Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen (Full STEP™)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01165684
Recruitment Status : Completed
First Posted : July 20, 2010
Results First Posted : June 11, 2013
Last Update Posted : February 17, 2017
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: insulin aspart
Drug: insulin detemir
Enrollment 401
Recruitment Details The trial was conducted at 69 sites in 7 countries: Argentina (7), Brazil (5), Canada (12), France (7), Macedonia (1), Slovenia (4), and the US (31). Of 12 sites in Canada, one site (Site 303) closed early on 07-Mar-2011.
Pre-assignment Details Subjects on pre-trial metformin and pioglitazone continued their medication.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication. In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Period Title: Overall Study
Started 201 200
Exposed 198 [1] 199 [2]
Completed 173 148
Not Completed 28 52
Reason Not Completed
Adverse Event             1             1
Lack of Efficacy             2             1
Protocol Violation             7             15
Withdrawal Criteria             2             13
Unclassified             16             22
[1]
3 subjects withdrew prior to exposure to trial drug
[2]
1 subject withdrew prior to exposure to trial drug
Arm/Group Title Step-wise Basal-bolus Total
Hide Arm/Group Description In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication. In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication. Total of all reporting groups
Overall Number of Baseline Participants 201 200 401
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 200 participants 401 participants
60.0  (9.1) 59.6  (9.5) 59.8  (9.3)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 200 participants 401 participants
Female
97
  48.3%
101
  50.5%
198
  49.4%
Male
104
  51.7%
99
  49.5%
203
  50.6%
Body weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 201 participants 200 participants 401 participants
88.9  (18.7) 86.1  (15.2) 87.5  (17.1)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 201 participants 200 participants 401 participants
31.5  (4.8) 30.7  (4.6) 31.1  (4.7)
Glycosylated haemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated haemoglobin
Number Analyzed 201 participants 200 participants 401 participants
7.9  (0.6) 7.9  (0.6) 7.9  (0.6)
Fasting plasma glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 201 participants 200 participants 401 participants
7.0  (1.9) 6.9  (1.6) 6.9  (1.8)
1.Primary Outcome
Title Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32
Hide Description Estimated mean change from baseline in HbA1c after 32 Weeks of treatment
Time Frame Week 0, Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 195 188
Mean (Standard Error)
Unit of Measure: percentage of glycosylated haemoglobin
-0.98  (0.06) -1.12  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was considered confirmed if the upper bound of the two-sided 95% CI was below or equal to 0.4% or equivalently if the p-value for the one-sided test of was less than or equal to 2.5%, where D is the mean treatment difference (step-wise regimen minus basal-bolus regimen).
Statistical Test of Hypothesis P-Value 0.088
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated treatment difference, Mean
Estimated Value 0.14
Confidence Interval 95%
-0.02 to 0.30
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10
Hide Description Estimated mean change from baseline in HbA1c after 10 Weeks of treatment
Time Frame Week 0, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 376 subjects contributed to the statistical analysis at Week 10.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 193 183
Mean (Standard Error)
Unit of Measure: percentage of glycosylated haemoglobin
-0.45  (0.05) -1.00  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated treatment difference, Mean
Estimated Value 0.55
Confidence Interval 95%
0.42 to 0.69
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21
Hide Description Estimated mean change from baseline in HbA1c after 21 Weeks of treatment
Time Frame Week 0, Week 21
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 21.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 195 188
Mean (Standard Error)
Unit of Measure: percentage of glycosylated haemoglobin
-0.78  (0.06) -1.15  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated treatment difference, Mean
Estimated Value 0.37
Confidence Interval 95%
0.21 to 0.53
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10
Hide Description Proportion of subjects reaching HbA1c below 7.0% at Week 10
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 376 subjects contributed to the statistical analysis at Week 10.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 193 183
Measure Type: Number
Unit of Measure: percentage (%) of subjects
19.2 56.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.85
Confidence Interval 95%
4.12 to 11.39
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21
Hide Description Proportion of subjects reaching HbA1c below 7.0% at Week 21
Time Frame Week 21
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 21.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 195 188
Measure Type: Number
Unit of Measure: percentage (%) of subjects
45.1 65.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.38
Confidence Interval 95%
1.56 to 3.64
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32
Hide Description Proportion of subjects reaching HbA1c below 7.0% at Week 32
Time Frame Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 195 188
Measure Type: Number
Unit of Measure: percentage (%) of subjects
55.9 63.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.146
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.36
Confidence Interval 95%
0.90 to 2.07
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Fasting Plasma Glucose (FPG) at Week 10
Hide Description Mean FPG at Week 10
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 368 subjects contributed to data at Week 10.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 186 182
Mean (Standard Deviation)
Unit of Measure: mmol/L
7.1  (1.9) 6.7  (1.9)
8.Secondary Outcome
Title Fasting Plasma Glucose (FPG) at Week 21
Hide Description Mean FPG at Week 21
Time Frame Week 21
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the data at Week 21.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 195 188
Mean (Standard Deviation)
Unit of Measure: mmol/L
7.1  (2.3) 7.0  (2.3)
9.Secondary Outcome
Title Fasting Plasma Glucose (FPG) at Week 32
Hide Description Estimated Mean FPG at Week 32
Time Frame Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 195 188
Mean (Standard Error)
Unit of Measure: mmol/L
7.12  (0.17) 7.01  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.635
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Mean
Estimated Value 0.12
Confidence Interval 95%
-0.37 to 0.60
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10
Hide Description Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 10
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 326 subjects contributed to the data at Week 10.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 165 161
Mean (Standard Deviation)
Unit of Measure: mmol/L
2.3  (2.2) 1.4  (2.0)
11.Secondary Outcome
Title Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21
Hide Description Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 21
Time Frame Week 21
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 343 subjects contributed to the data at Week 21.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 176 167
Mean (Standard Deviation)
Unit of Measure: mmol/L
1.9  (1.8) 1.5  (1.8)
12.Secondary Outcome
Title Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32
Hide Description Estimated mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 32
Time Frame Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 352 subjects contributed to the statistical analysis at Week 32.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 182 170
Mean (Standard Deviation)
Unit of Measure: mmol/L
1.64  (0.12) 1.28  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean
Estimated Value 0.36
Confidence Interval 95%
0.01 to 0.71
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Body Weight at Week 32
Hide Description Estimated mean body weight after 32 Weeks of treatment
Time Frame Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 378 subjects contributed to the statistical analysis at Week 32.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 190 188
Mean (Standard Error)
Unit of Measure: kg
89.32  (0.28) 89.80  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.228
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean
Estimated Value -0.48
Confidence Interval 95%
-1.25 to 0.30
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Body Mass Index (BMI) at Week 32
Hide Description Estimated mean BMI after 32 Weeks of treatment
Time Frame Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 378 subjects contributed to the statistical analysis at Week 32.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 190 188
Mean (Standard Error)
Unit of Measure: kg/m^2
31.86  (0.10) 32.03  (0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Step-wise, Basal-bolus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.224
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean
Estimated Value -0.17
Confidence Interval 95%
-0.45 to 0.11
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes)
Hide Description A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment.
Time Frame Week 0 to Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator. 397 subjects contributed with data.
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description:
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
Overall Number of Participants Analyzed 198 199
Measure Type: Number
Unit of Measure: Episodes /year of patient exposure
33.47 57.56
Time Frame Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Adverse Event Reporting Description Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
 
Arm/Group Title Step-wise Basal-bolus
Hide Arm/Group Description In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication. In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
All-Cause Mortality
Step-wise Basal-bolus
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Step-wise Basal-bolus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/198 (9.09%)      15/199 (7.54%)    
Cardiac disorders     
Acute myocardial infarction  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Atrial fibrillation  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Coronary artery disease  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Myocardial ischaemia  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Supraventricular tachycardia  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain upper  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Gastrointestinal fistula  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Intestinal obstruction  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Pancreatitis  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Hepatobiliary disorders     
Cholelithiasis  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Infections and infestations     
Bacterial translocation  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Erysipelas  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Gastroenteritis  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Injection site infection  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Pneumonia  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Pyelonephritis acute  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Injury, poisoning and procedural complications     
Intentional overdose  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Wrong drug administered  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Metabolism and nutrition disorders     
Hypoglycaemia  1  2/198 (1.01%)  3 5/199 (2.51%)  6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gallbladder cancer  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Metastases to liver  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Metastatic gastric cancer  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Hypoglycaemic seizure  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Hypoglycaemic unconsciousness  1  0/198 (0.00%)  0 3/199 (1.51%)  3
Psychiatric disorders     
Acute stress disorder  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Lower respiratory tract inflammation  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Vascular disorders     
Orthostatic hypotension  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Peripheral arterial occlusive disease  1  1/198 (0.51%)  1 0/199 (0.00%)  0
Peripheral vascular disorder  1  0/198 (0.00%)  0 1/199 (0.50%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Step-wise Basal-bolus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/198 (20.20%)      47/199 (23.62%)    
Gastrointestinal disorders     
Diarrhoea  1  8/198 (4.04%)  10 10/199 (5.03%)  10
General disorders     
Oedema peripheral  1  4/198 (2.02%)  5 10/199 (5.03%)  10
Infections and infestations     
Influenza  1  10/198 (5.05%)  11 13/199 (6.53%)  14
Nasopharyngitis  1  16/198 (8.08%)  19 13/199 (6.53%)  18
Nervous system disorders     
Headache  1  10/198 (5.05%)  15 11/199 (5.53%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
A higher proportion of subjects did not complete the trial in the basal-bolus arm (52 subjects, 26.0%) than in the step-wise arm (28 subjects, 13.9%).
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 maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Novo Nordisk reserves the right to prior review of such publications and to ask for delay of publication of individual site results until after the primary manuscript is accepted for publication.
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: NCT01165684     History of Changes
Other Study ID Numbers: ANA-3786
2010-018974-19 ( EudraCT Number )
U1111-1116-0908 ( Other Identifier: WHO )
First Submitted: July 16, 2010
First Posted: July 20, 2010
Results First Submitted: April 25, 2013
Results First Posted: June 11, 2013
Last Update Posted: February 17, 2017