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Trial record 67 of 1007 for:    Area Under Curve AND insulin

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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ClinicalTrials.gov Identifier: NCT00807092
Recruitment Status : Completed
First Posted : December 11, 2008
Results First Posted : April 11, 2011
Last Update Posted : March 4, 2015
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: biphasic insulin aspart 30
Drug: biphasic human insulin 30
Drug: metformin
Enrollment 145
Recruitment Details A total of 10 sites across China
Pre-assignment Details All eligible subjects had their baseline blood glucose profiles monitored by continuous glucose monitoring system (CGMS) for 72 hours. Following CGMS uninstall and discontinuation of all previous oral anti-diabetic drug (OAD) treatment, subjects were randomised to one of two treatment groups.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Period Title: Overall Study
Started 72 73
Exposed to Drug 71 [1] 73
Completed 71 69
Not Completed 1 4
Reason Not Completed
Adverse Event             0             1
Protocol Violation             0             2
Withdrawal by Subject             1             0
CGMS data collection failed             0             1
[1]
Subject was randomised, but not exposed to any trial drug
Arm/Group Title BIAsp 30 BHI 30 Total
Hide Arm/Group 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. Total of all reporting groups
Overall Number of Baseline Participants 71 73 144
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 73 participants 144 participants
56.5  (9) 54.4  (10.4) 55.5  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 73 participants 144 participants
Female
33
  46.5%
39
  53.4%
72
  50.0%
Male
38
  53.5%
34
  46.6%
72
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 73 participants 144 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
71
 100.0%
73
 100.0%
144
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 71 participants 73 participants 144 participants
66.28  (12) 65.49  (11.4) 65.88  (11.7)
Height at screening  
Mean (Standard Deviation)
Unit of measure:  m
Number Analyzed 71 participants 73 participants 144 participants
1.634  (0.09) 1.623  (0.09) 1.628  (0.09)
BMI (Body Mass Index)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 71 participants 73 participants 144 participants
24.68  (3) 24.74  (3) 24.71  (3)
Duration of diagnosed diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 73 participants 144 participants
7.74  (5.5) 7  (5.2) 7.36  (5.3)
HbA1c at screening  
Mean (Standard Deviation)
Unit of measure:  Percentage of total haemoglobin
Number Analyzed 71 participants 73 participants 144 participants
9.19  (1.05) 9.08  (1.08) 9.13  (1.06)
Metformin monotherapy or combination therapy at randomisation   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 71 participants 73 participants 144 participants
Metformin Monotherapy 20 18 38
Metformin Combination Therapy 51 55 106
[1]
Measure Description: OAD treatment at randomisation
1.Primary Outcome
Title Change in IAUC (Incremental Area Under the Curve) for Postprandial Glucose (0-4 Hours) Over 3 Main Meals
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 67 63
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-1.99  (0.49) -1.977  (0.517)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Change in mean IAUC(0-4hours) of BIAsp 30 after 6 weeks of treatment–Change in mean IAUC(0-4hours) of BHI 30 after 6 weeks of treatment greater than or equal to 0 mol*h/L against the alternative hypothesis(H1): H1: Change in mean IAUC (0-4hours) of BIAsp 30 after 6 weeks of treatment–Change in mean IAUC(0-4hours) of BHI 30 after 6 weeks of treatment less than 0 mol*h/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments A statistical significant threshold p less than 0.025
Method ANCOVA
Comments Treatment and strata as factors; baseline (visit 2) value of mean IAUC(0-4hours) as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.013
Confidence Interval 95%
-1.332 to 1.306
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.666
Estimation Comments BIAsp 30 – BHI 30
2.Secondary Outcome
Title Change in Mean IAUC for Postprandial Glucose (0-4 Hours) After Each Meal (Breakfast, Lunch, Dinner) Assessed by CGMS
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 71 73
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Breakfast, N=68, 64 -3.094  (0.725) -4.272  (0.765)
Lunch, N=69, 66 1.651  (0.897) 1.969  (0.93)
Dinner, N=69, 65 -4.775  (0.539) -4.026  (0.566)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

Null hypothesis and alternative hypothesis for breakfast:

The null hypothesis (H0) was:

H0: Change in mean IAUC(0-4h) of BIAsp 30 for breakfast after 6 weeks of treatment–Change in mean IAUC(0-4h) of BHI 30 for breakfast after 6 weeks of treatment =0 mol*h/L against the alternative hypothesis(H1): H1: Change in mean IAUC (0-4h) of BIAsp 30 for breakfast after 6 weeks of treatment–Change in mean IAUC(0-4h) of BHI 30 for breakfast after 6 weeks of treatment≠0 mol*h/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2412
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; corresponding baseline (week 0) value of mean IAUC(0-4h) as covariate (breakfast/lunch/dinner)
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.178
Confidence Interval 95%
-0.802 to 3.157
Parameter Dispersion
Type: Standard Error of the mean
Value: 1
Estimation Comments Breakfast
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

Null hypothesis and alternative hypothesis for lunch:

The null hypothesis (H0) was:

H0: Change in mean IAUC(0-4h) of BIAsp 30 for lunch after 6 weeks of treatment–Change in mean IAUC(0-4h) of BHI 30 for lunch after 6 weeks of treatment =0 mol*h/L against the alternative hypothesis(H1): H1: Change in mean IAUC (0-4h) of BIAsp 30 for lunch after 6 weeks of treatment–Change in mean IAUC(0-4h) of BHI 30 for lunch after 6 weeks of treatment≠0 mol*h/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.794
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; corresponding baseline (week 0) value of mean IAUC(0-4h) as covariate (breakfast/lunch/dinner)
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.318
Confidence Interval 95%
-2.724 to 2.087
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.216
Estimation Comments Lunch
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

Null hypothesis and alternative hypothesis for dinner:

The null hypothesis (H0) was:

H0: Change in mean IAUC(0-4h) of BIAsp 30 for dinner after 6 weeks of treatment–Change in mean IAUC(0-4h) of BHI 30 for dinner after 6 weeks of treatment =0 mol*h/L against the alternative hypothesis(H1): H1: Change in mean IAUC (0-4h) of BIAsp 30 for dinner after 6 weeks of treatment–Change in mean IAUC(0-4h) of BHI 30 for dinner after 6 weeks of treatment≠0 mol*h/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3093
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; corresponding baseline (week 0) value of mean IAUC(0-4h) as covariate (breakfast/lunch/dinner)
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.749
Confidence Interval 95%
-2.2 to 0.703
Estimation Comments Dinner
3.Secondary Outcome
Title Mean FBG (Fasting Blood Glucose) Assessed by CGMS
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 69 66
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
6.861  (0.193) 6.414  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Change in mean FBG of BIAsp 30 after 6 weeks of treatment–Change in mean FBG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in mean FBG of BIAsp 30 after 6 weeks of treatment–Change in mean FBG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0891
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of mean FBG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.448
Confidence Interval 95%
-0.069 to 0.964
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.261
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Mean FBG Assessed by CGMS
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 69 66
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-2.114  (0.193) -2.561  (0.2)
5.Secondary Outcome
Title Change in FPG (Fasting Plasma Glucose)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) (if a measurement on the withdrawal visit was available) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 70 68
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-2.961  (0.185) -3.456  (0.188)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Change in FPG of BIAsp 30 after 6 weeks of treatment–Change in FPG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in FPG of BIAsp 30 after 6 weeks of treatment–Change in FPG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0472
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of mean FBG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.495
Confidence Interval 95%
0.0060 to 0.984
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.247
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in 8-point SMBG (Self-monitored Blood Glucose) Profiles
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 71 73
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Before Breakfast, N=71, 68 -2.27  (0.2) -2.38  (0.2)
2 hours after Breakfast, N=69, 69 -3.99  (0.41) -5.22  (0.41)
Before Lunch, N=71, 68 -3.46  (0.3) -3.73  (0.31)
2 hours after Lunch, N=70, 69 -2.24  (0.38) -2.41  (0.39)
Before dinner, N=70, 69 -2.59  (0.36) -2.32  (0.37)
2 hours after Dinner, N=70, 69 -4.57  (0.36) -4.1  (0.36)
Bedtime, N=71, 68 -3.84  (0.3) -4.03  (0.31)
3AM, N=68, 66 -2.62  (0.21) -3.39  (0.22)
Average, N=71, 69 -3.16  (0.18) -3.43  (0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.676
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 2) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.11
Confidence Interval 95%
-0.41 to 0.63
Estimation Comments Before breakfast
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.23
Confidence Interval 95%
0.15 to 2.31
Estimation Comments 2 hours after breakfast
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.27
Confidence Interval 95%
-0.53 to 1.08
Estimation Comments Before lunch
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.747
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.17
Confidence Interval 95%
-0.86 to 1.19
Estimation Comments 2 hours after lunch
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.581
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.27
Confidence Interval 95%
-1.23 to 0.69
Estimation Comments Before dinner
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.326
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.47
Confidence Interval 95%
-1.42 to 0.48
Estimation Comments 2 hours after dinner
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.643
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.19
Confidence Interval 95%
-0.61 to 0.99
Estimation Comments Bedtime
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0080
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.77
Confidence Interval 95%
0.21 to 1.33
Estimation Comments 3 AM
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of SMBG :The null hypothesis (H0) was:

H0: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in BG of BIAsp 30 after 6 weeks of treatment–Change in BG of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.274
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of BG as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.27
Confidence Interval 95%
-0.22 to 0.75
Estimation Comments Average
7.Secondary Outcome
Title Change in Prandial Blood Glucose Increment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 71 73
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Breakfast, N=69, 68 -1.82  (0.39) -2.82  (0.4)
Lunch, N=70, 68 1.32  (0.44) 1.27  (0.45)
Dinner, N=69, 69 -1.91  (0.42) -1.85  (0.42)
Average, N=70, 68 -0.81  (0.21) -1.1  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of Prandial Blood Glucose Increment :The null hypothesis (H0) was:

H0: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.062
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of prandial BG increment as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.99
Confidence Interval 95%
-0.05 to 2.04
Estimation Comments Breakfast
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of Prandial Blood Glucose Increment :The null hypothesis (H0) was:

H0: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.933
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of prandial BG increment as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.05
Confidence Interval 95%
-1.12 to 1.22
Estimation Comments Lunch
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of Prandial Blood Glucose Increment :The null hypothesis (H0) was:

H0: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.922
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of prandial BG increment as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.05
Confidence Interval 95%
-1.16 to 1.05
Estimation Comments Dinner
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

For each endpoint of Prandial Blood Glucose Increment :The null hypothesis (H0) was:

H0: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment =0 mmol/L against the alternative hypothesis(H1): H1: Change in prandial BG increment of BIAsp 30 after 6 weeks of treatment–Change in prandial BG increment of BHI 30 after 6 weeks of treatment≠0 mmol/L

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.313
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of prandial BG increment as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.29
Confidence Interval 95%
-0.28 to 0.85
Estimation Comments Average
8.Secondary Outcome
Title Change in MAGE (Mean Amplitude of Glycaemic Excursions) Assessed by CGMS
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 69 69
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.499  (0.273) -0.686  (0.284)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments The full analysis set using LOCF (Last Observation Carried Forward) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6149
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (visit 2) value of mean MAGE as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.187
Confidence Interval 95%
-0.547 to 0.921
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.371
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change in GA (Glycated Albumin)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) (if a measurement on the withdrawal visit was available) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 70 68
Least Squares Mean (Standard Error)
Unit of Measure: percentage point change
-6.147  (0.428) -6.474  (0.438)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Change in GA of BIAsp 30 after 6 weeks of treatment–Change in GA of BHI 30 after 6 weeks of treatment =0 % against the alternative hypothesis(H1): H1: Change in GA of BIAsp 30 after 6 weeks of treatment–Change in GA of BHI 30 after 6 weeks of treatment≠0 %

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5706
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of GA as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.328
Confidence Interval 95%
-0.813 to 1.468
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.577
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in Glycosylated Haemoglobin (HbA1c)
Hide Description [Not Specified]
Time Frame Week -2, week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set using LOCF (Last Observation Carried Forward) (if a measurement on the withdrawal visit was available) consists of all randomised subjects who had been exposed to at least one dose of the trial products.
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 71 68
Least Squares Mean (Standard Error)
Unit of Measure: percentage point change
-1.647  (0.083) -1.667  (0.086)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Change in HbA1c of BIAsp 30 after 6 weeks of treatment–Change in HbA1c of BHI 30 after 6 weeks of treatment =0 % against the alternative hypothesis(H1): H1: Change in HbA1c of BIAsp 30 after 6 weeks of treatment–Change in HbA1c of BHI 30 after 6 weeks of treatment≠0%

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8598
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of HbA1c as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.02
Confidence Interval 95%
-0.243 to 0.243
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.113
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Duration of Hypoglycaemic Events Based on CGMS
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consists of all randomised subjects who were exposed to at least one dose of trial product(s).
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 71 73
Least Squares Mean (Standard Error)
Unit of Measure: Hours
Blood glucose < 3.5 mmol/L, N=70, 68 0.304  (0.094) 0.358  (0.097)
Blood glucose < 2.5 mmol/L, N=70, 68 0.048  (0.028) 0.06  (0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Duration of Hypoglycaemic Events Based on CGMS of BIAsp 30 after 6 weeks of treatment–Duration of Hypoglycaemic Events Based on CGMS of BHI 30 after 6 weeks of treatment =0 hours against the alternative hypothesis(H1): H1: Duration of Hypoglycaemic Events Based on CGMS of BIAsp 30 after 6 weeks of treatment–Duration of Hypoglycaemic Events Based on CGMS of BHI 30 after 6 weeks of treatment≠0 hours

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.671
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of duration of hypoglycaemic events as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.054
Confidence Interval 95%
-0.307 to 0.198
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.128
Estimation Comments Blood glucose below 3.5 mmol/l
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BIAsp 30, BHI 30
Comments

The null hypothesis (H0) was:

H0: Duration of Hypoglycaemic Events Based on CGMS of BIAsp 30 after 6 weeks of treatment–Duration of Hypoglycaemic Events Based on CGMS of BHI 30 after 6 weeks of treatment =0 hours against the alternative hypothesis(H1): H1: Duration of Hypoglycaemic Events Based on CGMS of BIAsp 30 after 6 weeks of treatment–Duration of Hypoglycaemic Events Based on CGMS of BHI 30 after 6 weeks of treatment≠0 hours

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7544
Comments A statistical significant threshold p<0.05
Method ANCOVA
Comments Treatment and strata as factors; baseline (week 0) value of duration of hypoglycaemic events as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.012
Confidence Interval 95%
-0.088 to 0.064
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Blood glucose below 2.5 mmol/l
12.Secondary Outcome
Title Hypoglycaemia Based on Self-reported Episodes
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consists of all randomised subjects who were exposed to at least one dose of trial product(s).
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
Overall Number of Participants Analyzed 71 73
Measure Type: Number
Unit of Measure: episodes
All 63 55
Major 3 3
Minor 9 10
Symptoms only 51 42
Time Frame The adverse events were collected in a time span of 6 weeks (starting from the start of treatment to the end of treatment plus one day)
Adverse Event Reporting Description The safety analysis set contains all randomised subjects exposed to at least one dose of trial drug(s).
 
Arm/Group Title BIAsp 30 BHI 30
Hide Arm/Group 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.
All-Cause Mortality
BIAsp 30 BHI 30
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BIAsp 30 BHI 30
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/71 (1.41%)      3/73 (4.11%)    
Injury, poisoning and procedural complications     
Soft tissue injury  1  0/71 (0.00%)  0 1/73 (1.37%)  1
Musculoskeletal and connective tissue disorders     
Loose body in joint  1  1/71 (1.41%)  1 0/73 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic cancer metastatic  1  0/71 (0.00%)  0 1/73 (1.37%)  1
Pancreatic carcinoma  1  0/71 (0.00%)  0 1/73 (1.37%)  1
Nervous system disorders     
Hypoglycaemic coma  1  0/71 (0.00%)  0 2/73 (2.74%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BIAsp 30 BHI 30
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/71 (0.00%)      0/73 (0.00%)    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Novo Nordisk reserves the right to not release data until specified milestones. This includes the right to not release interim results of clinical trials. At the end of the trial, manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00807092     History of Changes
Other Study ID Numbers: BIASP-3681
First Submitted: December 10, 2008
First Posted: December 11, 2008
Results First Submitted: November 12, 2010
Results First Posted: April 11, 2011
Last Update Posted: March 4, 2015