Clinical Trials Register

Summary
EudraCT Number:	2015-002619-14
Sponsor's Protocol Code Number:	1199.36
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:	2021-06-04
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

2015-002619-14

A.3

Full title of the trial

INSTAGE(TM):A 24-week, double-blind, randomized, parallel-group study evaluating the efficacy and safety of oral nintedanib coadministrated with oral sildenafil, compared to treatment with nintedanib alone, in patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment

INSTAGE(TM):Studio di 24 settimane in doppio cieco, randomizzato, a gruppi paralleli volto a valutare l'efficacia e la sicurezza di nintedanib per via orale somministrato in associazione a sildenafil per via orale rispetto al trattamento con nintedanib in monoterapia in pazienti affetti da fibrosi polmonare idiopatica (FPI) con compromissione avanzata della funzione polmonare

A.3.1

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

Efficacy and safety of nintedanib when co-administered with sildenafil in IPF patients with advanced lung function impairment

Efficacia e sicurezza di nintedanib associato a sidenafil in pazienti affetti da fibrosi polmonare idiopatica (FPI) con compromissione avanzata della funzione polmonare

A.3.2

Name or abbreviated title of the trial where available

INSTAGE(TM)

A.4.1

Sponsor's protocol code number

1199.36

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 ITALIA S.P.A.
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 Spa
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
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@boehringeringelheim.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	Yes
D.2.1.1.1	Trade name	Ofev
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim International GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1123
D.3 Description of the IMP
D.3.1	Product name	Ofev 100 mg capsule
D.3.2	Product code	nintedanib
D.3.4	Pharmaceutical form	Capsule, soft
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	Nintedanib
D.3.9.1	CAS number	656247-17-5
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB120728
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	100
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.2.1.1.1	Trade name	Ofev
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim International GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1123
D.3 Description of the IMP
D.3.1	Product name	Ofev 150 mg capsule
D.3.2	Product code	nintedanib
D.3.4	Pharmaceutical form	Capsule, soft
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	Nintedanib
D.3.9.1	CAS number	656247-17-5
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB120728
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	150
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	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	Yes
D.2.1.1.1	Trade name	Revatio
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Revatio 20 mg
D.3.2	Product code	sildenafil
D.3.4	Pharmaceutical form	Capsule, hard
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	SILDENAFIL
D.3.9.1	CAS number	139755-83-2
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB10517MIG
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	20
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Capsule, hard
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

patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment

pazienti affetti da fibrosi polmonare idiopatica (FPI) con compromissione avanzata della funzione polmonare

E.1.1.1

Medical condition in easily understood language

Idiopathic pulmonary fibrosis

fibrosi polmonare idiopatica

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10021240
E.1.2	Term	Idiopathic pulmonary fibrosis
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in IPF patients with advanced lung function impairment.

valutare efficacia e sicurezza del trattamento in associazione con nintedanib e sildenafil in pazienti affetti da fibrosi polmonare idiopatica (FPI) con compromissione avanzata della funzione polmonare

E.2.2

Secondary objectives of the trial

To enlarge the existing nintedanib mono-therapy database with safety and tolerability data in this population.

Aumentare le informazioni su nintedanib in monoterapia a disposizione con i dati di sicurezza e tollerabilità di questa popolazione.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent consistent with ICH-GCP and local laws, signed prior to any study procedures being performed (including any required washout);
2. Male or female patients aged>=40 years at visit 1;
3. A clinical diagnosis of IPF within the last 6 years before visit 1, based upon the ATS/ERS/JRS/ALAT 2011 guideline;
4. Combination of high-resolution computed tomography (HRCT) pattern, and if available, surgical lung biopsy pattern consistent with a diagnosis of IPF as assessed by the investigator based on a HRCT scan performed within 18 months of visit 1;
5. DLCO (corrected for Hb) <= 35% predicted of normal at visit 1.

1.Consenso informato scritto in accordo alle linee guida di buona pratica clinica ICH-GCP ed alle leggi locali, firmato prima che sia eseguita qualsiasi procedura dello studio (compresa qualsiasi sospensione di trattamento richiesta);
2.Pazienti di sesso maschile o femminile di età = 40 anni alla Visita 1;
3.Diagnosi clinica di fibrosi polmonare idiopatica (FPI) entro gli ultimi 6 anni prima della Visita 1, in base alle linee guida ATS/ERS/JRS/ALAT 2011;
4.La combinazione di un pattern radiologico (ottenuto mediante tomografia computerizzata ad alta risoluzione, o HRCT) e se disponibile di un pattern bioptico (ottenuto mediante biopsia chirurgica del polmone) consistenti con una diagnosi di FPI (vedi appendice 10.1) secondo valutazione dello Sperimentatore sulla base di una HRCT eseguita entro 18 mesi dalla Visita 1;
5.DLCO (corretta per l’emoglobina) = 35% del valore previsto di normalità alla Visita 1.

E.4

Principal exclusion criteria

1. Previous enrolment in this trial;
2. ALT, AST > 1.5 fold upper limit of normal (ULN) at visit 1;
3. Total bilirubin > 1.5 fold ULN at visit 1;
4. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7 at visit 1);
5. History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1;
6. Bleeding Risk: - Known genetic predisposition to bleeding; - Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin, etc.) or high dose antiplatelet therapy; - History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1; - History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1; - International normalised ratio (INR) > 2 at visit 1; - Prothrombin time (PT) and activated partial thromboplastin time (aPTT) > 150% of institutional ULN at visit 1;
7. Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;
8. History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1;
9. Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula at visit 1;
10. Presence of aortic stenosis (AS) per investigator judgement at visit 1;
11. Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25% per investigator judgement at visit 1;
12. Presence of idiopathic hypertrophic subaortic stenosis (IHSS) per investigator judgement at visit 1; 13. Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG) per investigator judgement at visit 1;
14. Hypotension (systolic blood pressure [SBP] < 100 mm Hg or diastolic blood pressure [DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1;
15. Uncontrolled systemic hypertension (SBP > 180 mmHg o DBP > 100 mmHg) at visit 1;
16. Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose to priapism;
17. Retinitis pigmentosa;
18. History of vision loss;
19. History of nonarteritic ischemic optic neuropathy;
20. Veno-occlusive disease;
21. History of acute IPF exacerbation or respiratory infection within 8 weeks of visit 2.
22. Treatment with nitrates, n-acetylcysteine, pirfenidone, azathioprine, cyclophosphamide, cyclosporine, prednisone >15 mg daily or >30 mg every 2 days OR equivalent dose of other oral corticosteroids as well as any investigational drug within 4 weeks of visit 2;
23. Treatment with prostaglandins (e.g., epoprostenol, treprostinil), endothelin-1 antagonists (e.g., bosentan, sitaxsentan, ambrisentan), phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) or a stimulator of guanylatcyclase (e.g., riociguat) within 4 weeks of visit 2;
24. Treatment with potent CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir within 4 weeks of visit 2;
25. Supplementation with L-arginine and concurrent use of grapefruit juice or St John's wort within 4 weeks of visit 2;
26. Treatment with the reduced dose of nintedanib (100 mg bid) within 4 weeks of visit 2;
27. Permanent discontinuation of nintedanib in the past due to adverse events considered drug-related;
28. Known hypersensitivity or intolerance to nintedanib, sildenafil, galactose, peanut or soya or any other components of the study medication;
29. A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial;
30. Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment;
31. Women who are pregnant, nursing, or who plan to become pregnant while in the trial;
Further exclusion criteria apply

1.Precedente arruolamento in questo studio;
2.ALT, AST > 1.5 volte il limite superiore di normalità (ULN) alla Visita 1;
3.Bilirubina totale > 1.5 volte il limite superiore di normalità (ULN) alla Visita 11;
4.Rilevante ostruzione delle vie aeree (ovvero FEV1/FVC pre-broncodilatatore < 0.7 alla Visita 1);
5.Anamnesi di infarto del miocardio entro 6 mesi dalla Visita 1 o di angina instabile entro 1 mese della Visita 1;
6.Rischio di sanguinamento (per le specifiche rifarsi alla sinossi)
7.Chirurgia maggiore programmata durante la partecipazione allo studio, compresi trapianto di polmone, chirurgia maggiore addominale o intestinale;
8.Anamnesi di evento trombotico (compreso ictus ed attacco ischemico transitorio) entro 12 mesi dalla Visita 1;
9.Clearance della creatinina < 30 mL/min calcolata mediante formula di Cockcroft-Gault (appendice 10.2) alla Visita 1;
10.Presenza di stenosi aortica (AS) secondo giudizio dello Sperimentatore alla Visita 1;
11.Insufficienza cardiaca cronica grave definita mediante frazione di eiezione ventricolare sinistra (EF) < 25% secondo giudizio dello sperimentatore alla Visita 1;
12.Presenza di stenosi subaortica ipertrofica idiopatica (IHSS) secondo giudizio dello sperimentatore alla Visita 1;
13.Blocco atrioventricolare (AV) di secondo o terzo grado all’elettrocardiogramma (ECG) secondo giudizio dello sperimentatore alla Visita 1;
14.Ipotensione (pressione del sangue sistolica [SBP] < 100 mmHg o pressione del sangue diastolica [DBP] < 50 mmHg) (ipotensione ortostatica sintomatica) alla Visita 1;
15.Ipertensione sistemica non controllata (SBP > 180 mmHg o DBP > 100 mmHg) alla Visita 1;
16.Deformità del pene o condizioni note (ad es. anemia falciforme, mieloma multiplo, leucemia) che possano predisporre al priapismo;
17.Retinite pigmentosa;
18.Anamnesi di perdita della vista;
19.Anamnesi di neuropatia ottica ischemica non-arteritica;
20.Malattia veno-occlusiva;
21.Anamnesi di riacutizzazioni della FPI o di infezioni respiratorie entro 8 settimane dalla Visita 2;
22.Trattamento con nitrati, n-acetilcisteina, pirfenidone, azatioprina, ciclofosfamide, ciclosporina, prednisone > 15 mg al giorno o > 30 mg ogni 2 giorni OPPURE dosi equivalenti di altri corticosteroidi orali così come farmaci sperimentali entro 4 settimane dalla Visita 2;
23.Trattamento con prostaglandine (ad es. epoprostenol, treprostinil), antagonisti dell’endotelina 1 (ad es. bosentan, sitaxsentan, ambrisentan), inibitori delle fosfodiesterasi (ad es. sildenafil, tadalafil, vardenafil) o con uno stimolatore della guanilciclasi (ad es. riociguat) entro 4 settimane dalla Visita 2;
24.Trattamento con potenti inibitori del citocromo CYP3A4 come ketoconazolo, itraconazolo e ritonavir entro 4 settimane dalla Visita 2;
25.Integrazione con L-arginina ed uso concomitante di succo di pompelmo o iperico (erba di San Giovanni) entro 4 settimane dalla Visita 2;
26.Trattamento con la dose ridotta di nintedanib (100 mg due volte al giorno) entro 4 settimane dalla Visita 2;
27.Interruzione permanente di nintedanib nel passato a causa di eventi avversi considerati correlati al farmaco;
28.Ipersensibilità nota o intolleranza a nintedanib, sildenafil, galattosio, arachidi, soia o qualsiasi altro eccipiente dei farmaci dello studio;
29.Una malattia o condizione che, a giudizio dello Sperimentatore, possa interferire con le procedure dello studio o mettere il paziente a rischio durante la sua partecipazione a questo studio;
30.Abuso di alcol o droghe che, a giudizio del medico curante, possa interferire con il trattamento;
31.Donne in gravidanza, in allattamento, o che pianificano di intraprendere una gravidanza durante lo studio;
32.Donne potenzialmente fertili che non vogliano o non possano usare metodi contraccettivi altamente efficaci secondo ICH M3 (R2) che risultino in una bassa frequenza di fallimento inferiore all’1% per anno quando usati costantemente e correttamente;
33.Pazienti non in grado di capire e seguire le procedure dello studio compresa la compilazione senza aiuto dei questionari auto-somministrati;
34.Pazienti con epatopatia cronica basilare (compromissione epatica Child Pugh di classe A, B o C).

E.5 End points

E.5.1

Primary end point(s)

1: change from baseline in SGRQ total score at week 12

1) Variazione rispetto al basale del punteggio totale del St. George’s Respiratory Questionnaire (SGRQ) a 12 settimane.

E.5.1.1

Timepoint(s) of evaluation of this end point

1: at week 12

1) a 12 settimane

E.5.2

Secondary end point(s)

1:change from baseline in UCSD SOBQ at week 12
2:change from baseline in SGRQ total score at week 24
3:change from baseline in UCSD SOBQ at week 24
4:% of patients with on-treatment SAE from baseline to week 24

1)Variazione rispetto al basale della dispnea usando il University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) a 12 settimane;
2)Variazione rispetto al basale del punteggio totale del SGRQ a 24 settimane;
3)Variazione rispetto al basale della dispnea usando il UCSD SOBQ a 24 settimane;
4)Percentuale dei pazienti con eventi avversi gravi in trattamento dal basale a 24 settimane.

E.5.2.1

Timepoint(s) of evaluation of this end point

1:at week 12
2:at week 24
3:at week 24
4:from baseline to week 24

1)a 12 settimane;
2)a 24 settimane;
3)a 24 settimane;
4)dal basale a 24 settimane.

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

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

Yes

E.6.13.1

Other scope of the trial description

Biomarkers

Biomarker

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

Information not present in EudraCT

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

Australia

Canada

China

India

Japan

Korea, Republic of

Mexico

United States

Belgium

France

Germany

Italy

Spain

United Kingdom

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.1.1.1

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

150

F.4.2.2

In the whole clinical trial

300

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 be treated according to clinical practice

I pazienti saranno trattati in accordo alla pratica clinica

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

2016-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-04-13

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Select Date Range: to
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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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