E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus, inadequate glycaemic control |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
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 aim of this study is to evaluate the safety and efficacy of therapy with saxagliptin 5mg co-administered with dapagliflozin 5mg, compared to therapy with saxaglipgtin 5mg or dapagliflozin 5mg in adult patients with type 2 diabetes who are inadequately controlled on ≥1500mg/day of metformin monotherapy.
The primary objective is to demonstrate the superiority of the change from baseline HbA1c achieved with the co-administered saxagliptin 5mg and dapagliflozin 5mg to either agent individually after 24 weeks.
The primary safety objective is to evaluate the safety and tolerability of the co-administered saxagliptin 5mg and dapagliflozin 5mg to either agent individually after 24 weeks. |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate the effect of co-administered saxagliptin 5mg and dapagliflozin 5mg to either agent individually on proportion of patients achieving therapeutic glycaemic response after 24 weeks.
2. To demonstrate the effect of co-administered saxagliptin 5mg and dapagliflozin 5mg to either agent individually on fasting plasma glucose after 24 weeks.
3. To demonstrate the effect of co-administered saxagliptin 5mg and dapagliflozin 5mg to saxagliptin 5mg on total body weight after 24 weeks |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients aged ≥18 years old at time of informed consent;
2. Patients with T2DM defined as HbA1C≥7.5% to ≤10.0% at screening visit;
3. Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg per day;
4. BMI ≤45.0kg/m2 at Enrolment visit. |
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E.4 | Principal exclusion criteria |
1. History of diabetes insipidus, Type 1 diabetes or Latent Autoimmune Diabetes of Adults, diabetic ketoacidosis or hyperosmolar nonketotic coma and Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to Enrolment (Visit 1), or other signs and symptoms.
2. History of pancreatitis.
3. Administration of any antihyperglycaemic therapy, other than metformin, for more than 14 days (consecutive or not) during the 8 weeks prior to enrolment
4. Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment
5. Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency and/or significant abnormal liver function, including patients with ALT and/or AST ≥3x ULN and/or Total Bilirubin ≥2.0x ULN. History of severe hepatobiliary disease or hepatotoxicity with any medication. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for Hepatitis viral antibody IgM, Hepatitis B surface antigen, and Hepatitis C virus antibody.
6. Moderate or severe impairment of renal function [defined as eGFR <60mL/min/1.73 m2 (estimated by MDRD) or serum creatinine ≥1.5mg/dL in males or ≥1.4mg/dL in females]. Conditions of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.
7. History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline HbA1c to week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Proportion of patients achieving HbA1c < 7.0%, after 24 weeks;
2. Change in fasting plasma glucose from baseline to 24 weeks;
3. Change in total body weight from baseline to 24 weeks. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 26 |
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 | No |
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 |
Canada |
Czech Republic |
Germany |
Mexico |
Russian Federation |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |