E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study will be performed in patients with type 2 diabetes mellitus and high cardiovascular risk who have insufficient glycaemic control |
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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 | 10045242 |
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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 objective of the current study is to demonstrate non inferiority of two doses of BI 10773 (10 mg/daily and 25 mg/daily) compared to placebo with respect to first occurrence of any of the adjudicated components of the primary composite Major Adverse Cardiovascular Event endpoint (cardiovascular death, non fatal stroke, nonfatal myocardial infarction) in patients with type 2 diabetes mellitus and increased cardiovascular risk. |
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E.2.2 | Secondary objectives of the trial |
Key secondary cardiovascular-endpoint: 1)The composite of all events adjudicated: CV death (including fatal stroke and fatal MI), non-fatal MI, non-fatal stroke and hospitalization for unstable anginapectoris 2)the occurrence of and time to each of the following events: -To determine the incidence of silent MI. -To determine the incidence of microalbuminuria and the progression of microalbuminuria to macroalbuminuria from baseline to end of trial. 3)The occurrence of and time to each of the following adjudicated events: -CV death (including fatal stroke and fatal MI) -non-fatal MI -non-fatal stroke -Hospitalization due to cardiac heart failure -All cause mortality -TIA -coronary revascularization procedures -changes from baseline in ECG, physical examination, vital signs and laboratory parameters -Adverse events -Hypoglycaemic events -Protocol-specified significant adverse events -Use of rescue medication |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Diagnosis of type 2 diabetes mellitus prior to informed consent 2.Male and female patients on diet and exercise regimen who are drug-naive or pre-treated with any background therapy. Antidiabetic therapy has to be unchanged for 12 weeks prior to randomization. If insulin is part of the background therapy, the insulin dose should not be changed within the 12 weeks prior to randomisation by more than 5% daily from the baseline value at randomisation 3. HbA1c of >=7.0% and <=10% at Visit 1 (screening) for patients on background therapy or HbA1c of >=7.0% and <=8.0% At Visit 1 (screening) for drug-na�ve patients. 4.Age >=18 years 5.BMI <=45 kg/m**2 (Body Mass Index) at Visit 1 (Screening) 6.Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation 7.In addition to the above described criteria, patients must have high cardiovascular risk, defined as at least one of the following: -History of myocardial infarction (>2 months prior to informed consent) -Unstable angina (>2 months prior informed consent) with documented multivessel coronary disease (of at least two major coronary arteries in angiogram) or positive stress test (ST segment depression >= 2 mm or a positive nuclear perfusion scintigram) -Multivessel Percutaneous Coronary Intervention (PCI) >2 months prior informed consent -Multivessel Coronary Artery By-pass Grafting (CABG) >4 years prior to informed consent or with recurrent angina following surgery • History of ischemic or hemorrhagic stroke (>2 months prior to informed consent) • Peripheral occlusive arterial disease (previous limb bypass surgery or percutaneous transluminal angioplasty; previous limb or foot amputation due to circulatory insufficiency, angiographic or imaging detected (for example: ultrasound, MRI) significant vessel stenosis (>50% stenosis) of major limb arteries) |
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E.4 | Principal exclusion criteria |
1.Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day) 2.Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run in phase. 3.Planned cardiac surgery or angioplasty within 3 months 4.Impaired renal function, defined as GFR<30 ml/min (severe renal impairment, MDRD formula) as determined during screening and/or run in phase. 5.Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption 6.Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia) 7.Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years 8.Contraindications to background therapy according to the local label 9.Treatment with anti-obesity drugs (e.g., sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight 10.Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM 11.Pre-menopausal women (last menstruation <= 1 year prior to informed consent) who: - are nursing or pregnant or - are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local Authorities), double barrier method and vasectomised partner 12.Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake 13.Participation in another trial with an investigational drug within 30 days prior to informed consent 14.Any other clinical condition that would jeopardize patients safety while participating in this clinical trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
The time to the first occurrence of any of the following adjudicated components of the primary composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal MI and non-fatal stroke. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |