Trial Outcomes & Findings for A Trial Comparing the Efficacy of Insulin Degludec With Insulin Glargine on Glycaemic Control Using Continuous Glucose Monitoring in Patients With Type 1 Diabetes (NCT NCT01569841)
NCT ID: NCT01569841
Last Updated: 2016-02-18
Results Overview
Time within the glycaemic target range \[\> 70 mg/dL (3.9 mmol/L) and \< 130 mg/dL (7.2 mmol/L)\] measured by Continuous Glucose Monitoring (CGM) in the last four hours of each dosing interval during the last 2 weeks of the 6-week treatment period.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
24 participants
Primary outcome timeframe
CGM occured during the last 2 weeks of the 6 weeks treatment period.
Results posted on
2016-02-18
Participant Flow
The trial was conducted at one site in the United States of America (USA).
All subjects were on basal-bolus insulin regimens at screening using insulin glargine (IGlar) and either insulin aspart (IAsp) or insulin lispro (ILis). During the run-in period, IGlar 100 U/mL was administered subcutaneously (under the skin) once daily (OD) in the morning (before breakfast) along with IAsp 100 U/mL as meal-time insulin.
Participant milestones
| Measure |
IDeg/IGlar
The trial included 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
All randomised subjects were scheduled for 12 weeks of treatment with the trial products. After 6 weeks of treatment in period A, the subjects were crossed over to 6 weeks of the other treatment in period B.
Upon completing the 4-week run-in period, subjects randomised to the IDeg/IGlar treatment sequence received an morning dose of IDeg OD (100 U/mL, 3 mL prefilled pen) along with mealtime dosing of IAsp (100 U/mL, prefilled pen) subcutaneously (under the skin) for 6 weeks in treatment period A. Upon completion of treatment Period A, subjects crossed over to Period B and received a morning dose of IGlar OD (100 U/mL, SoloStar® prefilled pen) in combination with mealtime dosing of IAsp (100 U/mL, prefilled pen) subcutaneously (under the skin) for 6 weeks.
|
IGlar/IDeg
The trial included 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
All randomised subjects were scheduled for 12 weeks of treatment with the trial products. After 6 weeks of treatment in period A, the subjects were crossed over to 6 weeks of the other treatment in period B.
Upon completing the 4-week run-in period, subjects randomised to the IGlar/IDeg treatment sequence received an morning dose of IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen) subcutaneously (under the skin) in combination with mealtime dosing of IAsp (100 U/mL, prefilled pen) for 6 weeks in treatment Period A. Upon completion of treatment Period A, subjects crossed over to Period B and received a morning dose of IDeg OD (100 U/mL, 3 mL prefilled pen) subcutaneously (under the skin) in combination with mealtime dosing of IAsp (100 U/mL, prefilled pen) for 6 weeks.
|
|---|---|---|
|
Period A (6 Weeks)
STARTED
|
12
|
12
|
|
Period A (6 Weeks)
Exposed
|
12
|
12
|
|
Period A (6 Weeks)
COMPLETED
|
12
|
11
|
|
Period A (6 Weeks)
NOT COMPLETED
|
0
|
1
|
|
Period B (6 Weeks)
STARTED
|
12
|
11
|
|
Period B (6 Weeks)
Exposed
|
12
|
11
|
|
Period B (6 Weeks)
COMPLETED
|
12
|
11
|
|
Period B (6 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
IDeg/IGlar
The trial included 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
All randomised subjects were scheduled for 12 weeks of treatment with the trial products. After 6 weeks of treatment in period A, the subjects were crossed over to 6 weeks of the other treatment in period B.
Upon completing the 4-week run-in period, subjects randomised to the IDeg/IGlar treatment sequence received an morning dose of IDeg OD (100 U/mL, 3 mL prefilled pen) along with mealtime dosing of IAsp (100 U/mL, prefilled pen) subcutaneously (under the skin) for 6 weeks in treatment period A. Upon completion of treatment Period A, subjects crossed over to Period B and received a morning dose of IGlar OD (100 U/mL, SoloStar® prefilled pen) in combination with mealtime dosing of IAsp (100 U/mL, prefilled pen) subcutaneously (under the skin) for 6 weeks.
|
IGlar/IDeg
The trial included 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
All randomised subjects were scheduled for 12 weeks of treatment with the trial products. After 6 weeks of treatment in period A, the subjects were crossed over to 6 weeks of the other treatment in period B.
Upon completing the 4-week run-in period, subjects randomised to the IGlar/IDeg treatment sequence received an morning dose of IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen) subcutaneously (under the skin) in combination with mealtime dosing of IAsp (100 U/mL, prefilled pen) for 6 weeks in treatment Period A. Upon completion of treatment Period A, subjects crossed over to Period B and received a morning dose of IDeg OD (100 U/mL, 3 mL prefilled pen) subcutaneously (under the skin) in combination with mealtime dosing of IAsp (100 U/mL, prefilled pen) for 6 weeks.
|
|---|---|---|
|
Period A (6 Weeks)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Trial Comparing the Efficacy of Insulin Degludec With Insulin Glargine on Glycaemic Control Using Continuous Glucose Monitoring in Patients With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
Full Analysis Set
n=24 Participants
The full analysis set (FAS) included all randomised subjects.
|
|---|---|
|
Age, Continuous
|
45.3 years
STANDARD_DEVIATION 14.9 • n=99 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
|
Fasting Plasma Glucose (FPG)
|
10.7 mmol/L
STANDARD_DEVIATION 3.4 • n=99 Participants
|
|
Glycosylated Haemoglobin (HbA1c)
|
7.1 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=99 Participants
|
PRIMARY outcome
Timeframe: CGM occured during the last 2 weeks of the 6 weeks treatment period.Population: The FAS included all randomised subjects. One subject from the IGlar to IDeg treatment sequence withdrew from the trial during treatment period A while taking IGlar.
Time within the glycaemic target range \[\> 70 mg/dL (3.9 mmol/L) and \< 130 mg/dL (7.2 mmol/L)\] measured by Continuous Glucose Monitoring (CGM) in the last four hours of each dosing interval during the last 2 weeks of the 6-week treatment period.
Outcome measures
| Measure |
IDeg
n=23 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=23 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Average Time Within Glycaemic Target Range (Above 70 mg/dL and Below 130 mg/dL)
|
1.39 hours
Standard Deviation 0.71
|
1.09 hours
Standard Deviation 0.77
|
SECONDARY outcome
Timeframe: CGM monitoring occurred during the last 2 weeks of the 6-week treatment period.Population: The FAS included all randomised subjects. One subject from the IGlar to IDeg treatment sequence withdrew from the trial during treatment period A while taking IGlar.
The observed mean of IG profile was obtained as the average value of area under the IG profile divided by the actual assessment time interval during the last 2 weeks of the 6-week treatment period.
Outcome measures
| Measure |
IDeg
n=23 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=23 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Mean Interstitial Glucose (IG) Based on 14 Days of CGM
|
9.6 mmol/L
Standard Deviation 1.5
|
9.8 mmol/L
Standard Deviation 1.7
|
SECONDARY outcome
Timeframe: At the end of each 6 week treatment period.Population: The FAS included all randomised subjects. One subject from the IGlar to IDeg treatment sequence withdrew from the trial during treatment period A while taking IGlar.
FPG after 6 weeks of treatment in each treatment period.
Outcome measures
| Measure |
IDeg
n=12 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=11 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Fasting Plasma Glucose (FPG)
Treatment period A
|
8.8 mmol/L
Standard Deviation 4.6
|
10.9 mmol/L
Standard Deviation 4.8
|
|
Fasting Plasma Glucose (FPG)
Treatment period B
|
10.4 mmol/L
Standard Deviation 3.4
|
10.9 mmol/L
Standard Deviation 4.4
|
SECONDARY outcome
Timeframe: At the end of each 6 week treatment period.Population: The FAS included all randomised subjects. One subject from the IGlar to IDeg treatment sequence withdrew from the trial during treatment period A while taking IGlar.
HbA1c after 6 weeks of treatment in each treatment period.
Outcome measures
| Measure |
IDeg
n=12 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=11 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Glycosylated Haemoglobin (HbA1c)
Treatment period A
|
6.6 percentage of glycosylated haemoglobin
Standard Deviation 0.5
|
7.1 percentage of glycosylated haemoglobin
Standard Deviation 0.6
|
|
Glycosylated Haemoglobin (HbA1c)
Treatment period B
|
6.9 percentage of glycosylated haemoglobin
Standard Deviation 0.7
|
7.3 percentage of glycosylated haemoglobin
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: Within each week 6 treatment periodPopulation: 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). An AE was defined as treatment emergent if the onset date was on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Severity was assessed by investigator.
Outcome measures
| Measure |
IDeg
n=23 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=24 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Number of Treatment Emergent Adverse Events (AEs)
Adverse Events
|
18 events
|
16 events
|
|
Number of Treatment Emergent Adverse Events (AEs)
Serious Adverse Events
|
0 events
|
0 events
|
|
Number of Treatment Emergent Adverse Events (AEs)
Severe Adverse Events
|
3 events
|
0 events
|
|
Number of Treatment Emergent Adverse Events (AEs)
Moderate Adverse Events
|
5 events
|
0 events
|
|
Number of Treatment Emergent Adverse Events (AEs)
Mild Adverse Events
|
10 events
|
16 events
|
|
Number of Treatment Emergent Adverse Events (AEs)
Fatal Adverse Events
|
0 events
|
0 events
|
SECONDARY outcome
Timeframe: Hypoglycemic episodes reported within each 6 week treatment period.Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator.
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred after the first administration of investigational medicinal product (IMP), and no later than 7 days after the last day on trial product. Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia or minor hypoglycaemic episodes. Severe hypoglycaemic episodes: requiring assistance to administer carbohydrate, glucagon or other resuscitative actions. Minor hypoglycaemic episodes: able to treat her/himself and plasma glucose below 3.1 mmol/L.
Outcome measures
| Measure |
IDeg
n=23 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=24 Participants
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes
|
283 events
|
239 events
|
Adverse Events
IDeg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
IGlar
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
IDeg
n=23 participants at risk
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to insulin degludec (IDeg) OD (100 U/mL, 3 mL prefilled pen, morning dose) administered subcutaneously (under the skin) in combination with mealtime IAsp (100 U/mL, pre-filled pen) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IGlar OD (100 U/mL, SoloStar® prefilled pen, morning dose) in combination with mealtime IAsp (100 U/mL, s.c., prefilled pen) for 6 weeks.
|
IGlar
n=24 participants at risk
The trial included a screening period of approximately one week, a run-in period of 4 weeks followed by 2 treatment periods of 6 weeks each in a cross-over design, and a follow-up visit no less than 7 days after the last treatment visit. Total trial duration for the individual subject was 18 weeks.
Treatment period A: Subjects from run-in period were randomised to IGlar OD (100 U/mL, 3 mL SoloStar® prefilled pen s.c., morning dose) in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
Treatment period B: Subjects (from treatment period A) were crossed over to IDeg OD (100 U/mL, prefilled pen s.c., morning dose) for 6 weeks in combination with mealtime IAsp (100 U/mL, prefilled pen s.c.) for 6 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/23 • Treatment emergent adverse events were collected during each 6 week treatment period + 7 days follow up.
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
|
33.3%
8/24 • Number of events 8 • Treatment emergent adverse events were collected during each 6 week treatment period + 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 plans by any investigator to publish 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 Novo Nordisk before submission for comments. Comments will be given within four weeks from receipt of the planned communication.
- Publication restrictions are in place
Restriction type: OTHER