E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes mellitus tipo 2 no insulino dependiente
Non-insulin dependent type 2 diabetes mellitus |
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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 show the superiority of saxagliptin 5 mg once daily added on to metformin 1500 mg daily, compared to metformin uptitrated to a maximum of 2500 mg daily in improving glycaemic control, as determined by the absolute change in HbA1c levels from baseline to Week 24, in patients with type 2 diabetes who have inadequate glycaemic control on a submaximal total daily dose of 1500 mg of metformin |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to compare the effects of saxagliptin 5 mg once daily added on to metformin 1500 mg daily, compared to metformin uptitrated to a maximum dose of 2500 mg daily after 24-weeks of treatment by evaluation of the secondary efficacy and safety endpoints described below:
Efficacy - Change from baseline to Week 24 in FPG and fasting-insulin - Proportion of patients achieving a therapeutic glycaemic response at Week 24 defined as HbA1c <7.0% or <6.5% - Change from baseline to Week 24 in beta-cell function as measured by Homeostasis Model Assessment-beta (HOMA-beta)
Safety - Safety and tolerability will be evaluated by assessment of adverse events (AEs), laboratory values, electrocardiogram (ECG), vital signs (pulse, blood pressure), body weight, height and physical examination - Rates of hypoglycaemic events (number of confirmed hypoglycaemic events per unit of time, eg, week or month) |
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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 see if a new investigational drug in addition to background metformin is effective and safe in treating type 2 diabetes and if so, how it compares to a higher (uptitrated) dose of metformin |
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E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures. 2. Men or women who are >/=18 years of age at time of consenting upon Visit 1. 3. Clinical diagnosis of type 2 diabetes. 4. Treatment with metformin alone (any formulation) on stable doses of 1500 to 1700 mg 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 a manner that the risk of pregnancy is minimized. - WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >/=12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35 mIU/mL). - Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (eg, vasectomy), should be considered to be of childbearing potential. 6. HbA1c >/=7.0% and </=10.0%. |
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E.4 | Principal exclusion criteria |
1. Any clinically significant abnormality identified on physical examination or laboratory tests that would compromise patients safety or successful participation in the study as judged by the investigator. 2. Patients who have previously been intolerant to or non-compliant with a total daily dose of metformin higher than 1500 to 1700 mg. 3. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma. 4. Pregnant or breastfeeding patients. 5. Prior use of insulin or injectable GLP-1 analogue (exenatide or liraglutide) within 3 months of the study start. 6. Treatment with systemic glucocorticoids other than replacement therapy. Inhaled, local injected and topical use of glucocorticoids are allowed. 7. Treatment with cytochrome P450 3A4 (CYP450 3A4) inducers, eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin and St. Johns Worth, and cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitors, eg, delavirdine, indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole (topical use is allowed), nefazodone, saquinavir and telithromycin. 8. Potential allergy to saxagliptin, placebo or formulation excipients. 9. Past hypersensitivity reaction to a DPP-4 inhibitor. 10. Contraindications to therapy as outlined in the saxagliptin Investigators Brochure. 11. Contraindications to therapy as outlined in the metformin package insert including conditions leading to an increased risk of hypoxemia and lactic acidosis. 12. History of haemoglobinopathies (sickle cell anaemia or thalassemias, sideroblastic anaemia). 13. History of alcohol abuse or illegal drug abuse within the past 12 months. 14. Involvement in the planning and conduct of the study (applies to both AstraZeneca and Bristol-Myers Squibb personnel or personnel at the study centre). 15. Participation in a clinical study during the past 3 months prior to Visit 1. 16. Donation of blood, plasma or platelets within the past 3 months prior to Visit 1. 17. 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. 18. Suspected or confirmed poor protocol or medication compliance as judged by the investigator. Additional Exclusion criteria at Visit 2: 19. Serum creatinine >/=133 μmol/L (>/=1.5 mg/dL) for men or >/=124 μmol/L (>/=1.4 mg/dL) for women. 20. Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3xULN and/or total bilirubin >34 μmol/L (>2.0 mg/dL). 21. Creatine kinase (CK) >/=10xULN. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change from baseline in HbA1c at Week 24. |
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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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | 1 |
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 | 1 |
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 |