E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 demonstrate the effect on glycaemic control of once weekly insulin icodec in combination with insulin aspart, with or without non-insulin anti-diabetic drugs, in subjects with type 2 diabetes (T2D) on a basal-bolus regimen. This includes comparing the difference in change from baseline in glycosylated haemoglobin (HbA1c) between insulin icodec and insulin glargine after 26 weeks of treatment to a non-inferiority limit of 0.3%. |
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E.2.2 | Secondary objectives of the trial |
To compare safety with once weekly insulin icodec versus once daily insulin glargine, both in combination with insulin aspart, with or without non-insulin anti-diabetic drugs, in subjects with T2D on a basal-bolus regimen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female aged above or equal to 18 years at the time of signing informed consent. - Diagnosed with T2D 180 days or more prior to the day of screening. - HbA1c from 7.0-10.0% (53.0-85.8 mmol/mol) both inclusive at screening confirmed by central laboratory analysis. - Treated with once daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) and 2-4 daily injections of bolus insulin analog (insulin aspart, faster acting insulin aspart, insulin lispro, insulin glulisine) 90 days or more prior to the day of screening with or without any of the following anti-diabetic drugs/regimens with stable doses 90 days or more prior to screening: -Metformin -Sulfonylureas -Meglitinides (glinides) -Dipeptidyl peptidase-4 (DPP-4) inhibitors -Sodium-glucose Cotransporter-2 (SGLT2) inhibitors -Thiazolidinediones -Alpha-glucosidase inhibitors -Oral combination products (for the allowed individual oral anti-diabetic drugs) -Oral or injectable glucagon-like peptide-1 (GLP-1) receptor agonists - Body mass index (BMI) equal to or below 40.0 kg/m^2 . |
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E.4 | Principal exclusion criteria |
- Any episodes (as declared by the subject or in the medical records) of diabetic ketoacidosis within 90 days prior to the day of screening. - Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening. - Chronic heart failure classified as being in New York Heart Association Class IV at screening. - Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids). - Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline week 0 (V2) to week 26 (V28) |
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E.5.2 | Secondary end point(s) |
1. Change in fasting plasma glucose (FPG) 2. Time in target-range 3.9–10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 3. Number of severe hypoglycaemic episodes (level 3) 4. Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by blood glucose (BG) meter) 5. Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) 6. Time spent below 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 7. Time spent above 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 8. Mean weekly insulin dose 9. Change in body weight |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline week 0 (V2) to week 26 (V28) 2. From week 22 (V24) to week 26 (V28) 3.-5. From baseline week 0 (V2) to week 31 (V30) 6.-7. From week 22 (V24) to week 26 (V28) 8. From week 24 (V26) to week 26 (V28) 9. From baseline week 0 (V2) to week 26 (V28) |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
India |
Japan |
Mexico |
Russian Federation |
United States |
European Union |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 6 |