Diabetes, Diabetes Mellitus, Type 1
Conditions
Brief summary
This trial is conducted in Europe. The aim of this research is to compare the efficacy and safety of treatment with NPH insulin and insulin detemir. You will be treated with either insulin detemir or NPH insulin once or twice daily as basal insulin. Additionally you will receive insulin aspart as bolus insulin
Interventions
DRUGinsulin NPH
s.c. injection, once or twice daily.
DRUGinsulin aspart
s.c. injection, at main meals.
DRUGinsulin detemir
s.c. injection, once or twice daily.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Insulin detemir naive * Type 1 diabetes for at least 12 months * HbA1c lesser than or equal to 11.0%
Exclusion criteria
* Significant concomitant diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycosylated Haemoglobin A1c (HbA1c) | after 52 weeks of treatment | Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Adverse Events | from week -2 to week 52 | Number of subjects reporting adverse events during the trial (from week -2 to week 52). For details, please refer to the adverse events section. |
| Observed Insulin Antibody Values | at 0 and 52 weeks | Observed insulin antibody values for insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/insulin aspart cross-reacting antibodies. |
Countries
Bulgaria, Czechia, Denmark, Finland, France, Hungary, North Macedonia, Poland, Russia, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
A total of 35 centres in 11 countries.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Detemir Individually adjusted insulin detemir dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | 177 |
| NPH Insulin Individually adjusted NPH insulin dose injected subcutaneously once daily (evening) or twice daily (morning and evening) + insulin aspart with larger meals | 170 |
| Total | 347 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Personal reasons for withdrawal | 8 | 7 |
| Overall Study | Protocol Violation | 3 | 1 |
Baseline characteristics
| Characteristic | Insulin Detemir | NPH Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 177 Participants | 170 Participants | 347 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.0 years STANDARD_DEVIATION 4.09 | 9.8 years STANDARD_DEVIATION 3.9 | 9.9 years STANDARD_DEVIATION 3.99 |
| Sex: Female, Male Female | 94 Participants | 73 Participants | 167 Participants |
| Sex: Female, Male Male | 83 Participants | 97 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 131 / 177 | 134 / 170 |
| serious Total, serious adverse events | 14 / 177 | 20 / 170 |
Outcome results
Primary
Glycosylated Haemoglobin A1c (HbA1c)
Glycosylated haemoglobin A1c (HbA1c) measured after 52 weeks of treatment and analysed by central laboratory.
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) is defined as all randomised subjects exposed to at least one dose of trial product with a postbaseline observation, classified according to randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Detemir | Glycosylated Haemoglobin A1c (HbA1c) | 8.75 Percent (%) glycosylated haemoglobin | Standard Error 0.11 |
| NPH Insulin | Glycosylated Haemoglobin A1c (HbA1c) | 8.64 Percent (%) glycosylated haemoglobin | Standard Error 0.11 |
95% CI: [-0.12, 0.36]ANCOVA
Secondary
Number of Subjects Reporting Adverse Events
Number of subjects reporting adverse events during the trial (from week -2 to week 52). For details, please refer to the adverse events section.
Time frame: from week -2 to week 52
Population: Safety analysis set (SAS): all randomised subjects exposed to at least one dose of trial product, classified according to actual treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Detemir | Number of Subjects Reporting Adverse Events | 132 participants |
| NPH Insulin | Number of Subjects Reporting Adverse Events | 135 participants |
Secondary
Observed Insulin Antibody Values
Observed insulin antibody values for insulin detemir specific antibodies, insulin aspart specific antibodies and insulin detemir/insulin aspart cross-reacting antibodies.
Time frame: at 0 and 52 weeks
Population: Safety analysis set (SAS): All randomised subjects exposed to at least one dose of trial product, classified according to actual treatment. In some cases, antibody samples were taken earlier than required. These results were not included. A shipment of antibody samples was lost during transportation, and thus these antibody data were missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir | Observed Insulin Antibody Values | Insulin detemir specific, week 0 (n=127, 112) | 3.23 Percent bound of total | Standard Deviation 1.03 |
| Insulin Detemir | Observed Insulin Antibody Values | Insulin detemir specific, week 52 (n=125, 128) | 5.15 Percent bound of total | Standard Deviation 3.3 |
| Insulin Detemir | Observed Insulin Antibody Values | Cross-reacting insulin, week 0 (n=130, 113) | 27.06 Percent bound of total | Standard Deviation 19.1 |
| Insulin Detemir | Observed Insulin Antibody Values | Cross-reacting insulin, week 52 (n=132, 135) | 43.70 Percent bound of total | Standard Deviation 15.6 |
| Insulin Detemir | Observed Insulin Antibody Values | Insulin aspart specific, week 0 (n=126, 111) | 2.26 Percent bound of total | Standard Deviation 2.32 |
| Insulin Detemir | Observed Insulin Antibody Values | Insulin aspart specific, week 52 (n=128, 133) | 4.20 Percent bound of total | Standard Deviation 4.35 |
| NPH Insulin | Observed Insulin Antibody Values | Insulin aspart specific, week 0 (n=126, 111) | 2.24 Percent bound of total | Standard Deviation 2.99 |
| NPH Insulin | Observed Insulin Antibody Values | Insulin detemir specific, week 0 (n=127, 112) | 2.95 Percent bound of total | Standard Deviation 1.23 |
| NPH Insulin | Observed Insulin Antibody Values | Cross-reacting insulin, week 52 (n=132, 135) | 30.19 Percent bound of total | Standard Deviation 17.3 |
| NPH Insulin | Observed Insulin Antibody Values | Insulin detemir specific, week 52 (n=125, 128) | 3.01 Percent bound of total | Standard Deviation 1.66 |
| NPH Insulin | Observed Insulin Antibody Values | Insulin aspart specific, week 52 (n=128, 133) | 2.68 Percent bound of total | Standard Deviation 3.6 |
| NPH Insulin | Observed Insulin Antibody Values | Cross-reacting insulin, week 0 (n=130, 113) | 27.26 Percent bound of total | Standard Deviation 18.6 |