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 | 18.0 |
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 the efficacy of insulin degludec/liraglutide (IDegLira), using a once weekly titration algorithm, in controlling glycaemia in insulin-naïve subjects with type 2 diabetes mellitus (T2DM), inadequately controlled on metformin alone or in combination with pioglitazone. This is done by comparing the difference in change from baseline HbA1c (glycosylated haemoglobin) after 32 weeks of treatment to a non-inferiority limit of 0.30 % for once weekly titration vs. twice weekly titration. |
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E.2.2 | Secondary objectives of the trial |
To compare efficacy in terms of other measures of glycaemic control and safety of IDegLira titrated using a once weekly vs. twice weekly algorithm after 32 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Type 2 diabetes mellitus
2. Male or female ≥18 years of age
3. HbA1c 7.0 - 10.0% [53 mmol/mol - 86 mmol/mol] (both inclusive), confirmed by the central laboratory
4. Stable daily treatment with metformin (≥1500 mg or max tolerated dose) ± pioglitazone (≥30 mg) for at least 90 days prior to screening
5. Body Mass Index (BMI) ≤40 kg/m^2 |
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E.4 | Principal exclusion criteria |
1. Current use of any anti-diabetic drugs (except for metformin and pioglitazone) or anticipated change in concomitant medication, which, in the opinion of the investigator, could interfere with the glucose metabolism (e.g. systemic corticosteroids)
2. Previous and / or current treatment with insulin (short term treatment due to intercurrent illness, including gestational diabetes, is allowed at the discretion of the investigator)
3. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, sulpfonylurea, glinides, dipeptidyl peptidase 4 (DPP-4) inhibitors or sodium-glucose co-transporter 2 (SGLT2) inhibitors within 90 days prior to the screening visit
4. Impaired liver function, defined as alanine aminotransferase (ALAT) ≥2.5 times upper normal range (UNR)
5. Impaired renal function defined as serum-creatinine ≥133 μmol/L ( ≥1.5 mg/dL) for males and ≥125 μmol/L ( ≥1.4 mg/dL) for females, or as defined according to local contraindications for metformin
6. Screening calcitonin ≥50 ng/L
7. Proliferative retinopathy or maculopathy (macular oedema) requiring acute treatment, according to investigator's clinical judgment
8. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
9. History of pancreatitis (acute or chronic) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 32 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Responder (Yes/No) for:
– HbA1c <7.0%
– HbA1c ≤6.5% |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 32 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Comparison of two different titration algorithms |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Canada |
European Union |
Russian Federation |
Serbia |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 6 |