Diabetes, Diabetes Mellitus, Type 1
Conditions
Brief summary
This trial is conducted in the United States of America (USA). The aim of this trial is to compare the efficacy of insulin decludec with insulin glargine on glycaemic control using continuous glucose monitoring in patients with type 1 diabetes.
Interventions
DRUGinsulin degludec
Administered subcutaneously (s.c., under the skin) once daily.
DRUGinsulin glargine
Administered subcutaneously (s.c., under the skin) once daily.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes * HbA1c (glycosylated haemoglobin) below or equal to 8.5% * Current treatment with IGlar (insulin glargine) in a basal-bolus regimen with a total daily dose below 120 U * BMI (body mass index) below 35 kg/m\^2
Exclusion criteria
* Use within the last 3 months prior to visit 1 (screening) of any antidiabetic glucose lowering drug other than insulin/insulin analogues * Subjects with regular use of acetaminophen who are not willing to use another analgetic during CGM (Continuous Glucose Monitoring) periods * Stroke; heart failure; myocardial infarction; unstable angina pectoris; coronary arterial bypass graft or angioplasty within 24 weeks prior to visit 1 * Recurrent severe hypoglycemia (more than one severe hypoglycemic event during the last 12 months) or hypoglycemia unawareness or hospitalization for diabetic ketoacidosis during the previous 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Time Within Glycaemic Target Range (Above 70 mg/dL and Below 130 mg/dL) | CGM occured during the last 2 weeks of the 6 weeks treatment period. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Interstitial Glucose (IG) Based on 14 Days of CGM | CGM monitoring occurred during the last 2 weeks of the 6-week treatment period. | 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. |
| Fasting Plasma Glucose (FPG) | At the end of each 6 week treatment period. | FPG after 6 weeks of treatment in each treatment period. |
| Glycosylated Haemoglobin (HbA1c) | At the end of each 6 week treatment period. | HbA1c after 6 weeks of treatment in each treatment period. |
| Number of Treatment Emergent Adverse Events (AEs) | Within each week 6 treatment period | 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. |
| Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | Hypoglycemic episodes reported within each 6 week treatment period. | 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. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at one site in the United States of America (USA).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Full Analysis Set The full analysis set (FAS) included all randomised subjects. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period A (6 Weeks) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Full Analysis Set |
|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 14.9 |
| Fasting Plasma Glucose (FPG) | 10.7 mmol/L STANDARD_DEVIATION 3.4 |
| Glycosylated Haemoglobin (HbA1c) | 7.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.6 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 8 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
Primary
Average Time Within Glycaemic Target Range (Above 70 mg/dL and Below 130 mg/dL)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Average Time Within Glycaemic Target Range (Above 70 mg/dL and Below 130 mg/dL) | 1.39 hours | Standard Deviation 0.71 |
| IGlar | Average Time Within Glycaemic Target Range (Above 70 mg/dL and Below 130 mg/dL) | 1.09 hours | Standard Deviation 0.77 |
Secondary
Fasting Plasma Glucose (FPG)
FPG after 6 weeks of treatment in each treatment period.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDeg | Fasting Plasma Glucose (FPG) | Treatment period A | 8.8 mmol/L | Standard Deviation 4.6 |
| IDeg | Fasting Plasma Glucose (FPG) | Treatment period B | 10.4 mmol/L | Standard Deviation 3.4 |
| IGlar | Fasting Plasma Glucose (FPG) | Treatment period A | 10.9 mmol/L | Standard Deviation 4.8 |
| IGlar | Fasting Plasma Glucose (FPG) | Treatment period B | 10.9 mmol/L | Standard Deviation 4.4 |
Secondary
Glycosylated Haemoglobin (HbA1c)
HbA1c after 6 weeks of treatment in each treatment period.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDeg | Glycosylated Haemoglobin (HbA1c) | Treatment period A | 6.6 percentage of glycosylated haemoglobin | Standard Deviation 0.5 |
| IDeg | Glycosylated Haemoglobin (HbA1c) | Treatment period B | 6.9 percentage of glycosylated haemoglobin | Standard Deviation 0.7 |
| IGlar | Glycosylated Haemoglobin (HbA1c) | Treatment period A | 7.1 percentage of glycosylated haemoglobin | Standard Deviation 0.6 |
| IGlar | Glycosylated Haemoglobin (HbA1c) | Treatment period B | 7.3 percentage of glycosylated haemoglobin | Standard Deviation 0.6 |
Secondary
Mean Interstitial Glucose (IG) Based on 14 Days of CGM
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Mean Interstitial Glucose (IG) Based on 14 Days of CGM | 9.6 mmol/L | Standard Deviation 1.5 |
| IGlar | Mean Interstitial Glucose (IG) Based on 14 Days of CGM | 9.8 mmol/L | Standard Deviation 1.7 |
Secondary
Number of Treatment Emergent Adverse Events (AEs)
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.
Time frame: Within each week 6 treatment period
Population: The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IDeg | Number of Treatment Emergent Adverse Events (AEs) | Adverse Events | 18 events |
| IDeg | Number of Treatment Emergent Adverse Events (AEs) | Serious Adverse Events | 0 events |
| IDeg | Number of Treatment Emergent Adverse Events (AEs) | Severe Adverse Events | 3 events |
| IDeg | Number of Treatment Emergent Adverse Events (AEs) | Moderate Adverse Events | 5 events |
| IDeg | Number of Treatment Emergent Adverse Events (AEs) | Mild Adverse Events | 10 events |
| IDeg | Number of Treatment Emergent Adverse Events (AEs) | Fatal Adverse Events | 0 events |
| IGlar | Number of Treatment Emergent Adverse Events (AEs) | Mild Adverse Events | 16 events |
| IGlar | Number of Treatment Emergent Adverse Events (AEs) | Adverse Events | 16 events |
| IGlar | Number of Treatment Emergent Adverse Events (AEs) | Moderate Adverse Events | 0 events |
| IGlar | Number of Treatment Emergent Adverse Events (AEs) | Serious Adverse Events | 0 events |
| IGlar | Number of Treatment Emergent Adverse Events (AEs) | Fatal Adverse Events | 0 events |
| IGlar | Number of Treatment Emergent Adverse Events (AEs) | Severe Adverse Events | 0 events |
Secondary
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg | Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | 283 events |
| IGlar | Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | 239 events |