Effect of 50-week Treatment With Stepwise Insulin Intensification of Basal-bolus Insulin Analogues (Insulin Detemir and Aspart) or Biphasic Insulin Aspart 30 (NovoMix 30) All in Combination With Fixed Dose of Metformin on Glycaemic Control (Measured as HbA1c) in Subjects With Type 2 Diabetes. Open Labelled, Randomized, Two-arm, Parallel Group, Multi-centre, Multi-national Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 403
- 试验地点
- 1
- 主要终点
- Glycosylated Haemoglobin (HbA1c)
研究概览
简要总结
This trial is conducted in Africa. The aim of this clinical trial is to investigate the effect of 50 weeks of treatment with different intensified insulin administrations (all in combination with a fixed dose of metformin) on blood sugar control in subjects with type 2 diabetes inadequately controlled by oral anti-diabetic drugs (OADs).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject)
- •Diagnosed type 2 diabetes (WHO 1999 criteria)
- •Currently treated with suboptimal daily dose of OADs (mono or combination therapy) for at least 6 months
- •Male or female age at least 18 years old
- •HbA1c at least 7.0 % and maximum 11.0% for subjects treated with metformin mono-therapy, or maximum 10% for subjects treated with OAD combination therapy
- •BMI maximum 40 kg/m^2
- •Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary
- •Able and willing to be treated with up to 4 insulin injections per day
排除标准
- •Known or suspected allergy to trial product(s) or related products
- •Previous participation in this trial. Participation is defined as randomisation
- •Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)
- •Participated in another clinical trial and received an investigational drug within the last weeks prior to the present trial
- •Impaired hepatic function defined as alanine aminotransferase (ALT) or alkaline phosphatase (ALP) at least 2.5 times upper referenced limit
- •Impaired renal function defined as serum-creatinine at least 1.3 mg/dL (at least 115 mmol/L) for males and at least 1.2 mg/dL (at least 106 mmol/L) for females
- •Subject has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association class III and IV)
- •Severe uncontrolled treated or untreated hypertension (sitting systolic blood pressure at least 180 mmHg or sitting diastolic blood pressure at least 100 mmHg)
- •Proliferative retinopathy or macular oedema requiring acute treatment
- •Metformin contraindications according to the package insert
- •Current treatment with systemic corticosteroids
- •Subject has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject
- •Current addiction to alcohol or other addictive substances as determined by the Investigator
- •Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation in the study or use of the glucose monitor
- •History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator
研究组 & 干预措施
Detemir + Met
Individually adjusted insulin detemir (Detemir) was given subcutaneoulsy (s.c.) at bedtime in the thigh at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, individually adjusted insulin aspart was added to the insulin detemir treatment (up to three doses daily for maximum 36 weeks, injected s.c. [under the skin]) if treatment target of HbA1c below 7.0% was not reached.
干预措施: insulin detemir (Drug)
Detemir + Met
Individually adjusted insulin detemir (Detemir) was given subcutaneoulsy (s.c.) at bedtime in the thigh at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, individually adjusted insulin aspart was added to the insulin detemir treatment (up to three doses daily for maximum 36 weeks, injected s.c. [under the skin]) if treatment target of HbA1c below 7.0% was not reached.
干预措施: insulin aspart (Drug)
Detemir + Met
Individually adjusted insulin detemir (Detemir) was given subcutaneoulsy (s.c.) at bedtime in the thigh at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, individually adjusted insulin aspart was added to the insulin detemir treatment (up to three doses daily for maximum 36 weeks, injected s.c. [under the skin]) if treatment target of HbA1c below 7.0% was not reached.
干预措施: metformin (Drug)
BIAsp 30 + Met
Individually adjusted biphasic insulin aspart 30 (BIAsp 30) was given subcutaneously (s.c.) in the abdomen at dinner at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, the dose was intensified up to 3 doses daily, injected s.c. (under the skin) if treatment target of HbA1c below 7.0% was not reached.
干预措施: biphasic insulin aspart 30 (Drug)
BIAsp 30 + Met
Individually adjusted biphasic insulin aspart 30 (BIAsp 30) was given subcutaneously (s.c.) in the abdomen at dinner at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, the dose was intensified up to 3 doses daily, injected s.c. (under the skin) if treatment target of HbA1c below 7.0% was not reached.
干预措施: metformin (Drug)
结局指标
主要结局
Glycosylated Haemoglobin (HbA1c)
时间窗: Week 50
Estimated mean difference in HbA1c after 50 weeks of treatment
次要结局
- Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment(Week 0, Week 14)
- Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment(Week 26)
- Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment(Week 50)
- Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment(Week 50)
- Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment(Week 14)
- Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment(Week 0, Week 26)
- Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment(Week 0, Week 38)
- Change in Glycosylated Haemoglobin (HbA1c) at Week 50(Week 0, Week 50)
- Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment(Week 38)
- Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment(Week 26)
- Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment(Week 26)
- Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment(Week 38)
- Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment(Week 14)
- Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment(Week 38)
- Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment(Week 50)
- Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment(Week 14)