Diabetes, Diabetes Mellitus, Type 2
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/intermediate-acting insulin or pre-mixed insulin/pre-mixed insulin analogue on a twice daily regimen to NN5401 (SIAC, insulin degludec/insulin aspart) on a twice daily regimen in subjects with type 2 diabetes mellitus.
Interventions
DRUGinsulin degludec/insulin aspart
The insulin NN5401 (insulin degludec/insulin aspart) injected subcutaneously immediately before breakfast and dinner.
DRUGbiphasic insulin aspart 30
The insulin (biphasic insulin aspart 30) injected subcutaneously immediately before breakfast and dinner.
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 2 diabetes mellitus * Current treatment using a long-acting insulin analogue/intermediate-acting insulin preparation (except insulin glargine) or a pre-mixed insulin/insulin analogue preparation (except Mix30) on a twice daily regimen for at least 12 weeks, with stable insulin dose for the last 4 weeks (a brand of insulin preparation and dosing regimen has not been changed in the preceding 12 weeks) * HbA1c below 10.0% * Body Mass Index (BMI) \< 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 * Treatment with oral anti-diabetic drugs (OADs: including alpha-glucosidase inhibitor and insulin sensitizer \[thiazolidinedione: TZD\]) within the last 12 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Major and Minor Hypoglycaemic Episodes | Week 0 to Week 6 + 5 days follow up | 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 | 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 and 05:59 (both inclusive). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Electrocardiogram (ECG) Worsening | Week 0, Week 6 | The number of subjects having an 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 BP (Blood Pressure) | Week 0, Week 6. | Values at baseline (Week 0) and at Week 6 |
| Diastolic BP (Blood Pressure) | Week 0, Week 6 | Values at baseline (Week 0) and at Week 6 |
| Change in Body Weight | Week 0, Week 6 | Change from baseline in body weight after 6 weeks of treatment |
Countries
Japan
Participant flow
Recruitment details
A total of 8 sites in Japan
Participants by arm
| Arm | Count |
|---|---|
| SIAC Soluble insulin basal analogue combination (SIAC, 70 volume percent insulin degludec, 600 nmol/ml and 30 volume percent insulin aspart \[IAsp\], 600 nmol/ml) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted | 33 |
| Mix30 Biphasic insulin aspart (IAsp) 30 (Mix30) (i.e., 30% IAsp and 70% protamine-crystallised IAsp) was given subcutaneously twice daily immediately before breakfast and dinner for 6 weeks. Insulin doses were individually adjusted. | 32 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Unclassified | 0 | 2 |
Baseline characteristics
| Characteristic | SIAC | Mix30 | Total |
|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 8.4 | 64.7 years STANDARD_DEVIATION 11.2 | 64.5 years STANDARD_DEVIATION 9.8 |
| Body weight | 61.22 kg STANDARD_DEVIATION 9.88 | 57.32 kg STANDARD_DEVIATION 7.94 | 59.30 kg STANDARD_DEVIATION 9.12 |
| Fasting plasma glucose (FPG) | 144.6 mg/L STANDARD_DEVIATION 36.4 | 140.8 mg/L STANDARD_DEVIATION 38.6 | 142.7 mg/L STANDARD_DEVIATION 37.3 |
| Gender Female | 9 Participants | 14 Participants | 23 Participants |
| Gender Male | 24 Participants | 18 Participants | 42 Participants |
| Glycosylated haemoglobin (HbA1c) | 7.36 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.86 | 7.44 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.84 | 7.40 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.84 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 33 | 3 / 32 |
| serious Total, serious adverse events | 1 / 33 | 0 / 32 |
Outcome results
Primary
Rate of Major and Minor Hypoglycaemic Episodes
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) |
|---|---|---|---|
| SIAC | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| SIAC | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 13.63 Episodes /year of patient exposure |
| Mix30 | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| Mix30 | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 21.83 Episodes /year of patient exposure |
Primary
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
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 and 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) |
|---|---|---|---|
| SIAC | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
| SIAC | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 0.99 Episodes /year of patient exposure |
| Mix30 | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 2.03 Episodes /year of patient exposure |
| Mix30 | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes /year of patient exposure |
Secondary
Change in Body Weight
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. Missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIAC | Change in Body Weight | 0.09 kg | Standard Deviation 0.79 |
| Mix30 | Change in Body Weight | -0.10 kg | Standard Deviation 0.99 |
Secondary
Diastolic BP (Blood Pressure)
Values at baseline (Week 0) and at Week 6
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. Missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIAC | Diastolic BP (Blood Pressure) | Week 0 (Baseline) | 77.3 mmHg | Standard Deviation 11.1 |
| SIAC | Diastolic BP (Blood Pressure) | Week 6 | 76.8 mmHg | Standard Deviation 10.4 |
| Mix30 | Diastolic BP (Blood Pressure) | Week 0 (Baseline) | 75.4 mmHg | Standard Deviation 11.1 |
| Mix30 | Diastolic BP (Blood Pressure) | Week 6 | 76.7 mmHg | Standard Deviation 10 |
Secondary
Electrocardiogram (ECG) Worsening
The number of subjects having an 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. Missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SIAC | Electrocardiogram (ECG) Worsening | 2 participants |
| Mix30 | Electrocardiogram (ECG) Worsening | 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) |
|---|---|---|---|
| SIAC | Number of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 13 events |
| SIAC | Number of Treatment Emergent Adverse Events (AEs) | Severe AEs | 0 events |
| SIAC | Number of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 1 events |
| SIAC | Number of Treatment Emergent Adverse Events (AEs) | Mild AEs | 12 events |
| SIAC | Number of Treatment Emergent Adverse Events (AEs) | Serious AEs | 1 events |
| Mix30 | Number of Treatment Emergent Adverse Events (AEs) | Mild AEs | 8 events |
| Mix30 | Number of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 8 events |
| Mix30 | Number of Treatment Emergent Adverse Events (AEs) | Serious AEs | 0 events |
| Mix30 | Number of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 0 events |
| Mix30 | Number of Treatment Emergent Adverse Events (AEs) | Severe AEs | 0 events |
Secondary
Systolic BP (Blood Pressure)
Values at baseline (Week 0) and at Week 6
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. Missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIAC | Systolic BP (Blood Pressure) | Week 0 (Baseline) | 137.5 mmHg | Standard Deviation 15.5 |
| SIAC | Systolic BP (Blood Pressure) | Week 6 | 137.0 mmHg | Standard Deviation 17 |
| Mix30 | Systolic BP (Blood Pressure) | Week 0 (Baseline) | 130.8 mmHg | Standard Deviation 17.4 |
| Mix30 | Systolic BP (Blood Pressure) | Week 6 | 130.9 mmHg | Standard Deviation 16 |