up-titrated in an effort to reach this CDA recommended target. This study will attempt to demonstrate that the either combination arm of rosiglitazone plus metformin (AvandametTM) or the other combination arm of AvandiaTM + AmarylTM will provide greater glycemic control while avoiding the side-effects associated with the use of maximal dose metformin.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes patients
- •18 - 75 years old
- •Type 2 diabetes mellitus (DM) drug naïve or on submaximal oral monotherapy < 3 years
- •A1C criteria at screening:
- •7.1-10% for drug naïve patients after failure of diet control and life-style modification
- •7.1 - 9% on single therapy (e.g. not more 10 mg of Glyburide or 4 mg of Amaryl™ or 1000mg of Metformin) who will start after 2 weeks wash-out. During wash out the following will be done: i) diet and life style modification ii) Angiotensin converting enzyme inhibitor (ACE), aspirin (80 mg), and statin if appropriate
- •Signed informed consent
排除标准
- •Type 1 diabetes
- •Subjects currently treated with insulin
- •Subject treated for previous 3 month with any thiazolidinedione (TZD)
- •Evidence of clinically significant concomitant illnesses which are not controlled by medication and/or may limit participation in the study as judged by the investigator
- •Subjects who have hypersensitivity to any components of study drugs
- •Participation in a clinical trial and/or intake of an investigational drug within 30 days prior to screening.
- •Pregnant or nursing females
- •Females of childbearing potential who are not on adequate birth control
- •Liver enzymes (Alanine Aminotransferase (ALT) > 2.5 times upper limit of normal)
- •Renal impairment: serum creatinine ≥ 136umol/L (males) and ≥ 124 umol/L (females)
- •Congestive Heart Failure (CHF class III/IV)
- •Weight >160 kg
研究组 & 干预措施
Metformin
Metformin 500 mg twice daily titration up to 1000 mg twice daily over 6 months
干预措施: Metformin (Drug)
Avandamet
Avandamet 2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
干预措施: Avandamet (Drug)
Avandia and Amaryl
Avandia + Amaryl 4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
干预措施: Avandia and Amaryl (Drug)
结局指标
主要结局
Mean Change From Baseline in A1C at Month 6
时间窗: Baseline and Month 6
Change from baseline was calculated as the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
次要结局
- Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4(Baseline and Month 4)
- Number of Subjects Achieving A1C Target at Month 12(Month 12)
- Mean Change From Baseline in A1C at Month 4(Baseline and Month 4)
- Number of Subjects Achieving A1C Target at Month 6(Month 6)
- Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12(Baseline and Month 12)
- Number of Subjects Achieving FPG Target at Month 4(Month 4)
- Number of Subjects Achieving A1C Target at Month 4(Month 4)
- Number of Subjects Achieving FPG Target at Month 6(Month 6)
- Mean Change From Baseline in A1C at Month 12(Baseline and Month 12)
- Mean Change From Baseline in C-reactive Protein (CRP) at Month 6(Baseline and Month 6)
- Mean Change From Baseline in C-reactive Protein (CRP) at Month 12(Baseline and Month 12)
- Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6(Baseline and Month 6)
- Number of Subjects Achieving FPG Target at Month 12(Month 12)
- Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6(Baseline and Month 6)
- Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12(Baseline and Month 12)
- Mean Change From Baseline in Adiponectin at Month 6(Baseline and Month 6)
- Mean Change From Baseline in Adiponectin at Month 12(Baseline and Month 12)
研究者
Dr. Anatoly Langer
Chair, Steering Committe
Canadian Heart Research Centre