E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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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 glycaemic control, measured as HbA1c, of insulin detemir given once daily in combination with sitagliptin and metformin versus sitagliptin and metformin ± SU after a 26-week treatment period in subjects with type 2 diabetes inadequately controlled on metformin treatment with or without other OADs. |
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E.2.2 | Secondary objectives of the trial |
To assess and compare efficacy and safety of insulin detemir given once daily in combination with sitagliptin and metformin versus sitagliptin and metformin ± SU after a 26-week treatment period in terms of: • Proportion of subjects achieving: - HbA1c ≤ 7.0% or 6.5% - HbA1c ≤ 7.0% or 6.5% without symptomatic hypoglycaemia with a plasma glucose value < 4.0 mmol/L (< 72 mg/dL) or any single plasma glucose value < 3.1 mmol/L (56 mg/dL) in the last three months of treatment • The glycaemic control as measured by: - FPG (central laboratory values) -9-point plasma glucose profiles (self-measured) • Incidence of hypoglycaemic episodes during the trial: nocturnal (23:00-05:59) and over 24 hours • Incidence of adverse events (AEs) • Change in: - clinical and laboratory safety parameters - body weight - waist:hip circumference ratio |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Informed consent obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject) 2. Male or female, age ≥ 18 years 3. Diagnosed with type 2 diabetes for a minimum of 6 months prior to Visit 1 4. Treatment with at least 1000 mg metformin per day for at least 3 months prior to Visit 1 5. Subject is insulin-naïve (short-term insulin treatment of up to 14 days is allowed) 6. Subject is DPP-4 inhibitor-naïve 7. HbA_1c 7.5-10.0 % (both inclusive) by central laboratory analysis 8. Body Mass Index (BMI) ≤ 45.0 kg/m^2 9. Able and willing to administer subcutaneous injections every day 10. Able and willing to perform mandatory SMPG measurements |
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E.4 | Principal exclusion criteria |
1. Any contraindication to insulin detemir or sitagliptin according to the local labelling 2. Known or suspected allergy or intolerance to any of the trial products or related products 3. Previous participation in this trial (participation is defined as randomised) 4. Treatment with thiazolidinedione (TZD) or GLP-1 analogues within 2 months prior to Visit 1 5. Cardiac disease, within the last 12 months prior to Visit 1, defined as: decompensated heart failure New York Heart Association (NYHA) class III or IV; unstable angina pectoris; or myocardial infarction 6. Severe hypertension, systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 100 mm Hg, after 5 minutes rest in the sitting position 7. Anticipated change of dose of any systemic treatment with products, which in the Investigator’s opinion could interfere with glucose metabolism (e.g. systemic corticosteroids) 8. Clinically significant diseases (except for conditions associated with type 2 diabetes) which, in the Investigator’s opinion may confound the results of the trial or pose additional risk in administering trial product(s) 9. Impaired hepatic function as indicated by aspartate aminotransferase (ASAT/SGOT) or alanine aminotransferase (ALAT/SGPT) > 2.5 times the upper normal range (one re-test within one week is permitted. Last sample will be conclusive.) 10. Impaired renal function as indicated by serum creatinine levels ≥ 126 µmol/L (1.43 mg/dL) for males or ≥ 111 µmol/L (1.26 mg/dL) for females or glomerular filtration rate below 60 mL/min, calculated by the Cockroft & Gault formula and according to local practise for metformin use (one re-test within a week is permitted. Last sample will be conclusive.) 11. Proliferative retinopathy or macular oedema requiring acute treatment 12. Female of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) 13. Anticipated lifestyle changes (eating, exercise, sleeping pattern) during the study, e.g. shiftwork 14. Mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding or co-operation, including subjects not able to read or write 15. Any conditions that the Investigator judges would interfere with trial participation or evaluation of the results 16. Known or suspected abuse of alcohol, narcotics or illicit substances 17. The receipt of any investigational product within 4 weeks prior to Visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
HbA1c 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 | Yes |
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.8.3 |
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 | 24 |
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 | Information not present in EudraCT |
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 |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 7 |