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A Trial Comparing the Efficacy, Patient-reported Outcomes and Safety of Insulin Degludec 200 U/mL vs Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Requiring High-dose Insulin

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ClinicalTrials.gov Identifier: NCT01570751
Recruitment Status : Completed
First Posted : April 4, 2012
Results First Posted : November 18, 2015
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: insulin degludec
Drug: insulin glargine
Enrollment 145
Recruitment Details The trial was conducted at 37 sites in the United States of America (USA).
Pre-assignment Details All subjects were on insulin glargine (IGlar, ≥ 65 U and ≤ 100 U/mL in 10 mL vials) treatment once daily (OD) administered subcutaneously at any time of day preferred by the subject for 16 week run-in period along with the daily pre-trial metformin dose.
Arm/Group Title IDeg/IGlar IGlar/IDeg
Hide Arm/Group Description The subjects in this arm for treatment period A received IDeg OD (200 U/mL in pre-filled pen device) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IGlar OD (100 U/mL in SoloStar® pen) for 16 weeks (treatment period B). Subjects were crossed over to IGlar without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit. The subjects in this arm for treatment period A received IGlar OD (100 U/mL in SoloStar® pen) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IDeg OD (200 U/mL in pre-filled pen device) for 16 weeks (treatment period B). Subjects were crossed over to IDeg without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit.
Period Title: Period A (16 Weeks)
Started 73 72
Exposed 73 72
Completed 70 67
Not Completed 3 5
Reason Not Completed
Protocol Violation             1             1
Withdrawal criteria             0             1
Unclassified             2             3
Period Title: Period B (16 Weeks)
Started 70 67
Exposed 70 67
Completed 69 66
Not Completed 1 1
Reason Not Completed
Adverse Event             1             0
Protocol Violation             0             1
Arm/Group Title IDeg/IGlar IGlar/IDeg Total
Hide Arm/Group Description The subjects in this arm for treatment period A received IDeg OD (200 U/mL in pre-filled pen device) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IGlar OD (100 U/mL in SoloStar® pen) for 16 weeks (treatment period B). Subjects were crossed over to IGlar without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit. The subjects in this arm for treatment period A received IGlar OD (100 U/mL in SoloStar® pen) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IDeg OD (200 U/mL in pre-filled pen device) for 16 weeks (treatment period B). Subjects were crossed over to IDeg without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit. Total of all reporting groups
Overall Number of Baseline Participants 73 72 145
Hide Baseline Analysis Population Description
For 4 subjects baseline fasting plasma glucose (FPG) values were missing, hence did not contribute to the FPG summary.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 73 participants 72 participants 145 participants
54.7  (10.2) 55.8  (9.0) 55.3  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 72 participants 145 participants
Female
31
  42.5%
24
  33.3%
55
  37.9%
Male
42
  57.5%
48
  66.7%
90
  62.1%
Glycosylated haemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated haemoglobin
Number Analyzed 73 participants 72 participants 145 participants
8.0  (1.1) 8.3  (1.4) 8.2  (1.3)
Fasting plasma glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 73 participants 72 participants 145 participants
7.5  (3.3) 8.5  (4.1) 8.0  (3.7)
1.Primary Outcome
Title Change From Baseline (Visit 18) in Glycosylated Haemoglobin (HbA1c) at the End of Each 16 Week Treatment Period
Hide Description Values for change in HbA1c after each 16 weeks of treatment periods A and B.
Time Frame Week 0, week 16 of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). For 7 subjects in IDeg treatment A and 7 subjects in IGlar treatment B, HbA1c values were missing at the period of baseline and did not contribute to the analysis.
Arm/Group Title IDeg IGlar
Hide Arm/Group Description:
Subjects received IDeg OD (200 U/mL in prefilled pen device) subcutaneously (under the skin) for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IGlar, subjects either received IDeg in treatment period A or treatment period B.
Subjects received IGlar OD (100 U/mL in Solostar® pen) subcutaneously (under the skin)for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IDeg, subjects either received IGlar in treatment period A or treatment period B.
