Diabetes, Diabetes Mellitus, Type 1
Conditions
Brief summary
This trial is conducted in Japan. The aim of this clinical trial is to investigate the safety (with emphasis on hypoglycaemia) after switching from long-acting insulin analogue or intermediate-acting insulin to insulin degludec (NN1250, SIBA) on a basal-bolus regimen in subjects with type 1 diabetes mellitus.
Interventions
DRUGinsulin degludec
The insulin NN1250 (insulin degludec) injected subcutaneously at bedtime
DRUGinsulin detemir
Injection subcutaneously at bedtime
DRUGinsulin aspart
Injection subcutaneously immediately before each meal.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with type 1 diabetes mellitus more than one year * Current treatment: basal (once daily at bedtime) - bolus (three times a day just before main meals) regimen only for at least 12 weeks using a long-acting insulin analogue excluding insulin detemir or intermediate-acting insulin as a basal insulin and NovoRapid® as bolus insulin (a brand of basal insulin preparation has not been changed in the preceding 12 weeks) * HbA1c below 10.0% * Body Mass Index (BMI) below 30.0 kg/m\^2
Exclusion criteria
* Known hypoglycaemia unawareness or recurrent major hypoglycaemia * Current treatment with total insulin dose of more than 100 U or IU/day * Current treatment or expected to start treatment with systemic corticosteroid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Major and Minor Hypoglycaemic Episodes | Week 0 to Week 6 + 5 days follow up | Observed rate of major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL. |
| Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Week 0 to Week 6 + 5 days follow up | Observed rate of nocturnal major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL. Episodes were defined as nocturnal if the time of onset was between 23:00-05:59 (both inclusive). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Electrocardiogram (ECG) | Week 0, Week 6 | The number of subjects having a electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management. |
| Number of Treatment Emergent Adverse Events (AEs) | Week 0 to Week 6 + 5 days follow up | Corresponds to number of adverse events. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. |
| Systolic Blood Pressure (BP) | Week 0, Week 6 | Mean values at baseline (Week 0) and at Week 6 |
| Diastolic Blood Pressure (BP) | Week 0, Week 6 | Mean values at baseline (Week 0) and at Week 6 |
| Change in Body Weight | Week 0, Week 6 | Observed change from baseline in body weight after 6 weeks of treatment |
Countries
Japan
Participant flow
Recruitment details
A total of 8 sites in Japan
Pre-assignment details
The period between the Visit 1 (screening visit) and Visit 2 (baseline visit) of 3 weeks \[±7 days\] was the run-in period. The subjects continued their insulin treatment (basal-bolus therapy: insulin glargine or neutral protamine Hagedorn (intermediate-acting insulin) \[NPH\] insulin) same as their pre-trial dose.
Participants by arm
| Arm | Count |
|---|---|
| SIBA Soluble insulin basal analogue (SIBA, insulin degludec) was given subcutaneously once daily (OD) at bedtime and insulin aspart was given subcutaneously immediately before meals three times a day for 6 weeks. Insulin doses were individually adjusted. | 33 |
| Insulin Detemir Insulin detemir was given subcutaneously once daily (OD) at bedtime and insulin aspart was given subcutaneously immediately before meals three times a day for 6 weeks. Insulin doses were individually adjusted. | 32 |
| Total | 65 |
Baseline characteristics
| Characteristic | SIBA | Insulin Detemir | Total |
|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 15 | 43.2 years STANDARD_DEVIATION 15.4 | 44.4 years STANDARD_DEVIATION 15.1 |
| Body weight | 64.15 kg STANDARD_DEVIATION 11.11 | 62.28 kg STANDARD_DEVIATION 7.85 | 63.23 kg STANDARD_DEVIATION 9.61 |
| Fasting plasma glucose (FPG) | 181.8 mg/dL STANDARD_DEVIATION 66.2 | 141.8 mg/dL STANDARD_DEVIATION 54.3 | 162.1 mg/dL STANDARD_DEVIATION 63.4 |
| Glycosylated haemoglobin (HbA1c) | 7.39 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.86 | 7.32 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.86 | 7.35 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.86 |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 24 Participants | 19 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 33 | 2 / 32 |
| serious Total, serious adverse events | 0 / 33 | 0 / 32 |
Outcome results
Primary
Rate of Major and Minor Hypoglycaemic Episodes
Observed rate of major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL.
Time frame: Week 0 to Week 6 + 5 days follow up
Population: The Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIBA | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| SIBA | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 62.97 Episodes /year of patient exposure |
| Insulin Detemir | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| Insulin Detemir | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 80.84 Episodes /year of patient exposure |
Primary
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
Observed rate of nocturnal major and minor hypoglycaemic episodes per patient year (1year=365.25days) of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose ≤ 55 mg/dL. Episodes were defined as nocturnal if the time of onset was between 23:00-05:59 (both inclusive).
Time frame: Week 0 to Week 6 + 5 days follow up
Population: The Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIBA | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| SIBA | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 4.97 Episodes /year of patient exposure |
| Insulin Detemir | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| Insulin Detemir | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 15.83 Episodes /year of patient exposure |
Secondary
Change in Body Weight
Observed change from baseline in body weight after 6 weeks of treatment
Time frame: Week 0, Week 6
Population: The Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIBA | Change in Body Weight | 0.22 kg | Standard Deviation 1.02 |
| Insulin Detemir | Change in Body Weight | -0.20 kg | Standard Deviation 1.19 |
Secondary
Diastolic Blood Pressure (BP)
Mean values at baseline (Week 0) and at Week 6
Time frame: Week 0, Week 6
Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA | Diastolic Blood Pressure (BP) | Week 0 (Baseline) | 73.9 mmHg | Standard Deviation 7.8 |
| SIBA | Diastolic Blood Pressure (BP) | Week 6 | 74.7 mmHg | Standard Deviation 6.4 |
| Insulin Detemir | Diastolic Blood Pressure (BP) | Week 0 (Baseline) | 73.8 mmHg | Standard Deviation 9.3 |
| Insulin Detemir | Diastolic Blood Pressure (BP) | Week 6 | 73.0 mmHg | Standard Deviation 8 |
Secondary
Electrocardiogram (ECG)
The number of subjects having a electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.
Time frame: Week 0, Week 6
Population: The Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SIBA | Electrocardiogram (ECG) | 0 participants |
| Insulin Detemir | Electrocardiogram (ECG) | 0 participants |
Secondary
Number of Treatment Emergent Adverse Events (AEs)
Corresponds to number of adverse events. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.
Time frame: Week 0 to Week 6 + 5 days follow up
Population: The Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIBA | Number of Treatment Emergent Adverse Events (AEs) | Serious AEs | 0 events |
| SIBA | Number of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 0 events |
| SIBA | Number of Treatment Emergent Adverse Events (AEs) | Severe AEs | 0 events |
| SIBA | Number of Treatment Emergent Adverse Events (AEs) | Mild AEs | 13 events |
| SIBA | Number of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 13 events |
| Insulin Detemir | Number of Treatment Emergent Adverse Events (AEs) | Mild AEs | 13 events |
| Insulin Detemir | Number of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 15 events |
| Insulin Detemir | Number of Treatment Emergent Adverse Events (AEs) | Serious AEs | 0 events |
| Insulin Detemir | Number of Treatment Emergent Adverse Events (AEs) | Severe AEs | 0 events |
| Insulin Detemir | Number of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 2 events |
Secondary
Systolic Blood Pressure (BP)
Mean values at baseline (Week 0) and at Week 6
Time frame: Week 0, Week 6
Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA | Systolic Blood Pressure (BP) | Week 0 (Baseline) | 125.0 mmHg | Standard Deviation 15.5 |
| SIBA | Systolic Blood Pressure (BP) | Week 6 | 125.5 mmHg | Standard Deviation 13.3 |
| Insulin Detemir | Systolic Blood Pressure (BP) | Week 0 (Baseline) | 125.3 mmHg | Standard Deviation 16 |
| Insulin Detemir | Systolic Blood Pressure (BP) | Week 6 | 120.2 mmHg | Standard Deviation 13.8 |