BI 10773 Cardiovascular outcome event trial in Type 2 Diabetes Mellitus patients

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2009-016178-33-DK
• Date of registration: 16/06/2010
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim Pharmaceuticals, Inc.
• Public title: BI 10773 Cardiovascular outcome event trial in Type 2 Diabetes Mellitus patients
• 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: 06/07/2010
• 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

Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Croatia, Czech Republic, Denmark, Estonia, France, Georgia, Greece, Hong Kong, Hungary, India, Indonesia, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sri Lanka, Taiwan, Thailand, Ukraine, United Kingdom, United States

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG

Key inclusion & exclusion criteria

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-naïve 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 total daily prescribed dose should not be changed within the 12 weeks prior to randomisation by more than 10% 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 =9.0% At Visit 1 (screening) for drug-naïve patients; 4.Age =18 years; 5. BMI =45 kg/m2 at Visit 1 (Screening); 6.Signed and dated written informed consent by date of Visit 1; 7. In addition to the above described criteria, patients must have high CV 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 status, i.e.
•Evidence of a single vessel coronary artery disease; •Last episode of unstable angina (>2 months prior informed consent) with confirmed evidence of coronary multivessel or single vessel disease.
•History of ischemic or haemorrhagic stroke (>2 months prior to informed consent)
•Presence of peripheral occlusive arterial artery disease (symptomatic or not ) documented by either : previous limb angioplasty, stenting or bypass surgery; or previous limb 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 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 7000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2100

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.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: Empagliflozin
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
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: Empagliflozin
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
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)

Primary end point(s): The primary endpoint is 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 myocardial infarction (excluding silent MI), and non-fatal stroke.

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 (excluding silent MI) and non-fatal stroke.

Secondary Objective: The key secondary cv-endpoint is the composite of the following adjudicated events: CV death (including fatal stroke and fatal MI), nonfatal MI (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris. Aditional secondary endpoints are the occurrence of and time to each of the following events: • Silent MI; •Hospitalization due to heart failure; • New onset albuminuria defined as ACR > 30 mg/g; • New onset macroalbuminuria >300 mg/g • Composite microvascular outcome defined as: 1-Initiation of retinal photocoagulation, 2-Vitreous haemorrage, 3-Diabetes-related blindness;
or 4-New or worsening nephropathy defined as 4a-New onset of macroalbuminuria;4b-Doubling of serum creatinine level accompanied by
an eGFR<=45ml/min/1.73m2; or 4c-Initiation of continuous renal replacementtherapy; or 4d-Death due to renal disease.

Timepoint(s) of evaluation of this end point: The primary analysis will be based on the treated set after a minimum of 691 3-point Major Adverse Cardiovascular events (MACE) have occurred to be able to comply with the objective of the trial

Secondary Outcome(s)

Secondary end point(s): The key secondary endpoint, which is part of the testing strategy, is the composite of all of the following adjudicated events: 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: After a minimum of 691 3-point Major Adverse Cardiovascular events (MACE) have occurred to be able to comply with the objective of the trial.

Secondary ID(s)

2009-016178-33-NL

1245.25

Source(s) of Monetary Support

Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Danmark A/S