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 | 20.1 |
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 compare long-term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine (IGlar) in insulin naïve subjects with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OAD[s]). |
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E.2.2 | Secondary objectives of the trial |
To compare long-term efficacy and safety of IDegLira versus IGlar in insulin naïve subjects with T2DM inadequately controlled with OAD(s). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age ≥18 years at the time of signing informed consent - Subjects diagnosed with type 2 diabetes mellitus - HbA1c 7.0−11.0% (both inclusive) (53–97 mmol/mol) by central laboratory analysis - Body mass index ≥20 kg/m^2 - Insulin naïve subjects; 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) including any of the following antidiabetic drug(s)/regimens within 90 days prior to the day of screening: o Biguanides (metformin ≥1500 mg or maximum tolerated dose documented in the subject medical record) o Other OAD(s) allowed: sulphonylurea, glinides, pioglitazone, and DPP4-inhibitors (≥ half of the maximum approved dose according to local label or maximum tolerated dose as documented in subjects medical record) |
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E.4 | Principal exclusion criteria |
- Screening calcitonin ≥50 ng/L - Renal impairment estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2 as per CKD-EPI value to be defined as listed in the classification CKD-EPI using IDMS for serum creatinine measurement on the day of screening - Impaired liver function, defined as ALAT or ASAT ≥2.5 times upper limit of normal - Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma - History of pancreatitis (acute or chronic) - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening - Anticipated initiation or change in concomitant medications for more than 14 consecutive days or on a frequent basis known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from randomisation to inadequate glycaemic control and need for treatment intensification, defined as a glycosylated haemoglobin (HbA1c) of ≥ 7.0% at 2 consecutive visits from week 26, including week 26 if HbA1c was ≥ 7% at week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Will be assessed up to 104 weeks. |
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E.5.2 | Secondary end point(s) |
Key supportive secondary efficacy endpoints: 1. Time from randomisation to an HbA1c > 6.5% at 2 consecutive visits 2. Change from baseline in: o HbA1c o body weight o Fasting plasma glucose (FPG) o 9-point Self-measured plasma glucose (SMPG) profile (individual points in the profile) 3. Insulin dose 4. Responder (yes/no): o HbA1c < 7.0% o HbA1c ≤ 6.5%
Key supportive secondary safety endpoints 5. Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From week 26 2. After 26 weeks of treatment 3. After 26 weeks of treatment 4. After 26 and 104 weeks of treatment 5. During 26 and 104 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Brazil |
European Union |
India |
Israel |
Mexico |
Norway |
Russian Federation |
South Africa |
Turkey |
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 | 8 |
E.8.9.1 | In the Member State concerned days | 23 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 23 |