Trial Outcomes & Findings for 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 (NCT NCT01570751)
NCT ID: NCT01570751
Last Updated: 2017-03-07
Results Overview
Values for change in HbA1c after each 16 weeks of treatment periods A and B.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
145 participants
Primary outcome timeframe
Week 0, week 16 of each treatment period.
Results posted on
2017-03-07
Participant Flow
The trial was conducted at 37 sites in the United States of America (USA).
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.
Participant milestones
| Measure |
IDeg/IGlar
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.
|
IGlar/IDeg
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 A (16 Weeks)
STARTED
|
73
|
72
|
|
Period A (16 Weeks)
Exposed
|
73
|
72
|
|
Period A (16 Weeks)
COMPLETED
|
70
|
67
|
|
Period A (16 Weeks)
NOT COMPLETED
|
3
|
5
|
|
Period B (16 Weeks)
STARTED
|
70
|
67
|
|
Period B (16 Weeks)
Exposed
|
70
|
67
|
|
Period B (16 Weeks)
COMPLETED
|
69
|
66
|
|
Period B (16 Weeks)
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
IDeg/IGlar
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.
|
IGlar/IDeg
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 A (16 Weeks)
Protocol Violation
|
1
|
1
|
|
Period A (16 Weeks)
Withdrawal criteria
|
0
|
1
|
|
Period A (16 Weeks)
Unclassified
|
2
|
3
|
|
Period B (16 Weeks)
Adverse Event
|
1
|
0
|
|
Period B (16 Weeks)
Protocol Violation
|
0
|
1
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
IDeg/IGlar
n=73 Participants
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.
|
IGlar/IDeg
n=72 Participants
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
n=145 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.7 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
55.8 years
STANDARD_DEVIATION 9.0 • n=7 Participants
|
55.3 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
|
Glycosylated haemoglobin (HbA1c)
|
8.0 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 1.1 • n=5 Participants
|
8.3 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 1.4 • n=7 Participants
|
8.2 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 1.3 • n=5 Participants
|
|
Fasting plasma glucose (FPG)
|
7.5 mmol/L
STANDARD_DEVIATION 3.3 • n=5 Participants
|
8.5 mmol/L
STANDARD_DEVIATION 4.1 • n=7 Participants
|
8.0 mmol/L
STANDARD_DEVIATION 3.7 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0, week 16 of each treatment period.Population: 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.
Values for change in HbA1c after each 16 weeks of treatment periods A and B.
Outcome measures
| Measure |
IDeg
n=138 Participants
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.
|
IGlar
n=138 Participants
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.
|
|---|---|---|
|
Change From Baseline (Visit 18) in Glycosylated Haemoglobin (HbA1c) at the End of Each 16 Week Treatment Period
|
-0.1 percentage of glycosylated haemoglobin
Standard Deviation 1.1
|
-0.1 percentage of glycosylated haemoglobin
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: Week 0, week 16 of each treatment period.Population: 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.
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.
Outcome measures
| Measure |
IDeg
n=137 Participants
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.
|
IGlar
n=137 Participants
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.
|
|---|---|---|
|
Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period
Physical score
|
-0.8 scores on a scale
Standard Deviation 7.7
|
-0.6 scores on a scale
Standard Deviation 7.8
|
|
Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period
Mental score
|
0.7 scores on a scale
Standard Deviation 9.3
|
0.4 scores on a scale
Standard Deviation 10.4
|
|
Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period
Total D-device
|
11.0 scores on a scale
Standard Deviation 19.1
|
3.5 scores on a scale
Standard Deviation 19.1
|
SECONDARY outcome
Timeframe: Week 16, week 20Population: The FAS included all randomised subjects. For 10 subjects, the PRO scores were missing.
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.
Outcome measures
| Measure |
IDeg
n=69 Participants
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.
|
IGlar
n=66 Participants
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.
|
|---|---|---|
|
Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
Physical score
|
0.02 scores on a scale
Standard Deviation 7.07
|
0.60 scores on a scale
Standard Deviation 6.09
|
|
Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
Mental score
|
0.61 scores on a scale
Standard Deviation 8.88
|
0.21 scores on a scale
Standard Deviation 8.59
|
|
Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
Total D-device
|
10.24 scores on a scale
Standard Deviation 19.89
|
-6.25 scores on a scale
Standard Deviation 11.10
|
SECONDARY outcome
Timeframe: Week 0, week 16, week 32Population: 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.
Values of FPG in mmol/L from baseline to each 16 weeks of treatment periods.
Outcome measures
| Measure |
IDeg
n=128 Participants
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.
|
IGlar
n=129 Participants
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.
|
|---|---|---|
|
Change From Baseline in Central Laboratory Measured Fasting Plasma Glucose (FPG) at the End of Each 16 Week Treatment Period
|
-0.8 mmol/L
Standard Deviation 4.2
|
-0.0 mmol/L
Standard Deviation 4.4
|
SECONDARY outcome
Timeframe: Week 16, week 20Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 19 subjects the FPG values were missing.
Values of FPG in mmol/L from the end of treatment period A until after 4 weeks of treatment in treatment period B.
Outcome measures
| Measure |
IDeg
n=63 Participants
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.
|
IGlar
n=63 Participants
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.
|
|---|---|---|
|
Change in FPG From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
|
-0.78 mmol/L
Standard Deviation 3.41
|
0.19 mmol/L
Standard Deviation 4.40
|
SECONDARY outcome
Timeframe: From baseline to the end of each 16 week treatment period.Population: The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.
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.
Outcome measures
| Measure |
IDeg
n=140 Participants
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.
|
IGlar
n=142 Participants
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.
|
|---|---|---|
|
Number of Adverse Events (AEs)
|
105 events
|
111 events
|
Adverse Events
IDeg
Serious events: 4 serious events
Other events: 2 other events
Deaths: 0 deaths
IGlar
Serious events: 4 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IDeg
n=140 participants at risk
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.
|
IGlar
n=142 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/140 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.70%
1/142 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Cardiac disorders
Angina unstable
|
0.71%
1/140 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.00%
0/142 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Infections and infestations
Mastoiditis
|
0.71%
1/140 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.00%
0/142 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/140 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.70%
1/142 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.71%
1/140 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.00%
0/142 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/140 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.70%
1/142 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.71%
1/140 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.00%
0/142 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Reproductive system and breast disorders
Epididymitis
|
0.00%
0/140 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.70%
1/142 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/140 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
0.70%
1/142 • Number of events 1 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
Other adverse events
| Measure |
IDeg
n=140 participants at risk
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.
|
IGlar
n=142 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
1.4%
2/140 • Number of events 2 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
6.3%
9/142 • Number of events 9 • The adverse events were collected in a time frame of 32 weeks + 7 days follow up
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER