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 confirm non-inferiority of once weekly IcoSema compared with daily insulin glargine combined with insulin aspart, both treatment arms with or without OADs, in terms of glycaemic control measured by change in HbA1c from baseline after 52 weeks in participants with T2D inadequately controlled with daily basal insulin using a non-inferiority margin of 0.3%-point. |
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E.2.2 | Secondary objectives of the trial |
- To confirm superiority of once weekly IcoSema compared to daily insulin glargine combined with insulin aspart, both treatment arms with or without OADs, in participants with T2D inadequately controlled with daily basal insulin in terms of: • Change in body weight from baseline after 52 weeks • Number of clinically significant hypoglycaemic (level 2) or severe hypoglycaemic (level 3) episodes during 52 weeks and the 5 week follow up period • Weekly insulin dose (total) from week 50 to week 52
- To compare parameters of glycaemic control, patient reported outcomes and safety of once weekly IcoSema with daily insulin glargine combined with insulin aspart, both treatment arms with or without OADs, in participants with T2D inadequately controlled with daily basal insulin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female and age above or equal to 18 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus 180 days or more before screening. - HbA1c of 7.0-10.0% (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. - Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses 90 days or more before screening: * Metformin * Sulfonylureas(a) * Meglitinides (glinides)(a) * DPP-4 inhibitors(a) * Sodium-glucose co-transporter 2 inhibitors * Alpha-glucosidase-inhibitors * Thiazolidinediones * Marketed oral combination products only including the products listed above. - Body mass index (BMI) less than or equal to 40.0 kg/m^2.
(a) Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation. |
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E.4 | Principal exclusion criteria |
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method. - Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid, hormones, or systemic corticosteroids). - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. - Any episodes(a) of diabetic ketoacidosis within 90 days before screening. - Presence or history of pancreatitis (acute or chronic) within 180 days before screening. - Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening. - Chronic heart failure classified as being in New York Heart Association Class IV at screening. - Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator. - Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before 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.
(a) as declared by the participant or in the medical records. |
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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 (V54) |
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E.5.2 | Secondary end point(s) |
1. Change in body weight 2. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) (Number of episodes) 3. Weekly insulin dose (total) 4. Time in range 3.9 10.0 mmol/L (70-180 mg/dL)* 5. Time spent < 3.0 mmol/L (54 mg/dL)* 6. Time spent > 10.0 mmol/L (180 mg/dL)* 7. Change in fasting plasma glucose (FPG) 8. Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction 9. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) 10. Number of severe hypoglycaemic episodes (level 3)
* 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 baseline week 0 (V2) to week 52 (V54) 2. From baseline week 0 (V2) to week 57 (V56) 3. From week 50 (V52) to week 52 (V54) 4.-6. From week 48 (V50) to week 52 (V54) 7.-8. From baseline week 0 (V2) to week 52 (V54) 9.-10. From baseline week 0 (V2) to week 57 (V56) |
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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
| Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Malaysia |
South Africa |
Thailand |
United States |
European Union |
Turkey |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 17 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 17 |