Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted globally. The aim of the trial is to compare sequential addition of insulin aspart versus further dose increase with insulin degludec/liraglutide in subjects with type 2 diabetes mellitus, previously treated with insulin degludec/liraglutide and metformin and in need of further intensification. This is an extension to trial NN9068-3952, NCT01952145 (DUAL™ V).
Interventions
DRUGinsulin degludec/liraglutide
Insulin degludec/liraglutide will be given subcutaneously (s.c., under the skin) once daily in combination with metformin. Dose individually adjusted.
DRUGinsulin aspart
Dose titration of insulin aspart will be based on the respective pre-meal(s) and bedtime SMPG measured daily.
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
* Completion (Visit 28) of NN9068-3952 with insulin degludec/liraglutide + metformin * HbA1c (glycosylated haemoglobin) above or equal to 7 percent at Visit 27 of NN9068-3952 trial
Exclusion criteria
* Clinically significant diseases of the major organ systems * Screening calcitonin above or equal to 50 ng/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) | Week 0, week 26 | Change from baseline in HbA1c after 26 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight | Week 0, week 26 | Change from baseline in body weight after 26 weeks of treatment. |
| Number of Treatment-emergent Confirmed Hypoglycaemic Episodes | Week 0 - 26 | Treatment-emergent hypoglycaemic episodes: if the onset of the episode occurred on or after the first day of investigational medicinal product administration, and no later than 7 days after the last day on investigational medicinal product. Confirmed hypoglycaemia: subject unable to treat himself/herself and/or have a recorded plasma glucose \< 3.1 mmol/L (56 mg/dL). |
Countries
Argentina, Australia, Greece, Hungary, Mexico, Russia, Slovakia, South Africa, Spain, United States
Participant flow
Recruitment details
The trial was conducted at 19 sites in 8 countries as follows: Argentina: 2 sites; Greece: 2 sites, Hungary: 1 site; Russian Federation: 5 sites; Slovakia: 4 sites, South Africa: 1 site; Spain: 1 site, United States: 3 sites.
Pre-assignment details
Subjects with type 2 diabetes mellitus who were inadequately controlled (HbA1c level ≥ 7% \[53 mmol/mol\]) on treatment with IDegLira and metformin after 26 weeks of treatment in the NN9068-3952 trial were screened. Eligible subjects were randomised in a 1:1 manner to one of the two parallel treatment groups (IDegLira or IDegLira + IAsp).
Participants by arm
| Arm | Count |
|---|---|
| IDegLira Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose). | 16 |
| IDegLira + IAsp IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose). | 15 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unclassified | 1 | 2 |
| Overall Study | Withdrawal criteria | 1 | 0 |
Baseline characteristics
| Characteristic | IDegLira | IDegLira + IAsp | Total |
|---|---|---|---|
| Age, Continuous | 57.3 Years STANDARD_DEVIATION 11.7 | 57.4 Years STANDARD_DEVIATION 11.2 | 57.4 Years STANDARD_DEVIATION 11.3 |
| Gender Female | 9 Participants | 8 Participants | 17 Participants |
| Gender Male | 7 Participants | 7 Participants | 14 Participants |
| HbA1c | 7.6 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 7.7 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 | 7.6 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 16 | 3 / 15 |
| serious Total, serious adverse events | 1 / 16 | 2 / 15 |
Outcome results
Primary
Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Change from baseline in HbA1c after 26 weeks of treatment.
Time frame: Week 0, week 26
Population: Full analysis set (FAS) included all randomised subjects (31 subjects). Missing data were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegLira | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -0.43 Percentage of glycosylated haemoglobin | Standard Deviation 0.94 |
| IDegLira + IAsp | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -0.14 Percentage of glycosylated haemoglobin | Standard Deviation 1.09 |
Comparison: The response and change from baseline in the response after 26 weeks of treatment was analysed using an analysis of covariance (ANCOVA) method with treatment and baseline IDegLira dose strata as fixed factors and baseline response as a covariate. Missing data were imputed using LOCF.p-value: 0.42795% CI: [-1.05, 0.46]ANCOVA
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight after 26 weeks of treatment.
Time frame: Week 0, week 26
Population: FAS included all randomised subject (31 subjects). Missing data were imputed using the LOCF method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegLira | Change From Baseline in Body Weight | 0.9 Kilograms | Standard Deviation 2.1 |
| IDegLira + IAsp | Change From Baseline in Body Weight | 1.5 Kilograms | Standard Deviation 3.2 |
Secondary
Number of Treatment-emergent Confirmed Hypoglycaemic Episodes
Treatment-emergent hypoglycaemic episodes: if the onset of the episode occurred on or after the first day of investigational medicinal product administration, and no later than 7 days after the last day on investigational medicinal product. Confirmed hypoglycaemia: subject unable to treat himself/herself and/or have a recorded plasma glucose \< 3.1 mmol/L (56 mg/dL).
Time frame: Week 0 - 26
Population: Safety analysis set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (31 subjects). Confirmed hypoglycaemic episodes were reported by 2 subjects in IDegLira arm and 2 subjects in IDegLira + IAsp arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegLira | Number of Treatment-emergent Confirmed Hypoglycaemic Episodes | 34 Number of episodes |
| IDegLira + IAsp | Number of Treatment-emergent Confirmed Hypoglycaemic Episodes | 4 Number of episodes |