Back to resultsComparing the Efficacy and Safety of Biphasic Insulin Aspart 30 and Biphasic Human Insulin 30 on Blood Sugar Control in Subjects With Type 2 Diabetes
Primary Purpose
Diabetes, Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
biphasic insulin aspart 30
biphasic human insulin 30
metformin
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes
Eligibility Criteria
Inclusion Criteria:
- Type 2 diabetes diagnosed for at least 6 months
- Insulin-naive (less than or equal to 1 week of daily use of insulin therapy)
- Treatment with metformin as monotherapy or in combination therapy with other OAD(s) for at least 3 months prior to this trial
- Currently on metformin greater than or equal to 1000 mg/day for at least 2 weeks
- Currently at least one of other OAD(s) reaching at least one-half of the recommended maximum dose for at least 2 weeks
- Glycosylated haemoglobin (HbA1c) between 7.5-11.0%
- Body Mass Index (BMI) between 18.5 - 35.0 kg/m^2
- Be able and willing to perform continuous glucose monitoring system (CGMS ) and self-monitored blood glucose (SMBG)
Exclusion Criteria:
- Known or suspected allergy to trial product(s) or related products
- Any contraindication of metformin
- Receipt of investigational drug within the last 3 months prior to this trial
- Any history of chronic insulin therapy (more than 1 week of daily use)
- Systemically treated with thiazolidinediones (TZDs) for more than one month within 6 months prior to this trial
- Pregnancy, nursing mother, or unwillingness to use adequate contraception
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
BIAsp 30
BHI 30
Arm Description
BIAsp 30 (biphasic insulin aspart 30) administered subcutaneously (under the skin) twice daily (before breakfast and dinner) + metformin. Initial total daily dose of 0.3 U or IU/kg body weight followed by individual dose adjustment for BIAsp 30 was performed over the first 4 weeks (titration period) to achieve the pre-meal blood glucose target of 4.4-6.1 mmol/l. The achieved dose was maintained for the last 2 weeks of treatment unless hypoglycaemia occurred.
BHI 30 (biphasic human insulin 30) administered subcutaneously (under the skin) twice daily (30 minutes before breakfast and dinner) + metformin. Initial total daily dose of 0.3 U or IU/kg body weight followed by individual dose adjustment for BHI 30 was performed over the first 4 weeks (titration period) to achieve the pre-meal blood glucose target of 4.4-6.1 mmol/l. The achieved dose was maintained for the last 2 weeks of treatment unless hypoglycaemia occurred.
Outcomes
Primary Outcome Measures
Change in IAUC (Incremental Area Under the Curve) for Postprandial Glucose (0-4 Hours) Over 3 Main Meals
The blood glucose profiles were monitored by CGMS (Continuous Glucose Monitoring System) for 72 hours at baseline (week 0) and end of treatment (week 6). IAUC was calculated using the trapezoidal method. The arithmetic mean of IAUC (3 meal-specific incremental areas) of day 1 and day 2 was used as the value of IAUC for each CGMS period
Secondary Outcome Measures
Change in Mean IAUC for Postprandial Glucose (0-4 Hours) After Each Meal (Breakfast, Lunch, Dinner) Assessed by CGMS
The blood glucose profiles were monitored by CGMS for 72 hours at baseline (week 0) and end of treatment (week 6). IAUC (0-4 hours) after each meal at 6 weeks and change in IAUC (0-4 hours) from baseline (week 0) after each meal were to be assessed. The arithmetic mean of day 1 and day 2 for each meal-specific incremental area (breakfast, lunch, dinner) was calculated.
Mean FBG (Fasting Blood Glucose) Assessed by CGMS
The blood glucose profiles were monitored by CGMS for 72 hours at end of treatment (week 6). Mean FBG assessed by CGMS at 6 weeks. FBG was read on the CGMS glucose curves at 06:00 each morning over the 72 hours. The arithmetic mean of day 1 and day 2 was used as the value of mean FBG for each CGMS period.
Change in Mean FBG Assessed by CGMS
The blood glucose profiles were monitored by CGMS for 72 hours at baseline (week 0) and at end of treatment (week 6). Change in mean FBG from baseline (week 0) was assessed. FBG was read on the CGMS glucose curves at 06:00 each morning over the 72 hours. The arithmetic mean of day 1 and day 2 was used as the value of mean FBG for each CGMS period.
Change in FPG (Fasting Plasma Glucose)
FPG was analysed by local laboratories at baseline (week 0) and end of treatment (week 6). Change in FPG at end of treatment (week 6) from baseline (week 0) was to be assessed.
Change in 8-point SMBG (Self-monitored Blood Glucose) Profiles
Subjects were asked to perform 8-point SMBG profiles using the provided blood glucose meter on one day within 72 hours CGMS monitoring period at week 0 and week 6. Change in blood glucose level at end of treatment (week 6) from baseline (week 0) at each time point was to be assessed respectively. Blood glucose levels were measured at the following 8 time points: Before each meal (breakfast, lunch and dinner), 120 minutes after the start of each meal, at bedtime and at 3 am in the morning.
Change in Prandial Blood Glucose Increment
Subjects were asked to perform 8-point SMBG profiles using the provided blood glucose meter on one day within 72 hours CGMS monitoring period at week 0 and week 6 respectively. Prandial increment was the difference between the blood glucose (BG) value measured 120 minutes after meal and the BG value measured before meal.
Change in MAGE (Mean Amplitude of Glycaemic Excursions) Assessed by CGMS
MAGE is a parameter to monitor the intraday blood glucose excursions. It was calculated using CGMS data and as the arithmetic mean of glycaemic excursion with the criterion that both segments (ascending and descending parts) of the glycaemic excursion exceed of the value of one standard deviation of respective 24-hour blood glucose value. The direction of calculation (peak-to-nadir or nadir-to-peak) was established by the direction of the first excursion. The arithmetic mean of the glycaemic excursion of day 1 and day 2 was the value of MAGE for each CGMS
Change in GA (Glycated Albumin)
Glycated Albumin is used as a general glycaemic control parameter. Analysed by laboratory. GA was measured at baseline (week 0) and end of treatment (week 6). Change in GA at end of treatment (week 6) from baseline (week 0) was assessed.
Change in Glycosylated Haemoglobin (HbA1c)
Duration of Hypoglycaemic Events Based on CGMS
The CGMS device recorded blood glucose levels every 10 seconds then stored a smoothed average over 5 minutes. The range of blood glucose detection was 2.2-22 mmol/l. Hypoglycaemia was defined as blood glucose readings below 3.5 mmol/l or below 2.5 mmol/l, respectively. The duration of the hypoglycaemic episodes was quantified by accumulating the total time the CGMS profiles stays below the defined threshold (i.e. below 3.5 mmol/l or below 2.5 mmol/l, respectively).
Hypoglycaemia Based on Self-reported Episodes
Total number of hypoglycaemic episodes occurring in the trial after baseline (week 0) until the end of treatment (week 6). Hypoglycaemic episodes are classified as major, minor or symptoms only: Major if the subject was unable to treat her/himself; minor if subject was able to treat her/himself and self monitored blood glucose (SMBG) was below 2.8 mmol/L; symptoms only if subject was able to treat her/himself and with no blood glucose measurement or SMBG higher than or equal to 2.8 mmol/L.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00807092
Brief Title
Comparing the Efficacy and Safety of Biphasic Insulin Aspart 30 and Biphasic Human Insulin 30 on Blood Sugar Control in Subjects With Type 2 Diabetes
Official Title
Comparison of the Efficacy on Glycaemic Control and Safety Profile of Biphasic Insulin Aspart 30 and Biphasic Human Insulin 30 Both in Combination With Metformin in Insulin-naïve Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Drugs (OADs) Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial is conducted in Asia. The aim of this clinical trial is to investigate the blood sugar lowering effect and the safety profile of biphasic insulin aspart 30 compared to biphasic human insulin 30, both in combination with metformin in Chinese insulin-naive subjects with type 2 diabetes when failing on oral antidiabetic drug (OAD) therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
145 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIAsp 30
Arm Type
Experimental
Arm Description
BIAsp 30 (biphasic insulin aspart 30) administered subcutaneously (under the skin) twice daily (before breakfast and dinner) + metformin. Initial total daily dose of 0.3 U or IU/kg body weight followed by individual dose adjustment for BIAsp 30 was performed over the first 4 weeks (titration period) to achieve the pre-meal blood glucose target of 4.4-6.1 mmol/l. The achieved dose was maintained for the last 2 weeks of treatment unless hypoglycaemia occurred.
