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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 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 |
The study will be declared positive if at least one of the two hypotheses is significant: 1. to evaluate the efficacy of vildagliptin as initial or add-on therapy in elderly patients with T2DM who are drug-naive or inadequately controlled with oral anti-diabetic agents (OADs) by testing the hypothesis that the HbA1c reduction with vildagliptin is superior to that of placebo after 24 weeks of treatment. 2. to evaluate the proportion of elderly patients with T2DM who are drug-naive or inadequately controlled with OADs by testing the hypothesis that the proportion of patients reaching their investigator-defined individual target HbA1c while being treated with vildagliptin is superior to that of placebo after 24 weeks of treatment
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E.2.2 | Secondary objectives of the trial |
•to evaluate the safety and tolerability of vildagliptin as initial or add-on therapy in elderly patients with T2DM who are drug-naive or inadequately controlled with OADs during 24 weeks. •to evaluate the efficacy of vildagliptin as initial or add-on therapy in elderly patients with T2DM who are drug-naive or inadequately controlled with OAD by testing the hypothesis that the FPG reduction with vildagliptin is superior to that of placebo after 24 weeks of treatment. •to assess the responder rates of vildagliptin, as compared to placebo, in elderly patients with T2DM who are drug-naive or inadequately controlled with OADs.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•age: ≥ 70 years inclusive at Visit 1. •female or male. •patients with a confirmed diagnosis of T2DM: i/treated with a stable dose of OADs for at least 12 weeks prior to Visit 1. OADs that are allowed in this study are metformin, sulfonylurea (SU), thiazolidinediones (TZDs), α-glucosidase inhibitors or meglitinides, used either as monotherapy or in combination. ii/drug-naive patients diagnosed at least 12 weeks prior to Visit 1 (drug-naive is defined as no treatment with OADs for at least 12 weeks prior to Visit 1 and no treatment with OADs for > 3 consecutive months at any time in the past). • HbA1c of ≥ 7% and ≤10.0% by central laboratory at Visit 1 and assessed by the investigator to be inadequately controlled. • body mass index (BMI) in the range of 19-45 kg/m2 inclusive at Visit 1. • agreement to maintain a stable background medication dose throughout the study, if currently receiving OADs.
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E.4 | Principal exclusion criteria |
• FPG ≥270mg/dL (15mmol/L) at Visit 1. • use of any of the following medications as assessed at Visit 1: - prior use of insulin treatment (for ≥ 7 consecutive days) in the preceding 12 weeks. - use of DPP-4 inhibitors or GLP-1 analogues in the preceding 12 weeks. - use of weight control products including weight-loss medications in the last 12 weeks. - use of oral (≥7 consecutive days) or chronic parenteral or intra-articular corticosteroid treatment within the last 8 weeks. - treatment with growth hormone within the previous 6 months. - treatment with any drug of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study. • a history or evidence of any of the following: - acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including coma) within the past 6 months. - current diagnosis of congestive heart failure (NYHA III or IV). - myocardial infarction within the past 6 months. - coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months. - Stroke, transient ischemic attack, or reversible ischemic neurologic deficit within the past 6 months. - unstable angina within the past 3 months. - sustained and clinically relevant ventricular arrhythmia (patients with premature ventricular contractions if deemed not clinically significant may be enrolled). - type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing’s syndrome or acromegaly-associated diabetes). - malignancy of an 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 local recurrence or metastases. - hepatic disorder defined as: - acute or chronic liver disease, evidence of hepatitis, cirrhosis or portal hypertension. - history of imaging abnormalities that suggest liver disease (except hepatic steatosis), such as portal hypertension, capsule scalloping, cirrhosis. - acute infections which may affect blood glucose control within the past 4 weeks. •any of the following significant laboratory abnormalities as assessed at Visit 1 - clinically significant elevation or reduction of thyroid stimulating hormone (TSH) outside of the normal range. - clinically significant renal dysfunction: glomerular filtration rate (GFR) <30mL/min/1.73m2 (via modification of diet in renal disease (MDRD) formula). - alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Visit 1, confirmed by repeat measure within 3 working days. - total bilirubin > 2 x ULN and/or direct bilirubin > 1 x ULN confirmed by repeat measure within 3 working days. - positive Hepatitis B surface antigen (HBsAg). - positive Hepatitis C virus (HCV) antibody test (anti-HCV). - elevated fasting triglycerides (TGs) > 500mg/dL (5.65mmol/L). • any of the following electrocardiographic abnormalities at Visit 1 - second or third degree atrio-ventricular block without a pacemaker. - long QT syndrome or QTc > 500ms. •history of hypersensitivity to DPP-4 inhibitors.
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E.5 End points |
E.5.1 | Primary end point(s) |
• HbA1c reduction. • percentage of patients reaching individual HbA1c target at week 24 or end of study.
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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 | 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) | 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 | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |