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 | 14.1 |
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 superiority of insulin degludec/liraglutide versus unchanged glucagon-like peptide-1 (GLP-1) receptor agonist therapy in controlling glycaemia in insulin naïve subjects with type 2 diabetes mellitus (T2DM) inadequately controlled on GLP-1 receptor agonist therapy in combination with metformin±pioglitazone±sulphonylurea. |
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E.2.2 | Secondary objectives of the trial |
To compare general efficacy and safety of insulin degludec/liraglutide versus unchanged GLP-1 receptor agonist therapy in insulin naïve subjects with T2DM inadequately controlled with GLP-1 receptor agonist therapy in combination with metformin±pioglitazone±sulphonylurea after 26 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects with type 2 diabetes mellitus
- Male or female ≥ 18 years of age
- HbA1c 7.0-9.0% (53-75 mmol/mol) (both inclusive)
- Treatment with daily GLP-1 receptor agonist at maximum dose according to local label (i.e. 1.8 mg OD Victoza® (liraglutide) or 10 microgram twice daily (BID) Byetta® (exenatide)) or documented maximum tolerated dose (i.e. 1.2 mg OD Victoza® (liraglutide) or 5 microgram BID Byetta® (exenatide)) in combination with a stable daily dose of metformin (> 1500 mg or documented maximum tolerated dose) ± stable daily dose of pioglitazone (≥30 mg) ±stable daily dose of sulphonylurea (≥ half of the max approved dose according to local label) ≥90 days prior to screening visit (Visit 1)
- BMI (body mass index) ≤ 40 kg/m2 |
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E.4 | Principal exclusion criteria |
- Any use of oral anti-diabetic drugs (OADs) (except for metformin, pioglitazone and sulphonylurea) ≤ 90 days prior to screening visit (Visit 1)
- Use of any drug (except metformin, pioglitazone, sulphonylurea and GLP-1 receptor agonist) which in the Investigators opinion could interfere with the blood glucose level (e.g. systemic corticosteroids)
- Treatment with any insulin regimen (short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator)
- Screening calcitonin ≥ 50 ng/l
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
- Cardiovascular disorders defined as: congestive heart failure (New York Heart Association (NYHA) class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the past 52 weeks prior to screening visit (Visit 1) and/or planned coronary, carotid or peripheral artery revascularisation procedures
- Proliferative retinopathy requiring acute treatment or maculopathy (macular oedema) according to the Investigator’s opinion
- Subjects with a clinical significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, endocrinological (except for the type 2 diabetes mellitus), neurological, genitourinary or haematological system that in the opinion of the Investigator may confound the results of the trial or pose additional risk in administering trial products
- History of chronic pancreatitis or idiopathic acute pancreatitis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycosylated haemoglobin (HbA1c) from baseline (randomisation, Visit 2) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
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E.5.2 | Secondary end point(s) |
1. Responders (Yes/No) achieving pre-defined target for HbA1c
- HbA1c < 7.0% (53 mmol/mol)
- HbA1c ≤ 6.5% (48 mmol/mol)
2. Change from baseline in body weight
3 Change from baseline in fasting plasma glucose (FPG)
4. Number of treatment emergent (confirmed) hypoglycaemic episodes
5. Number of treatment emergent adverse events (AEs)
6. Change from baseline in patient reported outcomes (PROs):
- Treatment related impact measure – diabetes (TRIM-D)
- Diabetes treatment satisfaction questionnaire (DTSQ) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 26 weeks of treatment
2., 3. After 26 weeks of treatment
4., 5. During 26 weeks of treatment
6. After 26 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 | 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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
European Union |
Australia |
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 | 7 |
E.8.9.1 | In the Member State concerned days | 4 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 4 |