E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment in type 2 diabetes |
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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 | SOC |
E.1.2 | Classification code | 10027433 |
E.1.2 | Term | Metabolism and nutrition disorders |
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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 efficacy objective of this study is to compare that, after 18 weeks of oral administration of double-blind treatment, the change from baseline in glycosylated haemoglobin A1c (HbA1c) achieved with saxagliptin 5 mg per day added onto metformin is non-inferior to sitagliptin 100 mg per day added onto metformin in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg or higher doses of metformin therapy alone. |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of saxagliptin 5 mg per day versus sitagliptin 100 mg per day given as add on therapy to metformin after 18 weeks of double-blind treatment period by evaluation of: - Change from baseline in FPG, insulin, C-peptide, glucagon and proinsulin - Proportion of patients achieving a therapeutic glycaemic response defined as HbA1c ≤6.5%. - Change from baseline in HbA1c in patients with baseline HbA1c ≥7.0%. - Proportion of patients achieving a therapeutic glycaemic response defined as HbA1c <7.0% in patients whose baseline HbA1c ≥7.0%. - Change from baseline in β-cell function (as measured by HOMA-2 ). - Change from baseline in the AUC from 0 to 180 minutes for postprandial glucose, insulin, C-peptide and glucagon response to an OGTT in a subset of patients. - Change from baseline in postprandial glucose at 120 minutes during OGTT in a subset of patients. - Change from baseline in insulinogenic index in a subset of patients. |
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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 who are ≥ 18 years of age at time of consenting upon Visit 1. 4. Treatment with metformin alone on stable doses of 1500 mg or higher per day for at least 8 weeks prior to Visit 1. 5. 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. 6. HbA1c >6.5% and ≤10.0%. |
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E.4 | Principal exclusion criteria |
Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma. 2. Pregnant or breastfeeding patients. 3. Insulin therapy within one year of enrolment (with the exception of insulin therapy during a hospitalization or use in gestational diabetes). 4. Previous treatment with any DPP-4 inhibitor. 5. Treatment with thiazolidinedione within 12 weeks prior to Visit 1. 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 (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin). 8. Treatment with Human immunodeficiency virus (HIV) treatment/antiviral drugs (delavirdine, indinavir, nelfinavir, ritonavir, saquinavir). 9. Potential allergy to metformin, saxagliptin, sitagliptin, or placebo. 10. Contraindications to therapy as outlined in the saxagliptin IB, metformin package insert, or sitagliptin package insert. 11. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV (see Appendix C) and/or left ventricular ejection fraction of ≤40%. 12. Significant cardiovascular history within the past 6 months upon Visit 1 defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident. 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 both AstraZeneca and Bristol-Myers Squibb staff or staff at the study centre). 16. Previous enrolment or randomization of treatment in the present study. 17. Participation in a clinical study during the last 90 days prior to Visit 1. 18. Donation of blood, plasma or platelets within the past 3 months prior to Visit 1. 19. Any condition where, in the opinion of the investigator, participation in this study may pose a significant risk to the patient or could render the patient unable to successfully complete the study. 20. Suspected or confirmed poor protocol or medication compliance as judged by the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c at week 18. |
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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 | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |