Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to compare the efficacy and safety of NN1250 (insulin degludec (IDeg)) once daily in insulin naïve subjects with type 2 diabetes mellitus when titrated using two different self-titration algorithms (dose individually adjusted) in combination with metformin.
Interventions
DRUGinsulin degludec
Injected subcutaneously (under the skin) once daily. Dose 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
* Type 2 diabetes (diagnosed clinically) for at least 24 weeks prior to randomisation (Visit 2) * Current treatment: metformin monotherapy or metformin in any combination with 1 or 2 other OADs including an insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPP-IV) inhibitors, alpha-glucosidase inhibitors, thiazolidinediones (TZDs) all with unchanged dosing for at least 12 weeks prior to randomisation (Visit 2)-metformin: alone or in combination (including fixed combination) must be at least 1000 mg daily * HbA1c 7.0-10.0% (both inclusive) by central laboratory analysis * BMI (Body Mass Index) no higher than 45.0 kg/m\^2
Exclusion criteria
* Treatment with glucagon-like peptide 1 (GLP-1) receptor agonist within the last 12 weeks prior to Visit 2 * Suffer from a life threatening disease (e.g. cancer) * Females of childbearing potential who are pregnant (as determined by central laboratory beta-human chorionic gonadotropin (beta-hCG), breast feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive methods as required by law or practise \[for Germany, adequate contraceptive methods are: implants, injectables, combined oral contraceptives, hormonal IUD, sexual abstinence or vasectomised partner\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | Week 0, Week 26 | Change from baseline in HbA1c after 26 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) | Week 0, Week 26 | Change from baseline in FPG after 26 weeks of treatment. |
| Rate of Treatment Emergent Adverse Events (AEs) | Week 0 to Week 26 + 7 days follow up | Corresponds to rate of AEs per 100 patient years of exposure. 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. |
| Rate of Confirmed Hypoglycaemic Episodes | Week 0 to Week 26 + 7 days follow up | Observed 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. |
| Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Week 0 to Week 26 + 7 days follow up | Observed rate of nocturnal 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 occurring between 00:01 and 05:59 a.m. |
Countries
Finland, Germany, Spain, United States
Participant flow
Recruitment details
The trial was conducted at 43 sites in 4 countries: Finland (5), Germany (6), Spain (6) and United States of America (26).
Pre-assignment details
Subjects continued on metformin treatment at the pre-randomisation dose level and dosing frequency.
Participants by arm
| Arm | Count |
|---|---|
| IDeg Simple Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration. | 111 |
| IDeg Step Wise Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration. | 111 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Withdrawal Criteria | 5 | 7 |
Baseline characteristics
| Characteristic | IDeg Simple | IDeg Step Wise | Total |
|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 9.5 | 58.5 years STANDARD_DEVIATION 11.1 | 58.9 years STANDARD_DEVIATION 10.3 |
| Fasting plasma glucose (FPG) | 9.3 mmol/L STANDARD_DEVIATION 2.6 | 9.4 mmol/L STANDARD_DEVIATION 2.8 | 9.4 mmol/L STANDARD_DEVIATION 2.7 |
| Glycosylated haemoglobin (HbA1c) | 8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 43 Participants | 36 Participants | 79 Participants |
| Sex: Female, Male Male | 68 Participants | 75 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 110 | 14 / 111 |
| serious Total, serious adverse events | 5 / 110 | 7 / 111 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
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 was imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg Simple | Change in Glycosylated Haemoglobin (HbA1c) | -1.09 percentage of glycosylated haemoglobin | Standard Deviation 1.05 |
| IDeg Step Wise | Change in Glycosylated Haemoglobin (HbA1c) | -0.93 percentage of glycosylated haemoglobin | Standard Deviation 0.97 |
Secondary
Change in Fasting Plasma Glucose (FPG)
Change from baseline in FPG after 26 weeks of treatment.
Time frame: Week 0, Week 26
Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). For 7 subjects baseline values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg Simple | Change in Fasting Plasma Glucose (FPG) | -3.27 mmol/L | Standard Deviation 3.56 |
| IDeg Step Wise | Change in Fasting Plasma Glucose (FPG) | -2.68 mmol/L | Standard Deviation 3.5 |
Secondary
Rate of Confirmed Hypoglycaemic Episodes
Observed 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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg Simple | Rate of Confirmed Hypoglycaemic Episodes | 160 Episodes/100 years of patient exposure |
| IDeg Step Wise | Rate of Confirmed Hypoglycaemic Episodes | 117 Episodes/100 years of patient exposure |
Secondary
Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Observed rate of nocturnal 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 occurring 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg Simple | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 21 Episodes/100 years of patient exposure |
| IDeg Step Wise | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 10 Episodes/100 years of patient exposure |
Secondary
Rate of Treatment Emergent Adverse Events (AEs)
Corresponds to rate of AEs per 100 patient years of exposure. 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 26 + 7 days follow up
Population: The safety analysis set included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IDeg Simple | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 346 Events/100 years of patient exposure |
| IDeg Simple | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 15 Events/100 years of patient exposure |
| IDeg Simple | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 15 Events/100 years of patient exposure |
| IDeg Simple | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 69 Events/100 years of patient exposure |
| IDeg Simple | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 262 Events/100 years of patient exposure |
| IDeg Simple | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs | 0 Events/100 years of patient exposure |
| IDeg Step Wise | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 291 Events/100 years of patient exposure |
| IDeg Step Wise | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 379 Events/100 years of patient exposure |
| IDeg Step Wise | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 79 Events/100 years of patient exposure |
| IDeg Step Wise | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 15 Events/100 years of patient exposure |
| IDeg Step Wise | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs | 2 Events/100 years of patient exposure |
| IDeg Step Wise | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 10 Events/100 years of patient exposure |