Clinical Trials Register

Summary
EudraCT Number:	2012-002271-34
Sponsor's Protocol Code Number:	1275.10
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-11-06
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-002271-34

A.3

Full title of the trial

A phase III, randomized, double-blind, parallel group study to evaluate the efficacy and safety of linagliptin 5 mg compared to placebo, administered as oral fixed dose combination with empagliflozin 10 mg or 25 mg, in patients with type 2 diabetes mellitus and insufficient glycaemic control after 16 weeks of treatment with empagliflozin 10 mg or 25 mg on metformin background therapy.

Studio clinico di fase III, randomizzato, in doppio cieco, a gruppi paralleli ,volto a valutare l'efficacia e la sicurezza di linagliptin 5 mg in confronto a placebo, somministrato oralmente con empagliflozin 10 mg o 25 mg in associazione a dose fissa per un periodo di 24 settimane, in pazienti con diabete mellito di tipo 2 che mostrano insufficiente controllo glicemico dopo un trattamento di 16 settimane con empagliflozin 10 mg o 25 mg e terapia di base con metformina.

A.3.1

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

A study to evaluate the effect and safety of linagliptin 5 mg administered in combination with empagliflozin 10 mg or 25 mg in patients with type 2 diabetes mellitus whose glucose levels have not been controlled after 16 weeks of treatment with empagliflozin 10 mg or 25 mg and metformin.

Studio volto a valutare l'efficacia e la sicurezza di linagliptin 5 mg, somministrato con empagliflozin 10 mg o 25 mg, in pazienti con diabete mellito di tipo 2 che mostrano insufficiente controllo glicemico dopo un trattamento di 16 settimane con empagliflozin 10 mg o 25 mg e metformina

A.4.1

Sponsor's protocol code number

1275.10

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 ING.
B.1.3.4	Country	Italy
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 Italia s.p.a.
B.4.2	Country	Italy
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	001 800 243 0127
B.5.5	Fax number	001 800 921 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 + Linagliptin
D.3.2	Product code	BI 10773 + BI 1356
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.3.9.4	EV Substance Code	SUB35915
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LINAGLIPTIN
D.3.9.2	Current sponsor code	BI 1356
D.3.9.4	EV Substance Code	SUB31340
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: 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 + Linagliptin
D.3.2	Product code	BI 10773 + BI 1356
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.3.9.4	EV Substance Code	SUB35915
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LINAGLIPTIN
D.3.9.2	Current sponsor code	BI 1356
D.3.9.4	EV Substance Code	SUB31340
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.3.9.3	Other descriptive name	Empagliflozin
D.3.9.4	EV Substance Code	SUB35915
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.3.9.3	Other descriptive name	Empagliflozin
D.3.9.4	EV Substance Code	SUB35915
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.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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetes mellitus type 2

Diabete mellito di tipo 2

E.1.1.1

Medical condition in easily understood language

Diabetes mellitus type 2

Diabete mellito di tipo 2

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	100000004861

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, safety and tolerability of linagliptin 5 mg qd compared to placebo given for 24 weeks in inadequately controlled T2DM patients on empagliflozin 10 mg or 25 mg and maximum tolerated dose of metformin. The study is designed to show superiority of the combination of empagliflozin and linagliptin over empagliflozin alone.

L'obiettivo dello studio e' valutare l'efficacia, la sicurezza e la tollerabilita' di linagliptin 5 mg somministrato per 24 settimane in confronto a placebo in pazienti con diabete mellito di tipo 2 non controllati adeguatamente dopo 16 settimane di trattamento con empagliflozin 10 mg o 25 mg in aggiunta alla massima dose tollerata di metformina. Il disegno dello studio e' mirato alla dimostrazione di superiorita' della combinazione di empagliflozin e linagliptin rispetto a solo empagliflozin.

E.2.2

Secondary objectives of the trial

Fasting plasma glucose (FPG) change from baseline (Visit 5) at 24 weeks (or Visit 9)

variazione di glucosio plasmatico a digiuno (FPG) rispetto al basale (visita 5) a 24 settimane (o visita 9)

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 and who are pre-treated with an unchanged dose of immediate release metformin for at least 12 weeks prior to Visit 2. Minimum dose for metformin is defined as: - >=1500 mg/day of metformin or - maximum tolerated dose (the investigator must have documented the reason why uptitration to e.g. >= 1500 mg/day was not possible) or - maximum dose according to the local label (the investigator must have documented the local label requirements in the medical records) Note: Medical records supporting metformin start date and dosage must be available. 3. HbA1c >= 8.0% (64 mmol/mol) and <= 10.5% (91 mmol/mol) at Visit 1 for randomization into the 16 week treatment period. 4. HbA1c >= 7.0% (53 mmol/mol) and <= 10.5 % (91 mmol/mol) at Visit 4 for randomization into the 24 week treatment period. 5. Age >= 18 years 6. Body Mass Index (BMI) <=45 kg/m2 at Visit 1 (screening) as calculated in the eCRF. 7. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation

1.Diagnosi di diabete mellito di tipo 2 prima della firma del consenso informato 2.Pazienti maschi e femmine in regime dietetico e di esercizio fisico e che sono in trattamento con una dose di metformina a rilascio immediato a dosaggio invariato da almeno 12 settimane prima di visita 2. La dose minima di metformina e' definita come: - >= 1500 mg/dì di metformina o - dose massima tollerata (lo sperimentatore deve documentare il motivo che ha portato all'impossibilita' dell'incremento del dosaggio >= 1500 mg/dì) o -dose massima in accordo al foglietto informativo (lo sperimentatore deve aver documentato i requisiti del foglietto locale in cartella clinica) Nota: Le cartelle cliniche che riportano la data di inizio trattamento con metformina e il dosaggio devono essere disponibili. 3.HbA1c >= 8.0% (64 mmol/mol) e <= 10.5% (91 mmol/mol) alla visita 1 per il periodo di 16 settimane di trattamento in aperto. 4.HbA1c >= 7.0% (53 mmol/mol) e <= 10 % (86 mmol/mol) alla visita 4 per il periodo di 24 settimane di trattamento doppio cieco. 5.Eta' >= 18 anni 6.Body Mass Index (BMI) <=45 kg/m2 alla visita 1 (screening) e calcolata in eCRF. 7.Consenso informato scritto, firmato e datato entro la data della visita 1, in accordo con le GCP e la legislazione nazionale.

E.4

Principal exclusion criteria

1. Uncontrolled hyperglycaemia with a glucose level >270 mg/dl (>15.0 mmol/L) after an overnight fast during the open label period (from Visit 2 to Visit 4) and placebo add on ''run-in'' period (Visit 4 to Visit 5) and confirmed by a second measurement (not on the same day and done either at the central or local laboratory). 2. Any other antidiabetic drug within 12 weeks prior to Visit 2 randomization (except metformin background therapy as defined via inclusion criterion 2). 3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or 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) based on Visit 1 and Visit 4 laboratory parameters. 5. Impaired renal function, defined as eGFR <60 ml/min/1.73 m2 (MDRD formula) as determined during screening (Visit 1) or placebo add on ''run-in'' (Visit 4) 6. Known hereditary galactose intolerance 7. Known contraindications to metformin or linagliptin according to the local label (where marketed) 8. Any previous (within the past two years) or planned bariatric surgery (or any other weight loss surgery) or other gastrointestinal surgery that induce chronic malabsorption 9. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years 10. Known blood dyscrasias or any disorders causing haemolysis or unstable red blood cell count (e.g. malaria, babesiosis, haemolytic anaemia) due to the short lifespan of the RBC and its impact on HbA1c. 11. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 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 12. Current treatment with systemic steroids (other than inhaled or topical steroids) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other documented uncontrolled endocrine disorder except T2DM 13. 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 trial 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 health authorities), double barrier method and vasectomised partner 14. Known allergy or hypersensitivity to DPP4 inhibitors or SGLT-2 inhibitors 15. 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 trial procedures or trial drug intake, in the judgment of the investigator 16. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participation in the follow-up period of another trial (participation in observational studies is permitted). 17. Any other clinical condition that, in the opinion of the investigator, would jeopardize patient's safety while participating in this clinical trial.

1.Iperglicemia non controllata con un livello di glicemia> 270 mg / dl (> 15,0 mmol / L) dopo il digiuno notturno durante il periodo in aperto (da visita 2 a visita 4) e dopo il periodo di ''run-in'' con placebo (da visita 4 a visita 5) e confermato da una seconda misurazione (non lo stesso giorno ed eseguita dal laboratorio centrale o locale). 2.Qualunque altro farmaco antidiabetico preso nelle 12 settimane prima della randomizzazione (eccetto metformina come terapia di background, come definito nel criterio di inclusione 2). 3.Sindrome coronarica acuta (non-STEMI, STEMI e angina pectoris instabile), ictus o TIA nei 3 mesi precedenti al consenso informato 4.Indicazione di malattia epatica, definita da livelli sierici di ALT (SGPT) e AST (SGOT), o della fosfatasi alcalina, superiori a 3 volte il limite superiore della norma (ULN) sulla base di parametri di laboratorio a visita 1 e visita 4. 5.Compromissione della funzionalita' renale, definita come eGFR <60 ml/min/1.73 m2 (MDRD) come determinato durante lo screening (visita 1) o il periodo di ''run-in'' con placebo (visita 4) 6.Intolleranza ereditaria al galattosio. 7.Controindicazioni note alla metformina o linagliptin secondo il foglietto informativo locale (se commercializzato). 8.Chirurgia per il controllo ponderale entro i due anni precedenti ed altri interventi gastrointestinali che inducono malassorbimento cronico. 9.Storia medica di cancro (eccetto carcinoma delle cellule basali) e/o trattamento per cancro negli ultimi 5 anni. 10.Discrasie od altri disturbi che causino emolisi e emivita breve/instabile degli eritrociti (es. malaria, babesiosi, anemia emolitica) a causa della breve durata di vita dell'RBC e il suo impatto sulla HbA1c. 11.Trattamento con farmaci anti-obesita' entro 3 mesi prima del consenso informato o qualunque altro trattamento al momento dello screening (cioè chirurgia, regime dietetico aggressivo, ecc...) che porti ad instabilita' ponderale. 12.Trattamento corrente con steroidi sistemici al momento del consenso informato o modifiche di dosaggio negli ormoni tiroidei entro le 6 settimane precedenti il consenso informato o qualunque altro disturbo endocrino (tranne il T2DM). 13.Donne in pre-menopausa (ultima mestruazione <=1 anno prima del CI) che: a.Siano in allattamento o in gravidanza; b.Siano in eta' fertile e non usino un metodo contraccettivo accettabile dal punto di vista medico o che non intendano usarlo per tutta la durata dello studio e che non accettino di eseguire periodicamente un test di gravidanza durante lo studio. Metodi accettabili di contraccezione includono: legamento delle tube, cerotto transdermico, dispositivi intrauterini (IUD/IUS), contraccettivi orali, impiantabili o iniettabili, astinenza sessuale completa (se accettabile dalle Autorita' Sanitarie Nazionali), metodo a doppia barriera e partner vasectomizzato. 14.Allergia o ipersensibilità agli inibitori DPP4 o SGLT-2 15.Abuso di alcol o sostanze stupefacenti entro i 3 mesi prima del consenso informato che possa interferire con la partecipazione allo studio o qualunque condizione presente che possa abbassare la compliance del paziente alle procedure dello studio o all'assunzione del farmaco, a giudizio dello sperimentatore. 16.L'assunzione di un farmaco sperimentale in un altro studio clinico, entro 30 giorni dalla prima assunzione del farmaco per il presente studio e/o la partecipazione ad un follow-up per un altro studio (la partecipazione a studi osservazionali e' permessa). 17.Qualunque altra condizione medica che, a giudizio dello sperimentatore metterebbe a rischio la sicurezza del paziente mentre partecipa allo studio.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change of HbA1c after 24 weeks of treatment (at week 24 or Visit 9) from baseline (Visit 5).

L'endpoint primario di questo studio e' la variazione di HbA1c dopo 24 settimane di trattamento (alla settimana 24 o visita 9) rispetto al basale (visita 5). HbA1c sara' misurata in unita' di % e mmol / mol a tutte le visite cliniche.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 24 weeks of treatment (Visit 9) from baseline (Visit 5).

alla settimana 24 o visita 9 rispetto al basale (visita 5).

E.5.2

Secondary end point(s)

Fasting plasma glucose (FPG) change from baseline (Visit 5) at 24 weeks (or Visit 9)

Endpoint chiave secondario e' la variazione di glucosio plasmatico a digiuno (FPG) rispetto al basale (visita 5) a 24 settimane (o visita 9).

E.5.2.1

Timepoint(s) of evaluation of this end point

After 24 weeks of treatment (Visit 9) from baseline (Visit 5).

alla settimana 24 o visita 9 rispetto al basale (visita 5).

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

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

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

Canada

India

Peru

Russian Federation

Sri Lanka

Ukraine

United States

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

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

Number of subjects for this age range:

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:

1383

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

460

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

175

F.4.2

For a multinational trial

F.4.2.1

In the EEA

570

F.4.2.2

In the whole clinical trial

1843

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)

none

nessuno

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

2013-02-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-30

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

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Orphan Designation Number:
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