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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - 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 |
• To evaluate the effect of vildagliptin on left ventricular function in patients with T2DM and CHF (NYHA class I-III) by showing that vildagliptin is at least not inferior to placebo with respect to change in left ventricular ejection fraction (LVEF) after 52 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the overall safety and tolerability of vildagliptin versus placebo in patients with T2DM and CHF (NYHA class I – III) over 52 weeks of treatment with special regards to signs and symptoms of heart failure. • To evaluate the efficacy of vildagliptin in patients with T2DM and CHF (NYHA class I-III) by assessing the HbA1c reduction with vildagliptin compared to placebo after 16 weeks of treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must give written informed consent before any assessment is performed. 2. Patients 18-85 years old (inclusive) at Visit 1. 3. Patients with T2DM, diagnosed at least 3 months prior to Visit 1, either untreated (defined as not taking anti-diabetic therapy for at least 8 weeks prior to Visit 1) or treated with anti-diabetic therapy (defined as metformin, sulfonylurea, insulin, alpha-glucosidase inhibitors, or glinides as monotherapy or combination therapy for at least 8 weeks prior to Visit 1) and maintaining dietary advice and exercise habits during the full course of the study. 4. Stable dose of anti-diabetic therapy over the past 4 weeks prior to Visit 1 (stable insulin therapy is defined as ± 20% of total daily units) for patients on anti-diabetic treatment. 5. CHF (NYHA Class I, Class II, or Class III) at Visit 1. • Treatment of heart failure should be according to guidelines (SCC/SHS 2005) (ESC/EASD 2007) and dosage of beta-blockers, angiotensin converting enzyme-inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) should have been stable for one month prior to visit 1. 6. LVEF < 40% (results must be available at Visit 2, prior to randomization) 7. HbA1c in the range of ≥ 6.5% to 10% at Visit 1. 8. Body Mass Index (BMI) in the range of 22-42 kg/m2, inclusive, at Visit 1.
For detailed inclusion criteria, please refer to the full protocol. |
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E.4 | Principal exclusion criteria |
1. Fasting Plasma Glucose (FPG) ≥ 270 mg/dL (15 mmol/L) at Visit 1. 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). 3. A history of: • type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly. • acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months. 4. Patients that have been enrolled in a vildagliptin clinical trial or taken other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within 6 months prior to visit 1. 5. Patients taking vildagliptin at any time. 6. Patients taking thiazolidinediones (TZDs). TZDs given up to 6 months prior to Visit 1 are allowed. 7. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study 8. Any of the following within the past 6 months: • myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor); • coronary artery bypass surgery or percutaneous coronary intervention • unstable angina • stroke 9. Any of the following ECG abnormalities: • Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation • second degree AV block (Mobitz 1 and 2); patients with pacemakers are not excluded. • third degree AV block; patients with pacemakers are not excluded. • prolonged QTc (> 500 ms) per Bazetts method 10. GFR (estimated by Cockcroft-Gault formula) < 30 mL/min at Visit 1. 11. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin),treated or untreated, within the past 5 years, regardless of whether there is evidence of localrecurrence or metastases. 12. Liver disease, such as cirrhosis, or chronic active hepatitis B or C (as defined in exclusion criteria no. 15). 13. Concurrent medical condition that may interfere with the interpretation of safety and efficacy data during the study. 14. Any of the following concomitant medications: • any anti-diabetic drug therapy other than metformin, sulfonylurea, insulin, alpha-glucosidase inhibitors, or glinides therapy (as monotherapy or combination) within 8 weeks or TZDs within 6 months prior to visit 1 • chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1 • treatment with growth hormones or similar drugs • treatment with any medication (other than metformin) that is contraindicated in the CHF (NYHA class I-III) population • use of other investigational drugs within 30 days or 5 half-lives of the drug at visit 1, which ever is longer, unless local health authority guidelines mandate a longer period • treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e. cytostatic drugs) 15. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 16. Any of the following significant laboratory abnormalities: • Evidence of active hyper or hypothyroidism interpreted as serum free T4 (thyroid hormone) level outside the normal range in patient who have abnormal serum thyroid stimulating hormone (TSH) outside of normal range at visit 1 • Clinical significant laboratory abnormalities in the opinion of the investigator • Elevated fasting triglycerides > 500 mg/dl at Visit 1 • ALT and/or AST > 2 x ULN at Visit 1, confirmed by repeat measure within 3 working days • Total bilirubin > 2 x ULN and/or direct bilirubin > 1 x ULN at Visit 1, confirmed by repeat measure within 3 working days • Positive Hepatitis B surface test (antigen - HbsAg) at Visit 1 • Positive Hepatitis C antibody test (HCV antibodies) at Visit 1 17. Any medical condition that causes heart failure in which there is an indication for either a surgical intervention or a medical intervention that would result in the resolution of the heart failure. 18. Donation of one unit (500 mL) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks, or a blood transfusion within the past 8 weeks. 19. History of active substance abuse (including alcohol and alcohol related hepatic disease) within the past 2 years. 20. Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome variable is change from baseline in LVEF (%) at Week 52, regardless of rescue medication use. Baseline is the measurement obtained on the day of Screening (Week -2, Visit 1). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 26 |
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 | 24 |
E.8.9.2 | In all countries concerned by the trial days | 26 |