E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
type 2 diabetes and congestive heart failure |
|
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 | 10012647 |
E.1.2 | Term | Diabetic cardiomyopathy |
|
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 |
Primary objective: 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. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives: 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 regard 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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: Patients must give written informed consent before any assessment is performed. Patients 18-85 years old (inclusive) at Visit 1. 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) and maintaining diet and exercise habits during the full course of the study or treated with anti-diabetic therapy (defined as 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. 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. CHF (NYHA Class I, Class II, or Class III) at Visit 1. Treatment of heart failure if required should be according to guidelines [ACC/AHA 2005], [ESC/EASD 2007]. LVEF < 40% (results must be available at Visit 2, prior to randomization) HbA1c in the range of > 6.5% to 10% at Visit 1. Body Mass Index (BMI) in the range of 22-42 kg/m2, inclusive, at Visit 1. Male, non-fertile female or female of childbearing potential using a medically approved birth control method. PLS SEE PROTOCOL |
|
E.4 | Principal exclusion criteria |
Exclusion criteria: Fasting Plasma Glucose (FPG) &#8805; 270 mg/dL (15 mmol/L) at Visit 1. 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). A history of: type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushings syndrome and acromegaly. acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months. Patients that have been enrolled in a vildagliptin clinical trial or taken part in other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within 6 months prior to visit 1. Patients taking vildagliptin at any time.. Patients taking thiazolidinediones (TZDs). TZDs given up to 12 months prior to Visit 1 would be allowed. 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 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 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. PLS SEE PROTOCOL |
|
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). |
|
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) | 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 | No |
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 | 4 |
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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |