E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 1 |
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E.1.1.1 | Medical condition in easily understood language |
Diabetes Mellitus, Type 1 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To confirm the efficacy of insulin degludec administered once daily plus mealtime insulin aspart in controlling glycaemia with respect to change from baseline in glycosylated haemoglobin (HBA1c) after 26 weeks of treatment. This is done by comparing the difference in change in HbA1c between insulin degludec + insulin aspart and insulin detemir + insulin aspart to a non-inferiority limit of 0.4%, and if non-inferiority is confirmed, to a superiority limit of 0%. |
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E.2.2 | Secondary objectives of the trial |
▪ To compare the efficacy and safety between the two treatment arms
▪ To investigate the pharmacokinetics of insulin degludec and insulin detemir in different age groups using a sparse sampling approach and population pharmacokinetic (PK) modelling. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Informed consent, and child assent as age-appropriate, obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject). The parents or legal representative of the child must sign and date the Informed Consent Form according to local requirements. The child, if possible, parents or legal representative of the child must sign and date the Child Assent Form according to local requirements.
2) Male or female diagnosed with type 1 diabetes mellitus (T1DM) (based on clinical judgement and supported by laboratory analysis as per local guidelines).
3) Age: 1 to less than 18 years of age at randomisation
4) Ongoing daily treatment with insulin (any regimen) for at least 3 months prior to Visit 1. No OADs are allowed.
5) HbA1c ≤ 11% |
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E.4 | Principal exclusion criteria |
1) Known or suspected hypersensitivity to trial product(s) or related products
2) Previous participation in this trial. Participation is defined as randomisation
3) Girls who are pregnant, breastfeeding or intend to become pregnant
4) Girls, who have had menarche and are not using adequate contraceptive measures according to local requirements
5) Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the Investigator
6) More than 1 diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to
Visit 1
7) Significant concomitant disease, except for conditions associated with type 1 diabetes mellitus, which in the Investigator’s opinion could interfere with the trial
8) The receipt of any investigational drug within 1 month prior to Visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c (%) (analysed by central laboratory) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in HbA1c (%) (analysed by central laboratory)
2. Change from baseline in fasting blood glucose (FPG) (analysed by central laboratory)
3. Number of treatment emergent adverse events (TEAEs)
4. Number of hypoglycaemic episodes (severe episodes or episodes with plasma glucose (PG) ≤ 3.9 mmol/L (70 mg/dL) with or without symptoms of hypoglycaemia) during the trial; nocturnal [11 p.m. - 7 a.m./23:00 – 07:00] and over the entire day (24 hours)
5. Number of self-measured hyperglycaemia (episodes of PG > 11.1 mmol/L (200 mg/dL))
6. Number of episodes with self monitored blood ketones >1.5 mmol (capillary blood ketone measurement to be performed if self-measured plasma glucose (SMPG) exceeds 14.0 mmol/l (250 mg/dL))
7. Steady-state plasma concentrations of insulin degludec and insulin detemir on three different visits (three different weeks)
8. Insulin antibodies (insulin degludec specific, insulin detemir specific, insulin aspart specific and antibodies cross-reacting to human insulin). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 52 weeks of treatment
2. After 26 weeks and 52 weeks of treatment
3. After 26 weeks and 52 weeks of treatment
4. After 26 weeks and 52 weeks of treatment
5. After 26 weeks and 52 weeks of treatment
6. After 26 weeks and 52 weeks of treatment
7. During the first 26 weeks of treatment
8. After 26 weeks and 52 weeks of treatment.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Finland |
France |
Germany |
Italy |
Japan |
Macedonia, the former Yugoslav Republic of |
Netherlands |
Russian Federation |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 15 |