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: 14 March 2016
• Main ID: EUCTR2009-016178-33-PT
• Date of registration: 20/07/2010
• Prospective Registration: Yes
• Primary sponsor: Unilfarma, Lda.
• 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: 05/11/2010
• Target sample size: 7000
• 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 Number of treatment arms in the trial: 3

Countries of recruitment

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

Contacts

• Name: QRPE pSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim International GmbH

• Name: QRPE pSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim International GmbH

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:
• Confirmed history of myocardial infarction (>2 months prior to informed
consent)
• Evidence of multivessel coronary artery disease, in 2 or more major coronary
arteries, irrespective of the revascularization, ie:
a) Either the presence of a significant stenosis (imaging evidence of at least 50% narrowing of the luminal diameter measured during a coronary angiography or a multi-sliced computed tomography angiography), in 2 or more major coronary arteries,
b) Or a previous revascularisation (percutaneous transluminal coronary angioplasty with or without stent, or coronary artery bypass grafting) at least 2 months ago, in 2 or more major coronary arteries,
c) Or the combination of previous revascularisation in one major
coronary artery at least 2 months ago (percutaneous transluminal
coronary angioplasty with or without stent, or coronary artery bypass
grafting), and the presence of a significant stenosis in another major
coronary artery (imaging evidence of at least 50% narrowing of the
luminal diameter measured during a coronary angiography or a multisliced
computed tomography angiography),
Note: A disease affecting the left main coronary artery is considered as a
2-vessel disease.
• Evidence of a single vessel coronary artery disease with: a) The presence of a significant stenosis i.e. the imaging evidence of at least 50% narrowing of the luminal diameter of one major coronary artery in
patients not subsequently successfully revascularised (measured during a
coronary angiography or a multi-sliced computed tomography angiography)
b) And at least one of the following (either (i) or (ii)):
i. A positive non invasive stress test, confirmed by either:
1. A positive exercise tolerance test in patients without a complete
left bundle branch block, Wolff-Parkinson-White syndrome, or
paced ventricular rhythm, or
2. A positive stress echocardiography showing regional systolic
wall motion abnormalities, or
3. A positive scintigraphic test showing stress-induced ischemia, i.e.
the development of transient perfusion defects during myocardial
perfusion imaging;
ii. Or patient discharged from hospital with a documented diagnosis of
unstable angina within 12 months prior to selection
• Last episode of unstable angina >2 months prior informed consent with
confirmed evidence of coronary multivessel or single vessel disease as
defined above.
• History of ischemic or haemorrhagic stroke (>2 months prior to informed
consent)
• Presence of peripheral artery disease (symptomatic or not) documented by either: previous limb angioplasty, stenting or bypass surgery; or previouslimb or foot amputation due to circulatory insufficiency; or angiographic evidence of significant (> 50%) peripheral artery stenosis in at least one limb; or evidence from a non-invasive measurement of significant (>50% or as reported as hemodynamically significant) peripheral artery stenosis in at least one limb; or ankle brachial index of < 0.9 in at least one limb.
Are
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) 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 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. Intake of an investigational drug in another trial within 30 days prior to intake of study
medication in this trial or participating in another trial (involving an investigational drug
and/or follow-up)
14. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
15. Acute coronary syndrome, stroke or TIA within 2 months prior to informed consent


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: 18.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

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 used is time to the first occurrence of any of
the following adjudicated components of the composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI) and nonfatal stroke.

Secondary Objective: • The time to the first occurrence of the following adjudicated events (treated as a
composite): CV death (including fatal stroke and fatal MI), non-fatal MI
(excluding silent MI), non-fatal stroke and hospitalization for unstable angina
pectoris.
Further secondary endpoints are the occurrence of and time to each of the
following events:
• Silent MI.
• Heart failure requiring hospitalization
• New onset albuminuria defined as ACR = 30 mg/g
• New onset macroalbuminuria =300 mg/g
• Composite microvascular outcome defined as:
1) Need for retinal photocoagulation
2) Vitreous haemorrhage
3) Diabetes-related blindness
4) New or worsening nephropathy defined as:
4a) New onset of macroalbuminuria; or 4b) Doubling of serum creatinine
level accompanied by an eGFR (based on modification of diet in renal
disease (MDRD) formula) = 45 mL/min/1.73m2; or 4c) Need for continuous
renal replacement therapy; or d) death due to renal disease.

Timepoint(s) of evaluation of this end point: Change from baseline in: HbA1c, Fasting Plasma Glucose (FPG), weight, waist
circumference and blood pressure at weeks 12, 52, once a year and end of study.

Primary end point(s): The primary endpoint used is time to the first occurrence of any of
the following adjudicated components of the composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI) and nonfatal
stroke.

Secondary Outcome(s)

Secondary end point(s): The time to the first occurrence of the following adjudicated events (treated as a
composite): CV death (including fatal stroke and fatal MI), non-fatal MI (excluding
silent MI), non-fatal stroke and hospitalization for unstable angina pectoris.

Timepoint(s) of evaluation of this end point: Change from baseline in: HbA1c, Fasting Plasma Glucose (FPG), weight, waist
circumference and blood pressure at weeks 12, 52, once a year and end of study.

Secondary ID(s)

2009-016178-33-NL

1245.25

Source(s) of Monetary Support

Unilfarma, Lda.

Boehringer Ingelheim International GmbH