A Phase III, multicentre, international, randomised, parallel group, double blind cardiovascular safety study of BI 10773 (10 mg and 25 mg administered orally once daily) compared to usual care in type 2 diabetes mellitus patients with increased cardiovascular risk.

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2009-016178-33-FR
• Date of registration: 09/07/2010
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim France
• Public title: A Phase III, multicentre, international, randomised, parallel group, double blind cardiovascular safety study of BI 10773 (10 mg and 25 mg administered orally once daily) compared to usual care in type 2 diabetes mellitus patients with increased cardiovascular risk.
• Scientific title: A Phase III, multicentre, international, randomised, parallel group, double blind cardiovascular safety study of BI 10773 (10 mg and 25 mg administered orally once daily) compared to usual care in type 2 diabetes mellitus patients with increased cardiovascular risk.
• Date of first enrolment: 17/08/2010
• Target sample size: 4000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016178-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Estonia, France, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of T2DM
2. Male and female patients on diet and exercise regimen who are drug-naïve or pre-treated with any background therapy.
3. HbA1c of = 7.0% and = 10% for patients on background therapy
4. HbA1c of = 7.0% and = 8.0% for drug-naïve patients.
5. Age >18 years
6. BMI = 45 kg/m2 at Visit 1 (Screening)
7. Signed and dated written informed consent (IC) by date of Visit 1
8. Patients must have high cardiovascular risk, defined as at least one of the following:
• History of myocardial infarction (> 2 months prior to IC)
• Unstable angina (> 2 months prior IC)
• Multivessel Percutaneous Coronary Intervention (PCI) > 2 months prior IC
• Multivessel Coronary Artery By-pass Grafting (CABG) > 4 years prior to IC or with recurrent angina following surgery
• History of ischemic or hemorrhagic stroke (> 2 months prior to IC)
• 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 significant vessel stenosis of major limb arteries)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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
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 (MDRD formula)
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 3 months prior to informed consent or any other treatment at the time of screening leading to unstable body weight
10. Current treatment with systemic steroids at time of IC or change in dosage of thyroid hormones within 6 weeks prior to IC or any other uncontrolled endocrine disorder except T2D
11. Pre-menopausal women (last menstruation =1 year prior to IC) who:
- are nursing or pregnant or
- are of child-bearing potential and are not practicing an acceptable method of birth control
12. Alcohol or drug abuse within the 3 months prior to IC
13. Participation in another trial with an investigational drug within 30 days prior to IC
14. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

The study will be performed in patients with type 2 diabetes mellitus and high cardiovascular risk who have insufficient glycaemic control despite diet and exercise and are either treatment naïve or receiving any antidiabetic background therapy. Drug-naïve is defined as absence of any antidiabetic therapy for 12 weeks prior to randomisation.
MedDRA version: 12.1 Level: LLT Classification code 10067585 Term: Type 2 diabetes mellitus

Intervention(s)

Product Name: BI 10773
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
CAS Number: 864070-44-0
Current Sponsor code: BI 10773
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: BI 10773
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
CAS Number: 864070-44-0
Current Sponsor code: BI 10773
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary endpoint is 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.

Primary end point(s): The primary endpoint used in the primary analysis is 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.

Secondary Objective: 1.- Occurrence of and time to the following composite endpoint consisting of following adjudicated events:
• CV death (including fatal stroke and fatal MI), non-fatal MI, non-fatal stroke and hospitalization for unstable angina pectoris.

2.- Occurrence of and time to each of the following events:
• Incidence of microalbuminuria and the progression of microalbuminuria to macroalbuminuria.
• Incidence of silent MI.

3.- 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 therapy

Secondary ID(s)

1245.25

2009-016178-33-NL