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 |
Short-term: To evaluate the efficacy of saxagliptin 2.5 mg in adult patients with type 2 diabetes and renal impairment (moderate, severe and end-stage) compared with placebo by assessment of the absolute change from baseline in HbA1c and fasting plasma glucose To evaluate the safety and tolerability of saxagliptin 2.5 mg compared with placebo by assessment of AEs, laboratory values, ECG, vital signs, body weight and physical examination To characterize the PK properties of saxagliptin
Long-term: To evaluate the safety and tolerability of sagliptin 2.5 mg compared with placebo by assessment of AEs, laboratory values, ECG, vital signs, body weight and physical examiniation To evaluate the efficacy of oral treatment with saxagliptin 2.5 mg compared with placebo by assessment of the absolute change from baseline in HbA1c and fasting plasma glucose To assess the change from baseline in background anti-diabetic therapy
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At visit 1: Provision of informed consent Diagnosed with type 2 diabetes Men or women who are equal to or above 18 years of age Documented history of CrCl less than 50 ml/min within 3 last months WOCBP using an adequate method of contraception At visit 2: HbA1c above or equal to 7.0% and less than or equal to 11.0% C-peptide level above or equal to 0.375nmol/L, 1.0ng/mL Estimated CrCl less than 50 ml/min contraception for men |
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E.4 | Principal exclusion criteria |
At visit 1: Pregnancy or breastfeeding Initiation of insulin therapy within 4 weeks of study entry or unstable insulin therapy within 4 weeks of study entry Allowed oral antidiabetic therapy that has not been stable within the last 4 weeks Previous or current treatment with any DPP-IV inhibitor and/or GLP-1 mimetic Treatment with metformin within 4 weeks prior to visit 1 Thiazolidinedione treatment that has not been stable within 12 weeks of study entry Systemic treatment with oral prednisolone above 10 mg per day , or comparable dose of systemic glucocorticoid Treatment with CYP450 3A4 inducers, HIV or antiviral drugs Contraindications to therapy as outlined in the saxagliptin IB Congestive heart failure (NYHA) class III or IV and/or left ventricular ejection fraction equal to or less than 40% Significant cardiovascular history within the past 6 months Type I diabetes, history of diabetic ketoacidosis or hypomolar non-ketonic coma History of 2 or more major hypoglycemic events the last 3 months, haemoglobinopathies, alcohol or illegal drug abuse Donation of blood, plasma or platelets within the last 3 months Involvement in planning or conduct of the study Participating in a clinical study within 90 days Unable to complete the study, protocol or medication non-compliant At visit 2: Active liver disease and/or significant abnormal liver function Creatinine kinase above or equal to 3xULN Anemia Clinically significant abnormality Patients receiving peritoneal dialysis, and patients who are expected to initiate peritoneal dialysis within 3 months after enrolment Patients expected to have a kidney transplant within 3 months after enrolment
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E.5 End points |
E.5.1 | Primary end point(s) |
The first 12 weeks of treatment will be used for the primary assessment of treatment effect and tolerability, after which the following 40 weeks will be used to assess the long-term efficacy, safety and tolerability.
The primary variable is absolute change from baseline in HbA1c level at week 12. |
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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 | Yes |
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) | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 | |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |