Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. The aim of this clinical trial is to compare NN5401 (insulin degludec/insulin aspart (IDegAsp)) with biphasic insulin aspart (BIAsp) 30 in patients with type 2 diabetes not optimally controlled on once or twice daily insulin with or without metformin.
Interventions
DRUGinsulin degludec/insulin aspart
Injected subcutaneously twice daily. Dose was individually adjusted.
DRUGbiphasic insulin aspart 30
Injected subcutaneously twice daily. Dose was individually adjusted.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female at least 18 years of age (at least 20 years for Japan) * Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months * Subject on basal human or analogue insulin, once daily (OD) or twice daily (BID) with or without metformin for at least 3 months or subject on premixed human or analogue insulin or self-mixed insulin regimen, containing 20-40% fast/rapid-acting component, OD or BID, with or without metformin, for at least 3 months * HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis * Body mass index (BMI) maximum 35.0 kg/m\^2
Exclusion criteria
* Treatment with oral antidiabetic drugs (OADs) (except metformin) within the last 8 weeks prior to Visit 1 * Treatment with thiazolidinediones (TZDs) or glucagon like peptide 1 (GLP-1) receptor agonists within 3 months prior to Visit 1 * Cardiovascular disease, within the last 6 months prior to Visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty * Uncontrolled treated/untreated severe hypertension (systolic blood pressure at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg) * Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements * Cancer and medical history of cancer (except basal cell skin cancer or squamous cell skin cancer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (Glycosylated Haemoglobin) After 26 Weeks of Treatment | Week 0, Week 26 | Change from baseline in HbA1c after 26 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 | Week 26 | Mean of SMPG at 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast. |
| Rate of Confirmed Hypoglycaemic Episodes | Week 0 to Week 26 + 7 days follow up | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol. |
| Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Week 0 to Week 26 + 7 days follow up | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m. |
| Change in Body Weight | Week 0, Week 26 | Change from baseline in body weight after 26 weeks of treatment. |
Countries
Hong Kong, Japan, Malaysia, South Korea, Taiwan
Participant flow
Recruitment details
The trial was conducted at 45 sites in 5 countries: Japan (16 sites), South Korea (16 sites), Hong Kong (1 site), Malaysia (8 sites) and Taiwan (4 sites).
Participants by arm
| Arm | Count |
|---|---|
| IDegAsp BID Insulin degludec/insulin aspart (IDegAsp) was given twice daily (BID) with breakfast and evening meal with or without metformin. | 280 |
| BIAsp 30 BID Biphasic insulin aspart (BIAsp 30) was given twice daily (BID) with breakfast and evening meal with or without metformin. | 142 |
| Total | 422 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 5 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Unclassified | 14 | 4 |
| Overall Study | Withdrawal Criteria | 9 | 4 |
Baseline characteristics
| Characteristic | IDegAsp BID | BIAsp 30 BID | Total |
|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 10.2 | 61.2 years STANDARD_DEVIATION 9.5 | 59.8 years STANDARD_DEVIATION 10 |
| Body weight at randomisation | 66.1 kg STANDARD_DEVIATION 11.2 | 66.0 kg STANDARD_DEVIATION 11.2 | 66.0 kg STANDARD_DEVIATION 11.2 |
| Fasting plasma glucose (FPG) | 7.9 mmol/L STANDARD_DEVIATION 2.5 | 7.9 mmol/L STANDARD_DEVIATION 2.5 | 7.9 mmol/L STANDARD_DEVIATION 2.5 |
| Glycosylated haemoglobin (HbA1c) | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 129 Participants | 63 Participants | 192 Participants |
| Sex: Female, Male Male | 151 Participants | 79 Participants | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 279 | 39 / 141 |
| serious Total, serious adverse events | 23 / 279 | 12 / 141 |
Outcome results
Primary
Change in HbA1c (Glycosylated Haemoglobin) After 26 Weeks of Treatment
Change from baseline in HbA1c after 26 weeks of treatment.
Time frame: Week 0, Week 26
Population: The full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp BID | Change in HbA1c (Glycosylated Haemoglobin) After 26 Weeks of Treatment | -1.38 percentage of glycosylated haemoglobin | Standard Deviation 0.88 |
| BIAsp 30 BID | Change in HbA1c (Glycosylated Haemoglobin) After 26 Weeks of Treatment | -1.42 percentage of glycosylated haemoglobin | Standard Deviation 0.97 |
Secondary
Change in Body Weight
Change from baseline in body weight after 26 weeks of treatment.
Time frame: Week 0, Week 26
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 |
|---|---|---|---|
| IDegAsp BID | Change in Body Weight | 1.1 kg | Standard Deviation 2.9 |
| BIAsp 30 BID | Change in Body Weight | 1.4 kg | Standard Deviation 3 |
Secondary
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26
Mean of SMPG at 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.
Time frame: Week 26
Population: The full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). For 24 subjects all 9-point SMPG values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp BID | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 | 7.6 mmol/L | Standard Deviation 1.7 |
| BIAsp 30 BID | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 | 7.9 mmol/L | Standard Deviation 1.8 |
Secondary
Rate of Confirmed Hypoglycaemic Episodes
Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol.
Time frame: Week 0 to Week 26 + 7 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 | Value (NUMBER) |
|---|---|---|
| IDegAsp BID | Rate of Confirmed Hypoglycaemic Episodes | 956 Episodes/100 years of patient exposure |
| BIAsp 30 BID | Rate of Confirmed Hypoglycaemic Episodes | 952 Episodes/100 years of patient exposure |
Secondary
Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m.
Time frame: Week 0 to Week 26 + 7 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 | Value (NUMBER) |
|---|---|---|
| IDegAsp BID | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 111 Episodes/100 years of patient exposure |
| BIAsp 30 BID | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 155 Episodes/100 years of patient exposure |