Clinical Trials Register

Summary
EudraCT Number:	2012-002940-26
Sponsor's Protocol Code Number:	212082PCR3011
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:	2012-10-30
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

Spain - AEMPS

A.2

EudraCT number

2012-002940-26

A.3

Full title of the trial

A Randomized, Double-blind, Comparative Study of ZYTIGA (Abiraterone Acetate) Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Subjects With High-Risk, Metastatic Hormone-naive Prostate Cancer (mHNPC)

Estudio aleatorizado, doble-ciego y comparativo de ZYTIGA® (acetato de abiraterona), más dosis bajas de prednisona, más terapia de privación de andrógenos (TPA), frente a TPA sola en sujetos con cáncer de próstata metastásico sin tratamiento hormonal previo (CPmSTHP), de nuevo diagnóstico y alto riesgo

A.3.1

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

A Study of ZYTIGA and Prednisone with Androgen Deprivation Therapy (ADT) compared to ADT Alone in men newly Diagnosed (within the previous 3 months) with High-Risk, Metastatic Prostate Cancer

Estudio de ZYTIGA y Prednisona con Terapia de privación de andrógenos (TPA) comparado con TPA sola en hombres diagnosticados recientemente (en los 3 meses previos) con un cáncer de próstata metastásico de alto riesgo.

A.4.1

Sponsor's protocol code number

212082PCR3011

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	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
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	Janssen-Cilag International, NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janseen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Janssen Biologics BV - Clinical Registry Group- Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3171524 21 66
B.5.5	Fax number	+3171524 21 10
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	ZYTIGA
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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	ZYTIGA
D.3.2	Product code	JNJ 212082
D.3.4	Pharmaceutical form	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	ABIRATERONE ACETATE
D.3.9.2	Current sponsor code	JNJ-212082
D.3.9.4	EV Substance Code	SUB31647
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	250
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	Yes
D.2.1.1.1	Trade name	Prednisone
D.2.1.1.2	Name of the Marketing Authorisation holder	Acis Arzneimittel 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.3.1	Product name	Prednisone
D.3.4	Pharmaceutical form	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	PREDNISONE
D.3.9.1	CAS number	53-03-2
D.3.9.3	Other descriptive name	PREDNISONE
D.3.9.4	EV Substance Code	SUB10020MIG
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.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	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	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

Metastatic Hormone-Naive Prostate Cancer (mHNPC)

Cáncer de próstata metastásico sin tratamiento hormonal previo (CPmSTHP)

E.1.1.1

Medical condition in easily understood language

Prostate Cancer

Cáncer de próstata

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine whether ZYTIGA in combination with low-dose prednisone and ADT is superior to ADT alone in improving survival in subjects with mHNPC with high risk prognostic factors.

El objetivo principal consiste en determinar si ZYTIGA, en combinación con prednisona a dosis bajas y TPA, y a diferencia de TPA sola, mejora el índice de supervivencia en sujetos con CPmSTHP y factores de pronóstico de alto riesgo.

E.2.2

Secondary objectives of the trial

?To evaluate the clinically relevant improvements as well as the safety of ZYTIGA plus low-dose prednisone and ADT compared to ADT alone.
?To identify microRNA (miRNA) and mRNA profiles predictive of ZYTIGA response or resistance.

- Evaluar las mejoras clínicamente relevantes, así como la seguridad de ZYTIGA más prednisona a dosis bajas y TPA, en comparación con TPA sola
- Identificar perfiles de microARN (miARN) y ARNm que puedan pronosticar la respuesta o resistencia a ZYTIGA en esta población de pacientes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
2. Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography or magnetic resonance imaging scan
3. Two of the following high-risk prognostic factors: Gleason score of >=8; presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis
4. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2
5. Adequate hematologic, hepatic, and renal function
6. Agrees to protocol-defined use of effective contraception

1. Estar dispuesto y ser capaz de proporcionar el consentimiento informado por escrito.
2. Tener 18 años o más.
3. Cáncer de próstata metastásico recién diagnosticado (3 meses o menos antes de la aleatorización) con confirmación histológica y citológica de adenocarcinoma de próstata sin diferenciación neuroendocrina o histología de células pequeñas.
4. Enfermedad metastásica distante, documentada por gammagrafía ósea positiva o detección de lesiones metastásicas por TAC o RM.
5. Dos de los siguientes factores de pronóstico de alto riesgo: Puntuación de Gleason ?8 Presencia de 3 o más lesiones en gammagrafía ósea Presencia de metástasis visceral medible (excluyendo ganglios linfáticos) (RECIST 1.1)
6.Estado funcional según la escala ECOG de 0, 1 o 2 (Anexo 1).
7. Función hematológica, hepática y renal adecuadas: hemoglobina 9,0 g/dl independiente de las transfusiones neutrófilos 1,5 x 109/L plaquetas 100 x 109/L bilirrubina total 1,5 veces el límite superior de la normalidad (LSN) [excepto para sujetos con enfermedad de Gilbert documentada, en cuyo caso la bilirrubina total no excederá 10 veces el LSN] alanina ( ALT ) y aspartato ( AST ) aminotransferasa 2,5 veces el LSN creatinina del suero <1,5 veces el LSN o aclaramiento de creatinina calculada 50 ml/min potasio en suero 3,5 mM
8. Capacidad de ingerir los comprimidos de la medicación del estudio.
9. Aceptar el uso de un preservativo u otro método anticonceptivo eficaz si mantiene relaciones sexuales con una mujer con capacidad de concebir o acepta el uso de un preservativo si mantiene relaciones sexuales con una mujer embarazada.

E.4

Principal exclusion criteria

1. Active infection or other medical condition that would make prednisone use contraindicated
2. Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day
3. Pathological finding consistent with small cell carcinoma of the prostate
3. Known brain metastasis
4. Any prior pharmacotherapy, radiation therapy, or surgery with curative intent for metastatic prostate cancer (the following exception is allowed: up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or orchiectomy with or without concurrent anti-androgens prior to patients randomization is permitted; patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered prior to randomization)
5. Radiation or surgical therapy could not have been initiated 4 weeks after the start of ADT or orchiectomy
6. Uncontrolled hypertension (systolic blood pressure >=160 mmHg or diastolic BP >=95 mmHg; patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment)
7. Active or symptomatic viral hepatitis or chronic liver disease
8. History of adrenal dysfunction
9. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline
10. Atrial fibrillation, or other cardiac arrhythmia requiring pharmacotherapy
11. Other malignancy (within 5 years), except non-melanoma skin cancer
12. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study
13. Any condition or situation which, in the opinion of the investigator, would put the patient at risk, may confound study results, or interfere with the patient?s participation in this study

1. Infección activa u otra afección médica que contraindica el uso de prednisona.
2. Cualquier afección médica crónica que requiera una dosis sistémica de corticosteroide superior a 5 mg de prednisona diarios.
3. Hallazgos patológicos que indican carcinoma de próstata de células pequeñas.
4. Metástasis cerebral conocida.
5. Cualquier farmacoterapia, radioterapia o cirujía previa destinada a curar el cáncer de próstata metastásico. Se permiten las excepciones siguientes: Se permiten hasta 3 meses de TPA con agonistas de la LHRH u orquiectomía con o sin antiandrógenos concurrentes antes de la aleatorización de los sujetos. Los sujetos pueden recibir un ciclo de radiación paliativa o terapia quirúrgica para tratar los síntomas que resulten de la enfermedad metastásica (por ejemplo: compresión inminente de la médula espinal o síntomas obstructivos) si se produjo antes de la aleatorización. La radioterapia o la terapia quirúrgica no pudo haberse iniciado 4 semanas después del comienzo de la TPA o de la orquiectomía.
6. Hipertensión no controlada (tensión arterial sistólica ?160 mmHg o TA diastólica ?95 mmHg). Se admiten sujetos con antecedentes de hipertensión, siempre que se controle la tensión arterial con tratamiento antihipertensivo.
7. Hepatitis viral activa o sintomática o enfermedad hepática crónica.
8. Antecedentes de disfunción adrenal.
9. Enfermedad cardiaca de relevancia clínica, tal y como refleja el infarto del miocardio, o eventos trombóticos arteriales en los últimos 6 meses, angina grave o inestable, o bien enfermedad cardiaca Clase II-IV según los criterios de la Asociación Cardiológica de Nueva York (New York Heart Association, NYHA) o fracción de eyección cardiaca <50% al inicio del estudio (Anexo 2).
10. Fibrilación auricular u otra arritmia cardíaca que requiera tratamiento farmacológico.
11. Otros tumores malignos (en un periodo de 5 años), a excepción del cáncer de piel no melanoma.
12. Administración de una terapia en investigación o procedimiento quirúrgico invasivo (sin incluir la castración quirúrgica) en los 30 días previos al ciclo 1, día 1, o bien si el paciente está participando en otro ensayo clínico.
13. Cualquier estado o situación que, según el criterio del investigador, pudiera poner al sujeto en riesgo, pueda confundir los resultados del estudio o interferir con la participación del sujeto en este estudio.

E.5 End points

E.5.1

Primary end point(s)

Overall survival

Superviviencia general

E.5.1.1

Timepoint(s) of evaluation of this end point

Randomization up to the time of death from any cause

Aleatorización hasta el momento de la muerte por cualquier causa.

E.5.2

Secondary end point(s)

1) Radiographic progression-free survival
2) Time to next subsequent therapy for prostate cancer
3) Time to initiation of chemotherapy
4) Time to prostate specific antigen progression
5) Time to next skeletal-related event

1) Supervivencia radiográfica libre de progresión
2) Tiempo hasta el siguiente tratamiento para el cáncer de próstata
3) Tiempo hasta el inicio de quimioterapia
4) Tiempo hasta la progresión del antigen específico
5) Tiempo hasta el siguiente evento óseo relacionado

E.5.2.1

Timepoint(s) of evaluation of this end point

1) From randomization, up to disease progression or death from any cause (up to Month 60)
2, 3 & 4) From randomization to time to the occurrence of each event
5) From randomization to time to the occurrence of one of the following: clinical fracture, spinal cord compression, palliative radiation to bone, surgery to bone

1) Desde la aleatorización hasta la progresión de la enfermedad o muerte por cualquier causa (hasta el mes 60)
2, 3 y 4) Desde la aleatorización hasta la aparición de cualquiera de los eventos
5) Desde la aleatorización hasta la aparición de uno de los siguientes eventos: fractura clínica, compresión de la médula espinal, radiación ósea paliativa, cirugía ósea.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers

Biomarcadores

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

Yes

E.8.2.3.1

Comparator description

Agonistas del LHRH u orquiectomía

LHRH agonists or orchiectomy

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

123

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

Belgium

Brazil

Bulgaria

Canada

Chile

China

Colombia

Czech Republic

Denmark

Finland

France

Germany

Hungary

Israel

Italy

Japan

Korea, Republic of

Malaysia

Mexico

Netherlands

New Zealand

Peru

Poland

Portugal

Romania

Russian Federation

Singapore

Slovakia

South Africa

Spain

Sweden

Turkey

Ukraine

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

Última visita del último paciente

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

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:

320

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

950

F.2 Gender

F.2.1

Female

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

F.3.3.1

Women of childbearing potential not using contraception

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

667

F.4.2.2

In the whole clinical trial

1270

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)

In the event of a positive study result at either of the interim analyses or at the final analysis, all subjects will have the opportunity to enroll in an open-label Extension Phase of this protocol. The Extension Phase will allow subjects to receive active drug (ZYTIGA plus prednisone) until ZYTIGA becomes commercially available in the subject?s country

En el caso de obtener resultados positivos en cualquiera de los análisis intermedios o en el análisis final, todos los sujetos tendrán la oportunidad de ser incluidos en una fase de extensión abierta de este protocolo. La fase de extensión permitirá a los sujetos recibir el fármaco activo (ZYTIGA más prednisona) hasta que ZYTIGA esté disponible comercialmente en el país del sujeto.

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

2013-01-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-18

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

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