E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 18.1 |
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 |
|
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 effect of insulin degludec/liraglutide (IDegLira) in terms of glycaemic control in subjects with type 2 diabetes mellitus (T2DM) on previous treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) ± oral anti-diabetic drug (OAD) therapy. This is done by comparing the difference in change from baseline in HbA1c after 26 weeks to a non-inferiority margin of 0.3% for IDegLira versus insulin glargine (IGlar), both in combination with SGLT2i ± OAD. |
|
E.2.2 | Secondary objectives of the trial |
To confirm superiority of IDegLira versus IGlar after 26 weeks in subjects with T2DM on previous treatment with SGLT2i ± OAD therapy in terms of one or more of the following:
1. Weight change
2. Treatment-emergent hypoglycaemic episodes (severe or blood glucose [BG] confirmed symptomatic)
3. Glycaemic control
4. Insulin dose
To compare the effect and safety of IDegLira versus IGlar after 26 weeks
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, age ≥ 18 years at the time of signing informed consent
2. Subjects diagnosed (clinically) with type 2 diabetes mellitus
3. HbA1c 7.0-11.0% [53-97 mmol/mol] (both inclusive) by central laboratory analysis
4. Body mass index (BMI) ≥ 20 kg/m^2 and < 40 kg/m^2
5. Insulin naïve subjects; however short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as well as prior insulin treatment for gestational diabetes
6. A stable daily dose for at least 90 days prior to the day of screening of any SGLT2i in monotherapy or in combination with metformin ± DPP4i ± pioglitazone. Use of pioglitazone is not allowed in subjects treated with dapagliflozin
|
|
E.4 | Principal exclusion criteria |
1. Receipt of any investigational medicinal product within 90 days prior to screening
2. Use of any OADs (other than SGLT2i in monotherapy or in combination with metformin or DPP4i or pioglitazone as described in the inclusion criteria) within 90 days prior to the day of screening
3. Use of glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., exenatide or liraglutide) within 90 days prior to the day of screening
4. Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g., diabetes ketoacidosis) in the previous 90 days prior to the day of the screening
5. Subjects presently classified as being in NYHA Class III or IV
6. Renal impairment estimated Glomerular Filtration Rate < 60 mL/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
7. Impaired liver function, defined as ALT ≥ 2.5 times upper normal limit at screening
8. Known or suspected hypersensitivity to trial product(s) or related products
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline in body weight
2. Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes
3. Insulin dose, total daily dose (U)
4. Responder (Yes/No) for HbA1c < 7.0%
5. Change from baseline in fasting plasma glucose (FPG)
6. Number of treatment-emergent adverse events
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 26 weeks
2. During 26 weeks
3. After 26 weeks
4. After 26 weeks
5. After 26 weeks
6. During 26 weeks |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
To confirm superiority of trial drug |
|
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 |
|
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 | 38 |
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 |
Argentina |
Canada |
European Union |
India |
Switzerland |
United States |
|
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
|
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |