Clinical Trials Register

Summary
EudraCT Number:	2010-021375-92
Sponsor's Protocol Code Number:	1276.1
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-06-22
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

Spain - AEMPS

A.2

EudraCT number

2010-021375-92

A.3

Full title of the trial

A 24-week phase III randomized, double-blind, parallel group study to evaluate the efficacy and safety of twice daily oral administration of empagliflozin + metformin compared with the individual components of empagliflozin or metformin in drug naive patients with type 2 diabetes mellitus

Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, de 24 semanas para evaluar la eficacia y seguridad de la administración oral, dos veces al día, de empagliflozina + metformina en comparación con los componentes individuales, empagliflozina o metformina, en pacientes naive con diabetes mellitus de tipo 2.

A.3.1

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

Safety and efficacy study of empagliflozin and metformin for 24 weeks in treatment naive patients with type 2 diabetes

Estudio de 24 semanas para evaluar la eficacia y seguridad de empaglifozina y metformina en pacientes naive con diabetes mellitus de tipo 2.

A.4.1

Sponsor's protocol code number

1276.1

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 España, S.A.
B.1.3.4	Country	Spain
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	Boehringer Ingelheim España, S.A.
B.4.2	Country	Spain
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	+1-800-243-0127
B.5.5	Fax number	+1-800-821-7119
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	2.5
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	5
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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.IMP: 4
D.1.2 and D.1.3	IMP Role	Comparator
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: 5
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	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	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
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	500
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: 6
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	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	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	850
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: 7
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	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	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
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	1000
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: 8
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Santé S.A.S.
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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.3.4	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	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
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	500
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: 9
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Santé S.A.S.
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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.3.4	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	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	850
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: 10
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Santé S.A.S.
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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.3.4	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	METFORMIN HYDROCHLORIDE
D.3.9.1	CAS number	1115-70-4
D.3.9.4	EV Substance Code	SUB03200MIG
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	1000
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
D.8 Placebo: 3
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: 4
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: 5
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: 6
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: 7
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

Type 2 diabetes mellitus

Diabetes mellitus tipo 2

E.1.1.1

Medical condition in easily understood language

non-insulin-dependent increase in blood sugar

Aumento del azúcar en sangre no dependiente de insulina

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II 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 objective of the study is to investigate the efficacy and safety of empagliflozin 5 mg bid + metformin 500 mg bid, empagliflozin 5 mg bid + metformin 1000 mg bid, empagliflozin 12.5 mg bid + metformin 500 mg bid and empagliflozin 12.5 mg bid + metformin 1000 mg bid compared with the individual components of empagliflozin (10 mg or 25 mg qd) or metformin (500 mg or 1000 mg bid) in patients with T2DM treated with diet and exercise with insufficient glycemic control.
The objective of the open-label part is to estimate the efficacy and safety of empagliflozin 12.5 mg bid + metformin 1000 mg bid for 24 weeks in patients with very poor glycemic control.

El objetivo del estudio es investigar la eficacia y seguridad de empaglifozina 5mg bid+metformina 500 mg bid, empaglifozina 5 mg bid+ metformina 1000 mg bid, empaglifozina 12,5 mg bid + metformina 500 mg bid y empagliflozina 12,5 mg bid + metformina 1000 mg bid comparado con los componentes individuales de empagliflozina (10 mg o 25 mg qd) o metformina (500 mg o 1000 mg bid) en pacientes con diabetes mellitus tipo 2 tratados con dieta y ejercicio con insuficiente control glucémico.
El objetivo de la parte abierta es estimar la eficacia y seguridad de empagliflozina 12,5 mg bid + metformina 1000 mg bid durante 24 semanas en pacientes con control glucémico muy pobre.

E.2.2

Secondary objectives of the trial

Not applicable.

No aplica.

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-naive, defined as absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomization
3. HbA1c
a. ? 7.0% and ? 10% (?53.0 mmol/mol and ?85.8 mmol/mol) at Visit 1 (screening) to be eligible for randomized treatment
b.> 10.0% (>85.8 mmol/mol) at Visit 1 (screening) to be eligible for the open-label arm
4. Age ? 18
5. Body Mass Index (BMI) ? 45 kg/m2 at Visit 1 (screening)
6. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation.

1.Diagnóstico de diabetes mellitus de tipo 2 previo al consentimiento informado.
2.Pacientes varones y mujeres que sigan un régimen de dieta y ejercicio y que sean naive, definido como la ausencia de cualquier tratamiento antidiabético oral, análogo de la GLP-1 o insulina durante las 12 semanas previas a la aleatorización.
3.HbA1c
a.? 7,0% y ? 10% (? 53,0 mmol/mol ? 85,8 mmol/mol) en la visita 1 (selección) para ser considerado apto para el tratamiento aleatorizado.
b.> 10,0% (> 85,5 mmol/mol) en la visita 1 (selección) para ser considerado apto para participar en el grupo abierto.
4.Edad ? 18
5.Índice de masa corporal (IMC) ? 45 kg/m2 en la visita 1 (selección)
6.Consentimiento informado firmado y fechado para el día de la visita 1 conforme a las BPC y a la legislación local.

E.4

Principal exclusion criteria

1. Uncontrolled hyperglycemia 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. Any antidiabetic drug within 12 weeks prior to randomization
3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to informed consent
4. 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 period
5. Impaired renal function, defined as estimated creatinine clearance rate (eCCr) <60 ml/min (Cockcroft-Gault formula) as determined during screening and/or run-in period
6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
8. Known blood dyscrasias or any disorders causing hemolysis or unstable red blood cell (e.g. malaria, babesiosis, hemolytic anemia)
9. Contraindications to metformin according to the local label
10. Treatment with anti-obesity drugs within 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
11. 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.
12. 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, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomized partner
13. 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
14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial
15. Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial in the opinion of the investigator

1.Hiperglucemia no controlada con una concentración de glucosa > 240 mg/dl (> 13,3 mmol/l) después de una noche de ayuno durante el periodo de preinclusión con placebo y confirmada en una segunda determinación (realizada un día diferente).
2.Uso de cualquier otro antidiabético en las 12 semanas antes de la aleatorización.
3.Síndrome coronario agudo (no-STEMI, STEMI y angina de pecho inestable), ictus o accidente isquémico transitorio (AIT) en los 3 meses anteriores a la firma del consentimiento informado.
4.Indicios de hepatopatía, definida por una concentración sérica de ALAT (SGPT), ASAT (SGOT) o de fosfatasa alcalina superiores a 3 veces el límite superior normal (LSN), según la determinación realizada durante la fase de selección y/o de preinclusión.
5.Insuficiencia renal, definida como un valor de la tasa de aclaramiento de la creatinina estimada (ClCre < 60 ml/min, según la determinación realizada durante la fase de selección y/o de preinclusión mediante la fórmula de Cockcroft-Gault.
6.Cirugía bariátrica en los dos últimos años y otras cirugías gastrointestinales que induzcan a una malabsorción crónica.
7.Antecedentes médicos de cáncer (excepto carcinoma de células basales) y/o tratamiento para el cáncer en los últimos cinco años.
8.Discrasias sanguíneas conocidas o cualquier trastorno que cause hemólisis o conduzca a eritrocitos inestables (p. ej., malaria, babesiosis, anemia hemolítica).
9.Contraindicaciones a la metformina conforme a la ficha técnica local.
10.Tratamientos con fármacos contra la obesidad en los tres meses antes del consentimiento informado o cualquier otro tratamiento en el momento de la selección (es decir, intervención quirúrgica, régimen dietético agresivo, etc.) que conduzcan a un peso corporal inestable.
11.Tratamiento actual con esteroides sistémicos en el momento del consentimiento informado o cambio en la dosificación de hormonas tiroideas en las seis semanas anteriores al consentimiento informado o cualquier otro trastorno endocrino no controlado con excepción de la DMT2.
12.Mujeres premenopáusicas (última menstruación ? 1 año antes del consentimiento informado) que:
- estén en periodo de lactancia o embarazadas, o
- sean fértiles y no utilicen un método anticonceptivo fiable o no tengan previsto seguir utilizándolo durante todo el estudio y no estén de acuerdo en someterse a pruebas de embarazo periódicas durante su participación en este estudio. Los métodos anticonceptivos seguros son por ejemplo, la ligadura de trompas, los parches transdérmicos, los dispositivos o sistemas intrauterinos (DIU o SIU), los anticonceptivos orales, implantables o inyectables, la abstinencia sexual total (si se acepta por parte de las autoridades locales), los métodos de doble barrera y la vasectomía de la pareja.
13. Alcoholismo o drogadicción en los tres meses anteriores al consentimiento informado que pudieran interferir con la participación en el estudio o cualquier afección en curso que conduzca a una disminución del cumplimiento de los procedimientos del estudio o de la toma del fármaco en estudio.
14. Ingesta de un fármaco en fase de investigación en otro ensayo en los 30 días previos a recibir la medicación de este estudio.
15. Cualquier otra condición clínica que pudiera poner en peligro la seguridad del paciente mientras participe en este estudio clínico, a criterio del investigador.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint in this study is the change from baseline in HbA1c after 24 weeks of treatment.

El criterio de valoración primario en este estudio es el cambio con respecto al nivel basal de la HbA1c en la semana 24 de tratamiento.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

24 semanas

E.5.2

Secondary end point(s)

1. Change from baseline in fasting plasma glucose (FPG) after 24 weeks of treatment
2. Change from baseline in body weight after 24 weeks of treatment

1. Cambio de la GPA (gluscosa plasmática en ayunas) en la semana 24 de tratamiento con respecto al valor basal
2. Cambio en el peso corporal en la semana 24 de tratamiento con respecto al valor basal.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks

24 semanas

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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

Yes

E.8.1.7.1

Other trial design description

Un grupo abierto

One open-label arm

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

Yes

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

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

Brazil

Canada

Czech Republic

Egypt

France

Germany

Guatemala

Hungary

India

Indonesia

Korea, Republic of

Lebanon

Malaysia

Mexico

Peru

Philippines

Russian Federation

Serbia

Spain

Taiwan

Turkey

Ukraine

United Arab Emirates

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

LVLS

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:

1140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

284

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

335

F.4.2

For a multinational trial

F.4.2.1

In the EEA

335

F.4.2.2

In the whole clinical trial

1424

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)

Patients will continue with standard of care

Los pacientes seguirán con el tratamiento estándar.

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

2012-08-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-02

P. End of Trial
P.	End of Trial Status	Completed

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