Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Africa, Europe and the United States of America (USA). The aim of the trial is to compare the difference in change in glycosylated haemoglobin (HbA1c) between insulin degludec/insulin aspart (IDegAsp) and/or oral anti-diabetic drugs (OADs) and insulin degludec (IDeg) plus insulin aspart (IAsp)and/or OADs.
Interventions
DRUGinsulin degludec/insulin aspart
Dose individually adjusted. For subcutaneous (s.c, under the skin) administration twice a day.
DRUGinsulin degludec
Dose individually adjusted. For subcutaneous (s.c, under the skin) administration once daily.
DRUGinsulin aspart
Dose individually adjusted. For subcutaneous (s.c, under the skin) administration with the main meals 2-4 times daily in accordance with local labelling.
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
* Diagnosis of type 2 Diabetes Mellitus at the discretion of the investigator for at least 26 weeks prior to screening (visit 1) * Treatment with basal insulin for at least 12 weeks prior to randomisation with or without metformin, sulphonylurea (SU)/glinide, DPP-4 inhibitors, alfa-glucosidase-inhibitors * HbA1c 7.0% - 10.0% * Body mass index (BMI) less than or equal to 40.0 kg/m\^2
Exclusion criteria
* Treatment with glucose-lowering agent(s) other than those stated in the inclusion criteria * Stroke; heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty * Chronic disorder or disease which might jeopardise safety or compliance * Malignant neoplasms * Recurrent severe hypoglycaemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (%) | Week 0, week 26 | Change from baseline in HbA1c (%) after 26 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) | Week 0, week 26 | Change from baseline in FPG after 26 weeks of treatment |
| Number of Treatment Emergent Hypoglycaemic Episodes | During Weeks 0-26 | According to the Novo Nordisk definition for confirmed hypoglycaemic episodes (severe hypoglycaemia and/or a measured Plasma Glucose (PG) \<3.1 mmol/L(56 mg/dL)) |
| Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes | Weeks 0-26 | Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m. |
| Incidence of Treatment Emergent Adverse Events (TEAE) | Weeks 0-26 | A TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment |
Countries
Algeria, Austria, France, Norway, United States
Participant flow
Recruitment details
The trial was conducted in 5 countries (48 sites): Algeria (4), Austria (6), France (8), Norway (6) and United States (24).
Participants by arm
| Arm | Count |
|---|---|
| IDegAsp BID The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening). | 138 |
| IDeg OD+IAsp The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp (\[NovoRapid®/NovoLog®\], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling.
The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1. | 136 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 |
| Overall Study | Unclassified | 4 | 2 |
| Overall Study | Withdrawal criteria | 21 | 12 |
Baseline characteristics
| Characteristic | IDegAsp BID | IDeg OD+IAsp | Total |
|---|---|---|---|
| Age, Continuous Age | 59.6 years STANDARD_DEVIATION 8.3 | 59.6 years STANDARD_DEVIATION 9.2 | 59.6 years STANDARD_DEVIATION 8.7 |
| Fasting plasma glucose | 9.0 mmol/L STANDARD_DEVIATION 3 | 8.8 mmol/L STANDARD_DEVIATION 2.9 | 8.9 mmol/L STANDARD_DEVIATION 3 |
| Glycosylated haemoglobin (HbA1c) | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 65 Participants | 50 Participants | 115 Participants |
| Sex: Female, Male Male | 73 Participants | 86 Participants | 159 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 136 | 38 / 135 |
| serious Total, serious adverse events | 7 / 136 | 13 / 135 |
Outcome results
Primary
Change From Baseline in HbA1c (%)
Change from baseline in HbA1c (%) after 26 weeks of treatment
Time frame: Week 0, week 26
Population: The FAS included all randomised subjects. The statistical evaluation of the FAS followed the ITT principle and subjects contributed to the evaluation as randomised.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp BID | Change From Baseline in HbA1c (%) | -1.23 percentage change in HbA1c | Standard Error 0.13 |
| IDeg OD+IAsp | Change From Baseline in HbA1c (%) | -1.42 percentage change in HbA1c | Standard Error 0.12 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline in FPG after 26 weeks of treatment
Time frame: Week 0, week 26
Population: The FAS included all randomised subjects (2 subjects-baseline FPG not measured). The statistical evaluation of the FAS followed the ITT principle and subjects contributed to the evaluation as randomised.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp BID | Change From Baseline in Fasting Plasma Glucose (FPG) | -2.22 mmol/L | Standard Error 0.38 |
| IDeg OD+IAsp | Change From Baseline in Fasting Plasma Glucose (FPG) | -1.90 mmol/L | Standard Error 0.36 |
Secondary
Incidence of Treatment Emergent Adverse Events (TEAE)
A TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment
Time frame: Weeks 0-26
Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp BID | Incidence of Treatment Emergent Adverse Events (TEAE) | 330 number of events |
| IDeg OD+IAsp | Incidence of Treatment Emergent Adverse Events (TEAE) | 298 number of events |
Secondary
Number of Treatment Emergent Hypoglycaemic Episodes
According to the Novo Nordisk definition for confirmed hypoglycaemic episodes (severe hypoglycaemia and/or a measured Plasma Glucose (PG) \<3.1 mmol/L(56 mg/dL))
Time frame: During Weeks 0-26
Population: The safety Analysis Set (SAS): included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | 706 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | 841 episodes |
Secondary
Number of Treatment Emergent Hypoglycaemic Episodes
According to the American Diabetes Association (ADA) definition following are the categories of hypoglycaemic episodes: Severe hypoglycaemia, Documented symptomatic hypoglycaemia, Asymptomatic hypoglycaemia, Probable symptomatic hypoglycaemia and Relative hypoglycaemia
Time frame: During Weeks 0-26
Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | ADA (American Diabetes Association) | 2894 episodes |
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | Severe | 29 episodes |
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | Documented symptomatic | 1818 episodes |
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | Asymptomatic | 930 episodes |
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | Probable symptomatic | 26 episodes |
| IDegAsp BID | Number of Treatment Emergent Hypoglycaemic Episodes | Relative | 91 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | Probable symptomatic | 33 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | ADA (American Diabetes Association) | 2685 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | Asymptomatic | 728 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | Severe | 15 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | Relative | 66 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Hypoglycaemic Episodes | Documented symptomatic | 1843 episodes |
Secondary
Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes
Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Time frame: Weeks 0-26
Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp BID | Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes | 75 episodes |
| IDeg OD+IAsp | Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes | 96 episodes |