Arm Title
BHI 30
Arm Type
Experimental
Arm Description
BHI 30 (biphasic human insulin 30) administered subcutaneously (under the skin) twice daily (30 minutes before breakfast and dinner) + metformin. Initial total daily dose of 0.3 U or IU/kg body weight followed by individual dose adjustment for BHI 30 was performed over the first 4 weeks (titration period) to achieve the pre-meal blood glucose target of 4.4-6.1 mmol/l. The achieved dose was maintained for the last 2 weeks of treatment unless hypoglycaemia occurred.
Intervention Type
Drug
Intervention Name(s)
biphasic insulin aspart 30
Intervention Description
The initial doses for BIAsp 30 twice-daily regimen will be recommended to start at a total daily dose of 0.3 U/kg body weight and to be equally divided (1/2:1/2) between pre-breakfast and pre-dinner
Intervention Type
Drug
Intervention Name(s)
biphasic human insulin 30
Intervention Description
The initial doses for BHI 30 twice-daily regimen will be recommended to start at a total daily dose of 0.3 IU/kg body weight and to be divided in the ratio of 2/3:1/3 between pre-breakfast and pre-dinner
Intervention Type
Drug
Intervention Name(s)
metformin
Intervention Description
Metformin dose must remain the same as that used prior to the trial.
Primary Outcome Measure Information:
Title
Change in IAUC (Incremental Area Under the Curve) for Postprandial Glucose (0-4 Hours) Over 3 Main Meals
Description
The blood glucose profiles were monitored by CGMS (Continuous Glucose Monitoring System) for 72 hours at baseline (week 0) and end of treatment (week 6). IAUC was calculated using the trapezoidal method. The arithmetic mean of IAUC (3 meal-specific incremental areas) of day 1 and day 2 was used as the value of IAUC for each CGMS period
Time Frame
Week 0, week 6
Secondary Outcome Measure Information:
Title
Change in Mean IAUC for Postprandial Glucose (0-4 Hours) After Each Meal (Breakfast, Lunch, Dinner) Assessed by CGMS
Description
The blood glucose profiles were monitored by CGMS for 72 hours at baseline (week 0) and end of treatment (week 6). IAUC (0-4 hours) after each meal at 6 weeks and change in IAUC (0-4 hours) from baseline (week 0) after each meal were to be assessed. The arithmetic mean of day 1 and day 2 for each meal-specific incremental area (breakfast, lunch, dinner) was calculated.
Time Frame
Week 0, Week 6
Title
Mean FBG (Fasting Blood Glucose) Assessed by CGMS
Description
The blood glucose profiles were monitored by CGMS for 72 hours at end of treatment (week 6). Mean FBG assessed by CGMS at 6 weeks. FBG was read on the CGMS glucose curves at 06:00 each morning over the 72 hours. The arithmetic mean of day 1 and day 2 was used as the value of mean FBG for each CGMS period.
Time Frame
Week 6
Title
Change in Mean FBG Assessed by CGMS
Description
The blood glucose profiles were monitored by CGMS for 72 hours at baseline (week 0) and at end of treatment (week 6). Change in mean FBG from baseline (week 0) was assessed. FBG was read on the CGMS glucose curves at 06:00 each morning over the 72 hours. The arithmetic mean of day 1 and day 2 was used as the value of mean FBG for each CGMS period.
Time Frame
Week 0, week 6
Title
Change in FPG (Fasting Plasma Glucose)
Description
FPG was analysed by local laboratories at baseline (week 0) and end of treatment (week 6). Change in FPG at end of treatment (week 6) from baseline (week 0) was to be assessed.
Time Frame
Week 0, Week 6
Title
Change in 8-point SMBG (Self-monitored Blood Glucose) Profiles
Description
Subjects were asked to perform 8-point SMBG profiles using the provided blood glucose meter on one day within 72 hours CGMS monitoring period at week 0 and week 6. Change in blood glucose level at end of treatment (week 6) from baseline (week 0) at each time point was to be assessed respectively. Blood glucose levels were measured at the following 8 time points: Before each meal (breakfast, lunch and dinner), 120 minutes after the start of each meal, at bedtime and at 3 am in the morning.
Time Frame
Week 0, Week 6
Title
Change in Prandial Blood Glucose Increment
Description
Subjects were asked to perform 8-point SMBG profiles using the provided blood glucose meter on one day within 72 hours CGMS monitoring period at week 0 and week 6 respectively. Prandial increment was the difference between the blood glucose (BG) value measured 120 minutes after meal and the BG value measured before meal.
Time Frame
Week 0, Week 6
Title
Change in MAGE (Mean Amplitude of Glycaemic Excursions) Assessed by CGMS
Description
MAGE is a parameter to monitor the intraday blood glucose excursions. It was calculated using CGMS data and as the arithmetic mean of glycaemic excursion with the criterion that both segments (ascending and descending parts) of the glycaemic excursion exceed of the value of one standard deviation of respective 24-hour blood glucose value. The direction of calculation (peak-to-nadir or nadir-to-peak) was established by the direction of the first excursion. The arithmetic mean of the glycaemic excursion of day 1 and day 2 was the value of MAGE for each CGMS
Time Frame
Week 0, Week 6
Title
Change in GA (Glycated Albumin)
Description
Glycated Albumin is used as a general glycaemic control parameter. Analysed by laboratory. GA was measured at baseline (week 0) and end of treatment (week 6). Change in GA at end of treatment (week 6) from baseline (week 0) was assessed.
Time Frame
Week -2, week 6
Title
Change in Glycosylated Haemoglobin (HbA1c)
Time Frame
Week -2, week 6
Title
Duration of Hypoglycaemic Events Based on CGMS
Description
The CGMS device recorded blood glucose levels every 10 seconds then stored a smoothed average over 5 minutes. The range of blood glucose detection was 2.2-22 mmol/l. Hypoglycaemia was defined as blood glucose readings below 3.5 mmol/l or below 2.5 mmol/l, respectively. The duration of the hypoglycaemic episodes was quantified by accumulating the total time the CGMS profiles stays below the defined threshold (i.e. below 3.5 mmol/l or below 2.5 mmol/l, respectively).
Time Frame
72-hour monitoring period at Week 0 and Week 6
Title
Hypoglycaemia Based on Self-reported Episodes
Description
Total number of hypoglycaemic episodes occurring in the trial after baseline (week 0) until the end of treatment (week 6). Hypoglycaemic episodes are classified as major, minor or symptoms only: Major if the subject was unable to treat her/himself; minor if subject was able to treat her/himself and self monitored blood glucose (SMBG) was below 2.8 mmol/L; symptoms only if subject was able to treat her/himself and with no blood glucose measurement or SMBG higher than or equal to 2.8 mmol/L.
Time Frame
Weeks 0-6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 2 diabetes diagnosed for at least 6 months
Insulin-naive (less than or equal to 1 week of daily use of insulin therapy)
Treatment with metformin as monotherapy or in combination therapy with other OAD(s) for at least 3 months prior to this trial
Currently on metformin greater than or equal to 1000 mg/day for at least 2 weeks
Currently at least one of other OAD(s) reaching at least one-half of the recommended maximum dose for at least 2 weeks
Glycosylated haemoglobin (HbA1c) between 7.5-11.0%
Body Mass Index (BMI) between 18.5 - 35.0 kg/m^2
Be able and willing to perform continuous glucose monitoring system (CGMS ) and self-monitored blood glucose (SMBG)
Exclusion Criteria:
Known or suspected allergy to trial product(s) or related products
Any contraindication of metformin
Receipt of investigational drug within the last 3 months prior to this trial
Any history of chronic insulin therapy (more than 1 week of daily use)
Systemically treated with thiazolidinediones (TZDs) for more than one month within 6 months prior to this trial
Pregnancy, nursing mother, or unwillingness to use adequate contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
12. IPD Sharing Statement
Links:
URL
http://novonordisk-trials.com
Description
Clinical Trials at Novo Nordisk
Learn more about this trial
Comparing the Efficacy and Safety of Biphasic Insulin Aspart 30 and Biphasic Human Insulin 30 on Blood Sugar Control in Subjects With Type 2 Diabetes
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