Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in the United States of America (USA). The aim of this trial is to compare the efficacy and safety of two different formulations of insulin degludec (IDeg) in subjects with type 2 diabetes.
Interventions
DRUGinsulin degludec
Injected subcutaneously (under the skin) once daily, in combination with unchanged pre-trial oral anti-diabetic drug (OAD) treatment. 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
* Type 2 diabetes (diagnosed clinically) for minimum 24 weeks prior to randomisation (visit 2) * Current treatment with basal-only insulin (no prandial insulin) consisting of either insulin detemir once daily (OD), insulin glargine OD or neutral protamine hagedorn (NPH) insulin OD/twice daily (BID) for at least 12 weeks prior to randomisation (visit 2), in combination with stable doses of OAD(s) (metformin, insulin secretagogue (sulfonylurea or glinide), alpha-glucosidase inhibitor, pioglitazone or dipeptidyl peptidase IV (DPP-IV) inhibitor in any approved (according to label) dose or combination. Stable OAD doses are defined as unchanged doses for at least 12 weeks prior to randomisation (visit 2) * HbA1c (glycosylated haemoglobin) between 7.0-10.0% (both inclusive) by central laboratory analysis * Body mass index (BMI) below or equal to 45 kg/m\^2 * Ability and willingness to adhere to the protocol including self-measured plasma glucose (SMPG) according to the protocol
Exclusion criteria
* Treatment with rosiglitazone within the last 12 weeks prior to randomisation (visit 2) * Treatment with glucagon like peptide-1 (GLP-1) receptor agonists within the last 12 weeks prior to randomisation (visit 2) * Recurrent severe hypoglycaemia (more than one severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator (trial physician) * Previous participation in this trial. Participation is defined as randomised. Re-screening is allowed once during the recruitment period * Known or suspected hypersensitivity to trial products or related products * The receipt of any investigational drug within 4 weeks prior to randomisation (visit 2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | Week 0, Week 22 | Change from baseline in HbA1c after 22 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) | Week 0, Week 22 | Change from baseline in FPG after 22 weeks of treatment. |
| Rate of Treatment Emergent Adverse Events (AEs) | Week 0 to Week 22 + 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 22 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were 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 22 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at 44 sites within United States of America.
Pre-assignment details
Subjects who were treated with basal insulin in combination with unchanged dosing of oral antidiabetic drug treatment (e.g. metformin, pioglitazone or DPP-IV inhibitor) in any approved dose or combination at unchanged dosing for at least 12 weeks prior to randomisation in a 1:1 manner to IDeg 200 U/mL or IDeg.
Participants by arm
| Arm | Count |
|---|---|
| IDeg 200 U/mL Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day. | 186 |
| IDeg Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day. | 187 |
| Total | 373 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal Criteria | 14 | 10 |
Baseline characteristics
| Characteristic | IDeg 200 U/mL | IDeg | Total |
|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 10 | 60.3 years STANDARD_DEVIATION 10.2 | 59.8 years STANDARD_DEVIATION 10.1 |
| Fasting plasma glucose (FPG) | 8.3 mmol/L STANDARD_DEVIATION 3 | 8.3 mmol/L STANDARD_DEVIATION 3.4 | 8.3 mmol/L STANDARD_DEVIATION 3.2 |
| Glycosylated haemoglobin (HbA1c) | 8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 98 Participants | 70 Participants | 168 Participants |
| Sex: Female, Male Male | 88 Participants | 117 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 184 | 26 / 187 |
| serious Total, serious adverse events | 9 / 184 | 11 / 187 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline in HbA1c after 22 weeks of treatment
Time frame: Week 0, Week 22
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 200 U/mL | Change in Glycosylated Haemoglobin (HbA1c) | -0.79 percentage of glycosylated haemoglobin | Standard Deviation 0.89 |
| IDeg | Change in Glycosylated Haemoglobin (HbA1c) | -0.70 percentage of glycosylated haemoglobin | Standard Deviation 0.9 |
Secondary
Change in Fasting Plasma Glucose (FPG)
Change from baseline in FPG after 22 weeks of treatment.
Time frame: Week 0, Week 22
Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). For 5 subjects baseline values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 200 U/mL | Change in Fasting Plasma Glucose (FPG) | -2.26 mmol/L | Standard Deviation 3.07 |
| IDeg | Change in Fasting Plasma Glucose (FPG) | -2.40 mmol/L | Standard Deviation 3.42 |
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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time frame: Week 0 to Week 22 + 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) |
|---|---|---|
| IDeg 200 U/mL | Rate of Confirmed Hypoglycaemic Episodes | 517 Episodes/100 years of patient exposure |
| IDeg | Rate of Confirmed Hypoglycaemic Episodes | 566 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.
Time frame: Week 0 to Week 22 + 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) |
|---|---|---|
| IDeg 200 U/mL | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 127 Episodes/100 years of patient exposure |
| IDeg | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 170 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 22 + 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 | Group | Value (NUMBER) |
|---|---|---|---|
| IDeg 200 U/mL | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 416 Events/100 years of patient exposure |
| IDeg 200 U/mL | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 20 Events/100 years of patient exposure |
| IDeg 200 U/mL | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 27 Events/100 years of patient exposure |
| IDeg 200 U/mL | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 130 Events/100 years of patient exposure |
| IDeg 200 U/mL | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 259 Events/100 years of patient exposure |
| IDeg 200 U/mL | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs | 0 Events/100 years of patient exposure |
| IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 172 Events/100 years of patient exposure |
| IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 300 Events/100 years of patient exposure |
| IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 107 Events/100 years of patient exposure |
| IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 16 Events/100 years of patient exposure |
| IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs | 0 Events/100 years of patient exposure |
| IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 21 Events/100 years of patient exposure |