Clinical Trials Register

Summary
EudraCT Number:	2009-016178-33
Sponsor's Protocol Code Number:	1245.25
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-04-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2009-016178-33

A.3

Full title of the trial

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.

Multicentrické, mezinárodní, randomizované, dvojitě zaslepené klinické hodnocení fáze III s paralelními skupinami hodnotící kardiovaskulární bezpečnost přípravku BI 10773 (10 mg a 25 mg podávaný ústně jednou denně) ve srovnání s obvyklou léčbou pacientů s diabetem mellitus 2. typu se zvýšeným kardiovaskulárním rizikem

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

1245.25

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Boehringer Ingelheim RCV GmbH & Co. KG
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Boehringer Ingelheim Pharma GmbH & Co. KG
B.5.2	Functional name of contact point	QRPE PSC CT Information Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Binger Strasse 173
B.5.3.2	Town/ city	Ingelheim am Rhein
B.5.3.3	Post code	55216
B.5.3.4	Country	Germany
B.5.4	Telephone number	0018002430127
B.5.5	Fax number	0018008217119
B.5.6	E-mail	clintriage.rdg@boehringer-ingelheim.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Empagliflozin
D.3.2	Product code	BI 10773
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Empagliflozin
D.3.9.2	Current sponsor code	BI 10773
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Empagliflozin
D.3.2	Product code	BI 10773
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Empagliflozin
D.3.9.2	Current sponsor code	BI 10773
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

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 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.

E.1.1.1

Medical condition in easily understood language

Type 2 Diabetes mellitus

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

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-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.

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.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.

E.5 End points

E.5.1

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.

E.5.1.1

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

E.5.2

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.

E.5.2.1

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.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

200

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

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

Argentina

Australia

Austria

Belgium

Brazil

Canada

Colombia

Croatia

Czech Republic

Denmark

Egypt

Estonia

France

Georgia

Greece

Hong Kong

Hungary

India

Indonesia

Israel

Italy

Japan

Korea, Republic of

Lebanon

Malaysia

Mexico

Netherlands

Norway

Peru

Philippines

Poland

Portugal

Romania

Russian Federation

Saudi Arabia

Singapore

South Africa

Spain

Sri Lanka

Taiwan

Thailand

Ukraine

United Arab Emirates

United Kingdom

United States

Jordan

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

Provided in the Protocol.

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

2300

F.4.2.2

In the whole clinical trial

7000

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The treatment of subjects after the trial would be the expected normal treatment of their condition.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-07-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-04-13

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials