Clinical Trials Register

Summary
EudraCT Number:	2014-001579-30
Sponsor's Protocol Code Number:	TV5600-CNS-20006
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:	2014-09-19
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

2014-001579-30

A.3

Full title of the trial

A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Once Daily Oral Administration of Laquinimod (0.6 or 1.5 mg) in Patients with Primary Progressive Multiple Sclerosis (PPMS)

Studio multinazionale, multicentrico, randomizzato, in doppio cieco, a gruppi paralleli, controllato con placebo per valutare l'efficacia, la sicurezza e la tollerabilità della somministrazione per via orale una volta al giorno di Laquinimod (0,6 o 1,5 mg) in pazienti affetti da sclerosi multipla primaria progressiva (SMPP)

A.3.1

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

A Phase 2 clinical study in subjects with Progressive Multiple Sclerosis to assess the efficacy, safety and tolerability of two oral doses of laquinimod either of 0.6 mg/day or 1.5mg/day (experimental drug) as
compared to placebo

Studio clinico di Fase 2 in soggetti con sclerosi multipla progressiva per valutare l’efficacia, la sicurezza e la tollerabilità della somministrazione per via orale di due dosi di laquinimod da 0,6 mg/die o 1,5 mg/die (farmaco sperimentale) quando messo a confronto con placebo

A.3.2

Name or abbreviated title of the trial where available

ARPEGGIO

A.4.1

Sponsor's protocol code number

TV5600-CNS-20006

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	Teva Pharmaceutical Industries Ltd.
B.1.3.4	Country	Israel
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	Teva Pharmaceutical Industries Ltd
B.4.2	Country	Israel
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Teva Pharma GmbH
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Waldeckerstrasse 7
B.5.3.2	Town/ city	Moerfelden-Walldorf
B.5.3.3	Post code	64546
B.5.3.4	Country	Germany
B.5.4	Telephone number	000000000000
B.5.5	Fax number	000000000000
B.5.6	E-mail	Info-era-clinical@teva.de

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	Laquinimod
D.3.2	Product code	TV-5600
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	LAQUINIMOD
D.3.9.1	CAS number	248282-07-7
D.3.9.2	Current sponsor code	TV-5600
D.3.9.3	Other descriptive name	Laquinimod Sodium (USAN)
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	0.6
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	Laquinimod
D.3.2	Product code	TV-5600
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	LAQUINIMOD
D.3.9.1	CAS number	248282-07-7
D.3.9.2	Current sponsor code	TV-5600
D.3.9.3	Other descriptive name	Laquinimod Sodium (USAN)
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	0.5
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.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

Primary Progressive Multiple Sclerosis

Sclerosi multipla primaria progressiva

E.1.1.1

Medical condition in easily understood language

Primary Progressive Multiple Sclerosis (PPMS) is an autoimmune disease of the central nervous system featuring gradual worsening of neurological function without distinct exacerbations.

La sclerosi multipla primaria progressiva (SMPP) è una malattia autoimmune del sistema nervoso centrale con progressivo peggioramento della funzione neurologica, senza esacerbazioni distinte.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10063401
E.1.2	Term	Primary progressive multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system 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 objectives of this study are to assess the efficacy, safety, and tolerability of a once daily oral dose
of laquinimod (0.6 or 1.5 mg) compared to placebo in PPMS patients.

gli obiettivi di questo studio sono le valutazioni di efficacia, sicurezza e tollerabilità della dose orale giornaliera di laquinimod una volta al giorno (0,6 o 1,5 mg) rispetto al placebo nei pazienti con SMPP.

E.2.2

Secondary objectives of the trial

Not applicable

Non applicabile

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Sub-studies (Ancillary studies) are described within the current core study protocol.
Some of these studies may be performed only in selected sites and in accordance with local regulations as applicable.

1. Pharmacokinetc Variables: Pharmacokinetics of laquinimod will be evaluated
2. Potential Biomarker Measures: Potential biomarker assessments to better understand laquinimod MoA, as well as to explore response predictive markers for efficacy or safety
3.Pharmacogenomic Variables: PGx analyses to investigate the association between genetic sequence polymorphisms and/or gene and clinical response including unexpected adverse events.
4. Cerebrospinal fluid (CSF) assessment: to explore putative neuroprotective effects of laquinimod
5. Optical coherence tomography (OCT) assessment: used as a tool for visualizing the processes of
neurodegeneration, neuroprotection, and neurorepair in MS.

I sottostudi (studi ancillari) sono descritti all’interno dell’attuale protocollo dello studio principale.
Alcuni di questi studi possono essere effettuati solo presso centri selezionati e in conformità alle normative locali, ove applicabile.

1. Variabili farmacocinetiche: Sarà valutata la farmacocinetica di laquinimod
2. Parametri dei biomarcatori potenziali: Valutazioni dei biomarcatori potenziali per comprendere meglio il meccanismo di azione di laquinimod, nonché per esplorare i marcatori predittivi della risposta per l’efficacia o la sicurezza
3. Variabili farmacogenomiche: Analisi PGx per valutare l’associazione tra polimorfismi genetici di sequenza e/o i geni e la risposta clinica compresi gli eventi avversi inattesi.
4. Valutazione del liquido cerebrospinale (Cerebrospinal fluid, CSF): per esplorare gli effetti neuroprotettivi putativi di laquinimod
5. Valutazione della tomografia a coerenza ottica (Optical coherence tomography, OCT): utilizzato come strumento per la visualizzazione dei processi di neurodegenerazione, neuroprotezione e neuroriparazione nella SM.

E.3

Principal inclusion criteria

1. Patients must have a confirmed and documented PPMS diagnosis as defined by the current valid McDonald criteria
2. Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in either or both brain and spinal cord
3. Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5, inclusive, at both
screening and baseline visits
4. Documented evidence of clinical disability progression in the 2 years prior to screening.
5. Functional System Score (FSS) of > or equal 2 for the pyramidal system or gait impairment due to lower extremity dysfunction
6. Patients must be between 25 to 55 years of age, inclusive
7. Women of child-bearing potential must practice an acceptable method of birth control for 30 days before taking the study drug, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment is administered.
8. Patients must sign and date a written informed consent prior to entering the study.
9. Patients must be willing and able to comply with the protocol requirements for the duration of the study.

1.I pazienti devono presentare una diagnosi confermata e documentata di SMPP in base alla definizione dei criteri McDonald rivisti del 2010.
2.Risonanza magnetica per immagini (RMI) al basale che mostri lesioni riferibili a SMPP a livello cerebrale e/o del midollo osseo.
3.I pazienti devono presentare un punteggio compreso tra 3 e 6,5 (inclusi) nella scala di invalidità espansa (Expanded Disability Status Scale, EDSS) sia alla visita di screening sia alla visita basale.
4.Evidenza documentata di progressione di invalidità clinica nei 2 anni precedenti lo screening.
5.Punteggio funzionale di sistema (Functional System Score, FSS) di 2 per il sistema piramidale o disturbo della deambulazione dovuti a una disfunzione degli arti inferiori.
6.I pazienti devono avere un’età compresa tra i 25 e i 55 anni, inclusi.
7.Le donne potenzialmente fertili devono utilizzare un metodo accettabile di controllo delle nascite 30 giorni prima di assumere il farmaco in studio e 2 metodi accettabili di controllo delle nascite per tutta la durata dello studio e fino a 30 giorni dopo la somministrazione dell’ultima dose del trattamento.
8.I pazienti devono firmare e datare un modulo di consenso informato scritto prima di accedere allo studio.
9.I pazienti devono essere disposti e in grado di attenersi ai requisiti previsti dal protocollo per tutta la durata dello studio.

E.4

Principal exclusion criteria

1. Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis.
2. Progressive neurological disorder other than PPMS.
3. Any MRI record showing presence of cervical cord compression.
4. Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms.
5. Relevant history of vitamin B12 deficiency.
6. Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.
7. Use of experimental or investigational drugs in a clinical study within 24 weeks prior to baseline. Use of a currently marketed drug in a clinical study within 24 weeks prior to baseline would not be exclusionary, provided no other exclusion criteria are met.
8. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine
within 48 weeks prior to baseline.
9. Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate (TECFIDERA®, Biogen
Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-β (either 1a or 1b), intravenous
immunoglobulin, or plasmapheresis within 8 weeks prior to baseline.
10. Use of teriflunomide (AUBAGIO®, Sanofi) within 2 years prior to baseline, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to baseline.
11. Prior use of monoclonal antibodies ever, except for:
a. natalizumab (TYSABRI®, Biogen Idec Inc), if given more than 24 weeks prior to baseline AND the
patient is John Cunningham (JC) virus antibody test negative (as per medical history)
b. rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than
80 cells/μL
12. Use of mitoxantrone (NOVANTRONE®, Immunex) within 5 years prior to screening. Use of mitoxantrone >5 years before screening is allowed in patients with normal ejection fraction and who did not exceed the total lifetime maximal dose.
13. Previous use of laquinimod.
14. Chronic (eg, more than 30 consecutive days or monthly dosing, with the intent of MS disease modification) systemic (intravenous, intramuscular or oral) corticosteroid treatment within 8 weeks prior to baseline.
15. Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi).
16. Previous total body irradiation or total lymphoid irradiation.
17. Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of any kind.
18. Patients who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) within 12 weeks prior to baseline.
19. Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to baseline.
20. Use of inducers of CYP3A4 within 2 weeks prior to baseline.
21. Pregnancy or breastfeeding.
22. Serum levels ≥3× upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) at screening.
23. Serum direct bilirubin which is ≥2×ULN at screening.
24. Patients with a clinically significant or unstable medical or surgical condition that (in the opinion of the Investigator) would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests or chest X-ray.
25. A known history of hypersensitivity to gadolinium (Gd).
26. Glomerular filtration rate (GFR) < or equal 60 mL/min at screening visit.
27. Inability to successfully undergo MRI scanning, including claustrophobia.
28. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.

1.Pazienti con anamnesi di qualsiasi esacerbazione o recidiva di sclerosi multipla (SM), inclusi eventuali episodi di neurite ottica.
2.Malattia neurologica progressiva diversa dalla SMPP.
3.Qualsiasi dato di RMI che mostri la presenza di compressione del midollo spinale a livello cervicale.
4.RMI al basale che mostri altri risultati (incluse lesioni atipiche per la SMPP) che possano spiegare i segni e sintomi clinici.
5.Anamnesi relativa a carenza di vitamina B12.
6.Test sierologico positivo al virus T-linfotropico umano di tipo I e II (HTLV-I/II).
7.Uso di farmaci sperimentali o in fase di sperimentazione in uno studio clinico nelle 24 settimane prima del basale. L’uso di un farmaco attualmente disponibile in commercio nell’ambito di uno studio clinico nelle 24 settimane prima del basale non determina l’esclusione, sempre che non siano riscontrati altri criteri di esclusione.
8.Uso di agenti immunosoppressori o citotossici, incluse ciclofosfamide e azatioprina, nelle 48 settimane prima del basale.
9.Precedente trattamento con fingolimod (GILENYA®, Novartis), dimetilfumarato (TECFIDERA®, Biogen Idec Inc), glatiramer acetato (COPAXONE®, Teva), interferone β (1a o 1b), immunoglobuline per via endovenosa o plasmaferesi nelle 8 settimane prima del basale.
10.Uso di teriflunomide (AUBAGIO®, Sanofi) nei 2 anni prima del basale, fatta eccezione per il washout attivo (con colestiramina o carbone attivo) eseguito almeno 2 mesi prima del basale.
11.Pregresso impiego di anticorpi monoclonali, fatta eccezione per:
a.natalizumab (TYSABRI®, Biogen Idec Inc), se somministrato più di 24 settimane prima del basale E il paziente risulta negativo al test sugli anticorpi del virus di John Cunningham (JC) (in base all’anamnesi)
b.rituximab, ocrelizumab oppure ofatumumab, se la conta delle cellule B (CD19, in base all’anamnesi) è superiore a 80 cellule/µl
12.Uso di mitoxantrone (NOVANTRONE®, Immunex) nei 5 anni prima dello screening. L’uso di mitoxantrone più di5 anni prima dello screening è consentito nei pazienti con una normale frazione di eiezione che non hanno superato la dose totale cumulativa massima.
13.Uso pregresso di laquinimod.
14.Trattamento con corticosteroidi cronico (ad esempio per più di 30 giorni consecutivi o dosaggio mensile con intenzione di modificare la SM), sistemico (per via endovenosa, intramuscolare oppure orale) nelle 8 settimane prima del basale.
15.Pregresso uso di cladribina o alemtuzumab (LEMTRADA®, Sanofi).
16.Pregressa irradiazione totale corporea o irradiazione totale dei linfonodi.
17.Pregresso trapianto di cellule staminali, trattamento a base di cellule o trapianto di midollo osseo di qualsiasi tipo.
18.Pazienti sottoposti a trattamento endovascolare per insufficienza venosa cronica cerebrospinale (Chronic Cerebrospinal Venous Insufficiency, CCSVI) nelle 12 settimane prima del basale.
19.Uso di inibitori moderati/forti del citocromo P450 (cytochrome P450, CYP) 3A4 nelle 2 settimane prima del basale.
20.Uso di induttori del CYP3A4 nelle 2 settimane prima del basale.
21.Gravidanza o allattamento.
22.Livello sierico di alanina aminotransferasi (ALT) o aspartato aminotransferasi (AST) ≥3 volte il limite superiore della norma (Upper Limit of Normal, ULN) allo screening.
23.Livello sierico della bilirubina diretta ≥2 volte rispetto all’ULN allo screening.
24.Pazienti con una patologia medica o chirurgica clinicamente significativa o instabile che, a parere dello sperimentatore, precluderebbe una partecipazione sicura e completa allo studio, in base ad anamnesi medica, a esami obiettivi, a elettrocardiogramma (ECG), ad analisi di laboratorio o a radiografia toracica.
25.Nota anamnesi di ipersensibilità al gadolinio (Gd).
26.Tasso di filtrazione glomerulare (Glomerular Filtration Rate, GFR) 60 ml/min alla visita di screening.
27.Incapacità di sottoporsi in modo adeguato alla RMI, inclusa claustrofobia.
28.Nota ipersensibilità ai farmaci che precluderebbe la somministrazione di laquinimod, come un’ipersensibilità a mannitolo, meglumina o sodio stearil fumarato.

E.5 End points

E.5.1

Primary end point(s)

Brain atrophy (BA), defined as change in brain volume

Atrofia cerebrale (Brain Atrophy, BA), in base alla percentuale di variazione del volume cerebrale (Percentage in Brain Volume Change, PBVC)

E.5.1.1

Timepoint(s) of evaluation of this end point

Percentage in Brain Volume Change (PBVC) from baseline to week 48

Atrofia cerebrale (Brain Atrophy, BA), in base alla percentuale di variazione del volume cerebrale (Percentage in Brain Volume Change, PBVC) dal basale alla settimana 48.

E.5.2

Secondary end point(s)

-Time to CDP (confirmed disability progression) defined by an increase in baseline EDSS
-Time to CDP defined by an increase in baseline EDSS or at least a 20% worsening in the Timed 25 Foot Walk
- The number of new T2 brain lesions
-Change in the BICAMS (Cognitive Assessment for Multiple Sclerosis score)

•Tempo alla progressione dell’invalidità confermata (Confirmed Disability Progression, CDP), definita come aumento del punteggio EDSS
•Tempo alla CDP misurata tramite un aumento dal basale nel punteggio EDSS
•Tempo alla CDP misurata tramite un aumento di almeno il 20% rispetto al basale nel punteggio T25FW
•Numero di nuove lesioni cerebrali in T2
•Variazione nel punteggio BICAMS

E.5.2.1

Timepoint(s) of evaluation of this end point

-Time to confirmed disability progression (CDP), to be confirmed after at least 12 weeks
-An increase from baseline in EDSS score confirmed after at least 12 weeks
-An increase of at least 20% from baseline in T25FW score, confirmed after at least 12 weeks
-The number of new T2 brain lesions at week 48
-Change from baseline to week 48 in the BICAMS score

•Tempo alla progressione dell’invalidità confermata (Confirmed Disability Progression, CDP), deve essere confermato dopo almeno 12 settimane.
•Un aumento dal basale nel punteggio EDSS confermato dopo almeno 12 settimane
•Un aumento di almeno il 20% rispetto al basale nel punteggio T25FW, confermato dopo almeno 12 settimane
•Numero di nuove lesioni cerebrali in T2 alla settimana 48
•Variazione dal basale alla settimana 48 nel punteggio BICAMS

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Canada

Russian Federation

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.1.1.1

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:

375

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

211

F.4.2.2

In the whole clinical trial

375

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)

Standard of care treatment

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

2014-12-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-10-01

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