Overall Number of Participants Analyzed 138 138
Mean (Standard Deviation)
Unit of Measure: percentage of glycosylated haemoglobin
-0.1  (1.1) -0.1  (1.1)
2.Secondary Outcome
Title Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period
Hide Description Changes in subjects quality of life and insulin device satisfaction were evaluated using the following PROs: the Short-Form 36 Health Survey version 2 (SF-36) and the Treatment Related Impact Measure–Diabetes Device (TRIM-DD). PRO total scores were measured from baseline to the end of each 16-week treatment period. Responses were measured on a scale of 0 to 100, where higher scores indicated a better quality of life and higher insulin device satisfaction on the SF-36 and TRIM-DD questionnaires, respectively.
Time Frame Week 0, week 16 of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF. For 8 subjects in each treatment group the values were missing at the period of baseline and did not contribute to the analysis.
Arm/Group Title IDeg IGlar
Hide Arm/Group Description:
Subjects received IDeg OD (200 U/mL in prefilled pen device) subcutaneously (under the skin) for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IGlar, subjects either received IDeg in treatment period A or treatment period B.
Subjects received IGlar OD (100 U/mL in Solostar® pen) subcutaneously (under the skin)for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IDeg, subjects either received IGlar in treatment period A or treatment period B.
Overall Number of Participants Analyzed 137 137
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Physical score -0.8  (7.7) -0.6  (7.8)
Mental score 0.7  (9.3) 0.4  (10.4)
Total D-device 11.0  (19.1) 3.5  (19.1)
3.Secondary Outcome
Title Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
Hide Description SF-36 and TRIM-DD total scores were measured at the end of treatment A (week 16) and 4 weeks into treatment B (week 20). Responses were measured on a scale of 0 to 100, where higher scores indicated a better quality of life and higher insulin device satisfaction on the SF-36 and TRIM-DD questionnaires, respectively.
Time Frame Week 16, week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. For 10 subjects, the PRO scores were missing.
Arm/Group Title IDeg/IGlar IGlar/IDeg
Hide Arm/Group Description:
The subjects in this arm for treatment period A received IDeg OD (200 U/mL in pre-filled pen device) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IGlar OD (100 U/mL in SoloStar® pen) for 16 weeks (treatment period B). Subjects were crossed over to IGlar without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit.
The subjects in this arm for treatment period A received IGlar OD (100 U/mL in SoloStar® pen) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IDeg OD (200 U/mL in pre-filled pen device) for 16 weeks (treatment period B). Subjects were crossed over to IDeg without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit.
Overall Number of Participants Analyzed 69 66
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Physical score 0.02  (7.07) 0.60  (6.09)
Mental score 0.61  (8.88) 0.21  (8.59)
Total D-device 10.24  (19.89) -6.25  (11.10)
4.Secondary Outcome
Title Change From Baseline in Central Laboratory Measured Fasting Plasma Glucose (FPG) at the End of Each 16 Week Treatment Period
Hide Description Values of FPG in mmol/L from baseline to each 16 weeks of treatment periods.
Time Frame Week 0, week 16, week 32
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF. For 17 subjects in IDeg treatment A and 16 subjects in IGlar treatment B, FPG values were missing at the period of baseline and did not contribute to the analysis.
Arm/Group Title IDeg IGlar
Hide Arm/Group Description:
Subjects received IDeg OD (200 U/mL in prefilled pen device) subcutaneously (under the skin) for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IGlar, subjects either received IDeg in treatment period A or treatment period B.
Subjects received IGlar OD (100 U/mL in Solostar® pen) subcutaneously (under the skin)for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IDeg, subjects either received IGlar in treatment period A or treatment period B.
Overall Number of Participants Analyzed 128 129
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.8  (4.2) -0.0  (4.4)
5.Secondary Outcome
Title Change in FPG From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
Hide Description Values of FPG in mmol/L from the end of treatment period A until after 4 weeks of treatment in treatment period B.
Time Frame Week 16, week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF. For 19 subjects the FPG values were missing.
Arm/Group Title IDeg/IGlar IGlar/IDeg
Hide Arm/Group Description:
The subjects in this arm for treatment period A received IDeg OD (200 U/mL in pre-filled pen device) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IGlar OD (100 U/mL in SoloStar® pen) for 16 weeks (treatment period B). Subjects were crossed over to IGlar without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit.
The subjects in this arm for treatment period A received IGlar OD (100 U/mL in SoloStar® pen) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IDeg OD (200 U/mL in pre-filled pen device) for 16 weeks (treatment period B). Subjects were crossed over to IDeg without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit.
Overall Number of Participants Analyzed 63 63
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.78  (3.41) 0.19  (4.40)
6.Secondary Outcome
Title Number of Adverse Events (AEs)
Hide Description Number of treatment emergent adverse events (TEAEs) from week 0 to week 16 of the randomised treatment periods. A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. TEAEs were attributed to the treatment given in the period in which the event occurred.
Time Frame From baseline to the end of each 16 week treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.
Arm/Group Title IDeg IGlar
Hide Arm/Group Description:
Subjects received IDeg OD (200 U/mL in prefilled pen device) subcutaneously (under the skin) for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IGlar, subjects either received IDeg in treatment period A or treatment period B.
Subjects received IGlar OD (100 U/mL in Solostar® pen) subcutaneously (under the skin)for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IDeg, subjects either received IGlar in treatment period A or treatment period B.
Overall Number of Participants Analyzed 140 142
Measure Type: Number
Unit of Measure: events
105 111
Time Frame The adverse events were collected in a time frame of 32 weeks + 7 days follow up
Adverse Event Reporting Description The SAS included all subjects who received at least one dose of the investigational product or its comparator.
 
Arm/Group Title IDeg IGlar
Hide Arm/Group Description Subjects received IDeg OD (200 U/mL in prefilled pen device) subcutaneously (under the skin) for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IGlar, subjects either received IDeg in treatment period A or treatment period B. Subjects received IGlar OD (100 U/mL in Solostar® pen) subcutaneously (under the skin)for 16 weeks in combination with metformin (pre-trial dose). As this was a 32-week cross-over trial with IDeg, subjects either received IGlar in treatment period A or treatment period B.
All-Cause Mortality
IDeg IGlar
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IDeg IGlar
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/140 (2.86%)      4/142 (2.82%)    
Cardiac disorders     
Acute coronary syndrome  1  0/140 (0.00%)  0 1/142 (0.70%)  1
Angina unstable  1  1/140 (0.71%)  1 0/142 (0.00%)  0
Infections and infestations     
Mastoiditis  1  1/140 (0.71%)  1 0/142 (0.00%)  0
Urinary tract infection  1  0/140 (0.00%)  0 1/142 (0.70%)  1
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/140 (0.71%)  1 0/142 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/140 (0.00%)  0 1/142 (0.70%)  1
Cervical spinal stenosis  1  1/140 (0.71%)  1 0/142 (0.00%)  0
Reproductive system and breast disorders     
Epididymitis  1  0/140 (0.00%)  0 1/142 (0.70%)  1
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  0/140 (0.00%)  0 1/142 (0.70%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IDeg IGlar
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/140 (1.43%)      9/142 (6.34%)    
Infections and infestations     
Nasopharyngitis  1  2/140 (1.43%)  2 9/142 (6.34%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Publications of Results:
Warren M, Chaykin L, Jabbour S, Sheikh-Ali M, Hansen CT, Rasmussen S, Norwood P. Efficacy, patient-reported outcomes (PRO) and safety of insulin degludec U200 vs insulin glargine in patients with type 2 diabetes (T2D) requiring high-dose insulin. Diabetes 2015; Suppl. 1 (64): A266 (Abstract 1040-P)
Warren M., Chaykin L.B., Jabbour S.,Sheikh-Ali M., Hansen C.T., Nielsen T.S.S., Norwood P.. Efficacy, patient-reported outcomes (PRO) and safety of insulin degludec U200 vs insulin glargine in patients with type 2 diabetes (T2D) requiring high-dose insulin. Diabetologia 2015; 58 (Suppl. 1): S468: (Abstract 968)
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01570751     History of Changes
Other Study ID Numbers: NN1250-3943
U1111-1123-4774 ( Other Identifier: WHO )
First Submitted: April 2, 2012
First Posted: April 4, 2012
Results First Submitted: October 16, 2015
Results First Posted: November 18, 2015
Last Update Posted: March 7, 2017