E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 up-titrated 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 |
To compare the effects of saxagliptin 5 mg once daily added on to metformin 1500 mg daily, compared to metformin up-titrated to a maximum 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 fasting plasma glucose (FPG) and fasting insulin and β-cell function as measured by Homeostasis Model Assessment-β (HOMA-β) − Proportion of patients achieving a therapeutic glycaemic response at Week 24 defined as HbA1c <7.0% or <6.5%
Safety: − Safety and tolerability will be evaluated by assessment of adverse events, laboratory values, electrocardiogram (ECG), pulse, blood pressure, body weight, height and physical examination − Rates of hypoglycaemic events (number of confirmed hypoglycemic episodes per unit of time, eg, week or month) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent. 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 patient’s 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. John’s Worth. 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 Investigator’s Brochure.
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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 | 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) | Yes |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 13 |
E.8.9.2 | In all countries concerned by the trial days | 0 |