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 non-insulin anti-diabetic drugs, in insulin naïve subjects with type 2 diabetes (T2D). This includes comparing the difference in change from baseline in glycosylated haemoglobin (HbA1c) between insulin icodec and insulin glargine after 52 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 parameters of glycaemic control and safety of once weekly insulin icodec with once daily insulin glargine, both in combination with non-insulin anti-diabetic drugs, in insulin naïve subjects with T2D. |
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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 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis. - Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes. - Stable daily dose(s) 90 days or more prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s): a. Any metformin formulations equal to or above 1500 mg or maximum tolerated or effective dose. b. Any metformin combination formulations equal to or above 1500 mg or maximum tolerated or effective dose. c. Any of the following oral anti-diabetic drug classes including combinations (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose). - Sulfonylureas - Meglitinides (glinides) - Dipeptidyl peptidase 4 (DPP-4) inhibitors - Sodium-glucose Cotransporter-2 (SGLT2) inhibitors - Thiazolidinedione - Alpha-glucosidase inhibitor - Oral combination products (for the allowed individual Oral Anti-diabetic Drugs (OADs)) - 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 (NYHA) 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 52 (V46) |
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E.5.2 | Secondary end point(s) |
1. Time in target range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 2. Change in fasting plasma glucose (FPG) 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 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. Number of severe hypoglycaemic episodes (level 3) 7. Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL) confirmed by BG meter) 8. 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) 9. Mean weekly insulin dose 10. Change in body weight 11. Time spent below 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 12. Time spent below 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From week 48 (V42) to week 52 (V46) 2.-5. From baseline week 0 (V2) to week 52 (V46) 6.-8. From baseline week 0 (V2) to week 83 (V63) 9. From week 50 (V44) to week 52 (V46) 10. From baseline week 0 (V2) to week 52 (V46) 11.-12. From week 48 (V42) to week 52 (V46) |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Mexico |
European Union |
India |
Israel |
Japan |
Russian Federation |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 5 |