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 | 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 |
To compare that after 52-week oral administration of double-blind treatment, the absolute change from baseline in glycosylated haemoglobin A1c (HBA1c) level with saxagliptin plus metformin is non-inferior to glipizide (sulphonylurea) plus metformin in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg or higher doses of metformin alone. |
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E.2.2 | Secondary objectives of the trial |
Three secondary objectives among all secondary objectives, are identified a priori for special attention to compare the effects of saxagliptin versus glipizide given as add-on therapy to metformin after a 52-week double-blind treatment period by evaluation of: - Proportion of patients reporting at least one episode of hypoglycaemic event at week 52. - Change from baseline in body weight at week 52. - Durability of HbA1c effect based on week 24 over the 52 weeks as an efficacy objective |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent 2. Diagnosed with type 2 diabetes 3. Men or women above or equal to 18 years 4. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such manner that the risk of pregnancy is minimized. Adequate method of contraception is defined as a method of contraception with a failure rate (Pearl Index) of < 1% (combined pills, tubal sterilization, IUD, 1 and 3 month injectable, subdermal implant, transdermal patch). 5. Treatment with metformin alone on a stable dose of 1500 mg or higher per day for at least 8 weeks prior to visit 1 6. HbA1c higher than 6.5% and less than or equal to 10.0% at lead in visit |
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E.4 | Principal exclusion criteria |
1. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma 2. Pregnant or breastfeeding patients 3. Insulin therapy within 1 year of enrolment 4. Previous treatment with any DPP-4 inhibitor 5. Treatment with thiazolidindione within 12 weeks prior to visit 1 6. Treatment with systemic glucocorticoids other than replacement therapy 7. Treatment with Cytochrome P450 3A4 inducers 8. Treatment with human immunodeficiency virus (HIV) treatment 9. Potential allergy to metformin, saxagliptin, glipizide, or placebo or excipients 10. Congestive heart failure 11. Significant cardiovascular history 12. History of haemoglobinopathies 13. History of alcohol abuse or illegal drug abuse within the past 12 months 14. Involvement in the planning and conduct of the study 15. Previous enrolment or randomization of treatment in the present study 16. Participation in a clinical study during the last 90 days prior to visit 1 17. Donation of blood, plasma or platelets within the past 3 months prior to visit 1 18. Any condition where, in the opinion of the investigator, participation in this study may pose a significant risk to the patient (such as severe macro- or microvascular complications), or could render the patient unable to successfully complete the study. 19. Suspected or confimed poor protocol or medication compliance
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome variable is the change from baseline in HbA1c at 52 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 | Yes |
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 | 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 | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 125 |
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 | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |