E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes mellitus tipo 2 no insulino dependiente en pacientes ancianos (>/= 65 años)
Non-insulin dependent type 2 diabetes mellitus in elderly patients (>/= 65 years) |
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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 | 10029505 |
E.1.2 | Term | Non-insulin-dependent 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 |
The primary objective of this study will be to show the superiority of saxagliptin compared to glimepiride in bringing elderly patients (>/=65 years) with type 2 diabetes to HbA1c target <7% without hypoglycaemia (confirmed or severe) over a 52-week treatment period. Saxagliptin or glimepiride will be administered as an add-on therapy to a background therapy with metformin. |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of saxagliptin versus glimepiride given as add-on to a metformin therapy after 52 weeks of a double-blind treatment period by evaluation of secondary efficacy and safety endpoints described below: Key secondary (safety analysis) -Proportion of patients having experienced at least one hypoglycaemic event (confirmed or severe) over the 52-week double-blind treatment period Efficacy -Change from baseline to Week 52 in HbA1c -Proportion of patients achieving a therapeutic glycaemic response at Week 52 defined as HbA1c <7.0% or <6.5% -Change from baseline to Week 52 in fasting plasma glucose (FPG) and insulin -Change from baseline to Week 52 in beta-cell function (as measured by Homeostasis Model Assessment-beta [HOMA-beta] |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title of the screening study, version and date: Included in the main protocol
Objectives of the screening study: To find out whether a given patient is suitable for enrolment in a research study. The purpose of the research study is to determine whether a new investigational drug in addition to metformin is effective and safe in treating type 2 diabetes and if so, how it compares with a standard treatment, glimepiride (sulphonylurea) in addition to metformin |
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E.3 | Principal inclusion criteria |
1.Provision of informed consent prior to any study specific procedures. 2.Established clinical diagnosis of type 2 diabetes. 3.Men or women who are >/=65 years of age at time of consenting upon Visit 1. NB: The cohorts will be approximately 60% of the patients for age group 65 to 75 years and 40% for age-group >/=75 years. The enrolment to the cohorts will be stopped when the number of patients is reached. 4.Treatment with a stable metformin monotherapy, at any dose, for at least 8 weeks prior to Visit 1. 5.HbA1c >/=7.0% and </=9.0% |
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E.4 | Principal exclusion criteria |
1. Any clinically significant abnormality identified on physical examination, ECG or laboratory tests that would compromise patients safety or successful participation in the study as judged by the investigator. 2. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma. 3. Current use of any injectable or oral antihyperglycaemic agent excluding metformin. 4. Treatment with any additional oral or injectable antihyperglycaemic agent within 8 weeks prior to Visit 1. 5. Renal impairment as defined by a creatinine clearance <60 mL/min (using the Modification of Diet in Renal Disease [MDRD] equation), as well as patients with End Stage Renal Disease (ESRD) on haemodialysis 6. Treatment with systemic glucocorticoids other than replacement therapy. Inhaled, local injected and topical use of glucocorticoids is allowed. 7. Treatment with cytochrome P450 3A4 (CYP450 3A4) inducers and cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitors. 8. Past history of intolerance, allergy or hypersensitivity to glimepiride, other sulphonylureas or sulphonamides. 9. Past hypersensitivity reaction to a DPP-4 inhibitor. 10. Contraindications to therapy as outlined in the saxagliptin IB. 11. Contraindications to therapy as outlined in the glimepiride package insert. 12. Contraindications to therapy as outlined in the metformin package insert, including conditions leading to an increased risk of hypoxaemia and lactic acidosis. 13. History of haemoglobinopathies (sickle cell anaemia or thalassemias, sideroblastic anaemia). 14. History of alcohol abuse or illegal drug abuse within the past 12 months. 15. Involvement in the planning and conduct of the study (applies to AstraZeneca and Bristol-Myers Squibb personnel and study centre personnel). 16. Participation in a clinical study during the last 3 months prior to Visit 1. 17. Donation of blood, plasma or platelets within 3 months prior to Visit 1. 18. Important cognitive function problems. 19. Individuals who, in the opinion of the investigator, in which participation in this study may pose a significant risk to the patient and could render the patient unable to successfully complete the study. 20. Suspected or confirmed poor protocol or medication compliance as judged by the investigator. Additional exclusion criteria at Visit 2: 21. Active liver disease and/or significant abnormal liver function 22. Creatine kinase (CK) >10xULN 23. Any clinically significant abnormality identified on physical examination or laboratory tests, which in the judgement of the investigator would compromise the patients safety or successful participation in the clinical study. Additional exclusion criteria at Visit 3: 24. Any clinically significant abnormality identified on brief physical examination, which in the judgement of the investigator would compromise the patient safety or successful participation in the clinical study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of patients reaching HbA1c target <7% without hypoglycaemia (confirmed or severe) over a 52-week treatment period. |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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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Last visit of the last subject |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |