MOTION, Safinamide in Early IPD, as add-on to Dopamine Agonist

NCT ID: NCT00605683

Last Updated: 2013-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

679 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-11-30

Study Completion Date

2012-03-31

Brief Summary

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Parkinson's disease is a major neurodegenerative disorder in which there is a progressive loss of nigrostriatal dopaminergic neurons. The understanding that PD is a syndrome of dopamine (DA) deficiency led to the introduction in the clinical practice of L-dopa, a precursor of DA that crosses the blood brain barrier, and also to the use of selective inhibitors of MAO B, the major DA metabolising enzyme in man.

This is a double-blind, placebo-controlled, parallel-group, randomised, multi-centre, multi national, Phase III trial, comparing two doses of safinamide (50 and 100 mg p.o. q.a.m.) versus placebo as add-on therapy to a stable dose of a single dopamine agonist in subjects with early idiopathic Parkinson's Disease.

The principal efficacy measure, i.e., change in mean value of UPDRS - Section III total score from baseline to endpoint, was chosen based on regulatory guidance and prior use in other trials in similar populations.

Detailed Description

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Conditions

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Idiopathic Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

50 mg/day Safinamide

Group Type ACTIVE_COMPARATOR

Safinamide (as add-on therapy)

Intervention Type DRUG

Safinamide, (S)-(+)-2-\[4-(3-fluorobenzyloxy) benzylamino\] propanamide methanesulfonate, is an a-aminoamide derivative

2

Safinamide 100mg/day

Group Type ACTIVE_COMPARATOR

Safinamide (as add-on therapy)

Intervention Type DRUG

Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

3

Placebo 0mg/Safinamide

Group Type PLACEBO_COMPARATOR

Safinamide (as add-on therapy)

Intervention Type DRUG

Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

Interventions

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Safinamide (as add-on therapy)

Safinamide, (S)-(+)-2-\[4-(3-fluorobenzyloxy) benzylamino\] propanamide methanesulfonate, is an a-aminoamide derivative

Intervention Type DRUG

Safinamide (as add-on therapy)

Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

Intervention Type DRUG

Safinamide (as add-on therapy)

Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

Intervention Type DRUG

Other Intervention Names

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Apokyn Parlodel Mirapex Requip Cabergoline (not approved in US) Lisuride (not approved in US) Pergolide (withdrawn from US Market March 2007) Apokyn Parlodel Mirapex Requip Cabergoline (not approved in US) Lisuride (not approved in US) Pergolide (withdrawn from US Market March 2007) Apokyn Parlodel Mirapex Requip Cabergoline (not approved in US) Lisuride (not approved in US) Pergolide (withdrawn from US Market March 2007)

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of idiopathic Parkinson's Disease of less than 5 years duration, with a Hoehn and Yahr stage of I-III. The diagnosis should be based on medical history and neurological examination.
2. 30 to 80 years, inclusive, at screening.
3. If female, be either post menopausal for at least 2 years, surgically sterilised or have undergone hysterectomy or, if of child bearing potential they must be willing to avoid pregnancy by using an adequate method of contraception for four weeks prior to, during and four weeks after the last dose of study medication. For the purposes of this study, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive.
4. Receiving treatment with a single dopamine agonist at a stable dose for at least 4 weeks prior to the screening visit.
5. Willing and able to participate in the study and have provided written, informed consent.

Exclusion Criteria

To be eligible for inclusion in this study the subjects must not meet any of the following criteria:

1. Any indication of forms of Parkinsonism, other than idiopathic Parkinson's Disease.
2. If female, be pregnant or lactating.
3. Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.
4. Currently experiencing end of dose wearing off or on-off phenomena, disabling peak dose or biphasic dyskinesias, or unpredictable or widely swinging fluctuations.
5. Current clinically significant gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease, including acute gastric ulcer, hypertension that is not well controlled, asthma, chronic obstructive pulmonary disease (COPD), and Type I diabetes. Subjects with a history of gastric ulcer who have not had a recent episode of acute gastritis and are not currently experiencing gastric pain will be eligible for inclusion.
6. Second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within 3 months of the screening visit, or significant ECG abnormality, including QTc ≥ 450 msec (males) or ≥ 470 msec (females), where QTc is based on Bazett's correction method.
7. Have received treatment with safinamide previously.
8. Concomitant disease likely to interfere with the study medication (e.g. capable of altering absorption, metabolism or elimination of the study drug).
9. History of, or current psychosis (e.g. schizophrenia or psychotic depression) or a score ≥ 3 on item 2 (thought disorder) or 3 (depression) of the UPDRS, Section I at screening.
10. Evidence of dementia or cognitive dysfunction, as indicated by a MMSE score \< 24 or a score ≥ 3 on item 1 (mentation) of the UPDRS, Section I at screening.
11. Depression, as indicated by a GRID-HAMD (17-item scale) score \> 17 at screening.
12. History of allergic response to anticonvulsants or anti-Parkinsonian agents.
13. Mental or physical condition (e.g., neurotic behaviour, crippling degenerative arthritis, or limb amputation), which would preclude performing efficacy or safety assessments.
14. Hypersensitivity or contraindications to MAO B inhibitors.
15. Current history of severe dizziness or fainting on standing, due to postural hypotension.
16. Neoplastic disorder, which is either currently active or has been in remission for less than one year.
17. Participation in a clinical trial within 30 days of entry into the trial (screening visit) or has received treatment with any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to screening.
18. Treatment of their Parkinsonian symptoms with a medication, other than a stable dose of a single dopamine agonist, during the 8 weeks preceding the screening visit.
19. Treatment with any agent known to significantly inhibit or induce drug-metabolising enzymes (e.g., barbiturates, phenothiazines, etc.) within 4 weeks preceding the screening visit.
20. Treatment with opioids (e.g., tramadol, meperidine derivatives), SNRIs (e.g., venlafaxine, duloxetine), tri- or tetra-cyclic antidepressants, MAO inhibitors (e.g. selegiline), in the 8 weeks prior to the screening visit. Dextromethorphan will be permitted if used for treating cough.
21. Treatment with a depot neuroleptic within one injection cycle, or oral neuroleptics within 4 weeks prior to the screening visit.
22. Treatment with a drug that has hepatotoxic potential, e.g., tamoxifen, within 4 weeks, or received radiation therapy or a drug with cytotoxic potential, e.g., chemotherapy, within one year prior to the screening visit.
23. Diagnosis of HIV, or tests positive for Hepatitis C antibodies, or Hepatitis B surface antigen.
24. Any abnormality that the investigator deems to be clinically relevant, either on medical history, physical examination, ECG or in a diagnostic laboratory test.
25. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy.
26. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
Minimum Eligible Age

30 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Newron Pharmaceuticals SPA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan Willmer, MD

Role: STUDY_DIRECTOR

Merck Serono S.A., Geneva

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Arizona Neurological Institute

Phoenix, Arizona, United States

Site Status

Pacific Neuroscience Medical Group

Oxnard, California, United States

Site Status

San Francisco Clinical Research Center

San Francisco, California, United States

Site Status

Parkinson's Institute

Sunnyvale, California, United States

Site Status

Institute for Neurodegenerative Disorders

New Haven, Connecticut, United States

Site Status

Parkinson's Disease and Movement Disorder Center

Boca Raton, Florida, United States

Site Status

Neurologic Consultants P.A.

Fort Lauderdale, Florida, United States

Site Status

University Of Florida

Gainesville, Florida, United States

Site Status

Parkinson's Disease Treatment Center of SW Florida

Port Charlotte, Florida, United States

Site Status

Neurology Clinical Research Inc.

Sunrise, Florida, United States

Site Status

University Of South Florida Medical Center

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Medical College of Georgia

Augusta, Georgia, United States

Site Status

Columbus Research Institute

Columbus, Georgia, United States

Site Status

Northwestern University PD and Movement Disorders Center

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status

Parkinson's Disease and Movement Disorders Center of Albany

Albany, New York, United States

Site Status

North Shore Medical Center

Manhasset, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

New York University

New York, New York, United States

Site Status

The Neurological Institute

Charlotte, North Carolina, United States

Site Status

Duke University Health Systems

Druham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Neurology Specialists

Dayton, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Lankenau Hospital

Wynnewood, Pennsylvania, United States

Site Status

Butler Hospital

Providence, Rhode Island, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Hospital Español

Buenos Aires, , Argentina

Site Status

Instituto de Neurociencias Buenos Aires S.A.

Buenos Aires, , Argentina

Site Status

Clinica IMECO

Capital Federal, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Capital Federal, , Argentina

Site Status

Instituto de Investigaciones Neurológicas Raul Carrea FLENI

Capital Federal, , Argentina

Site Status

Instituto Frenopatico S.A.

Capital Federal, , Argentina

Site Status

Instituto Medico Congreso

Ciudad Autonoma de Bs. As., , Argentina

Site Status

Instituto Argentino de Investigacion Neurologica SRL

Ciudad Autonoma de, , Argentina

Site Status

Instituto INEBA

Ciudad Autónoma de Bs. As., , Argentina

Site Status

Hospital Privado Centro Médico de Córdoba

Córdoba, , Argentina

Site Status

Hospital Universitario Austral

Pilar, , Argentina

Site Status

Hospital das Clinicas da UFPR

Curitiba, , Brazil

Site Status

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Site Status

Centro Pediatrico Professor Hosanna de Oliveira

Salvador, , Brazil

Site Status

Hospital Universitario Professor Edgard Santos - UFBA

Salvador, , Brazil

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CCB Medical Institute - Ministry of Interior

Sofia, , Bulgaria

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First MHAT - Sofia AD

Sofia, , Bulgaria

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MHAT Tokuda Hospital Sofia AD

Sofia, , Bulgaria

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Shatcvd - Nch Ead

Sofia, , Bulgaria

Site Status

SHATNP 'Sv. Naum' EAD

Sofia, , Bulgaria

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UMHAT 'Tsaritsa Yoanna - ISUL' EAD

Sofia, , Bulgaria

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Dynamik Research Inc.

Pointe-Claire, Quebec, Canada

Site Status

Kingston General Hospital

Kingston, , Canada

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Centre For Movement Disorders

Markham, , Canada

Site Status

Parkinson's and Neurodegenerative Disorders Clinic

Ottawa, , Canada

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Toronto Western Hospital - University Health Network

Toronto, , Canada

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Hospital Barros Luco Trudeau

Santiago, , Chile

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Hospital Base Valdivia

Valdivia, , Chile

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Clinica Ciudad del Mar

Viña del Mar, , Chile

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Centro de Investigaciones del Sistema Nervioso Limitada

Bogotá, , Colombia

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Fundación Clínica Abood Shaio

Bogotá, , Colombia

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Instituto del Corazón

Bucaramanga, , Colombia

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Clinical Hospital Osijek

Osijek, , Croatia

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Clinical Hospital Center Rijeka

Rijeka, , Croatia

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Clinical Hospital "Sestre Milosrdnice"

Zagreb, , Croatia

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Clinical Hospital Centre Zagreb

Zagreb, , Croatia

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Fakultni nemocnice Brno

Brno, , Czechia

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Privatni neurologicka ambulance

Hradec Králové, , Czechia

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Poliklinika Modry pavilon

Ostrava, , Czechia

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Clintrials.r.o.

Prague, , Czechia

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VFN Praha

Prague, , Czechia

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Itä-Suomen yliopisto Kuopion kampus

Kuopio, , Finland

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Etelä-Karjalan keskussairaala

Lappeenranta, , Finland

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ODL Terveys Oy

Oulu, , Finland

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Charité Universitaetsmedizin Berlin - Campus Charité Mitte

Berlin, , Germany

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Ehret Reinhard

Berlin, , Germany

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St. Josef-Hospital

Berlin, , Germany

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Eberhard-Karls-Universitaet

Tübingen, , Germany

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Universitaetsklinikum Ulm

Ulm, , Germany

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Krishna Institute of Medical Sciences

Hyderabad, , India

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Nizam's Institute of Medical Sciences

Hyderabad, , India

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Mallikatta Neuro and Research Centre

Mangalore, , India

Site Status

T.N. Medical College & B.Y.L. Nair Hospital

Mumbai, , India

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Brain & Mind Institute

Nagpur, , India

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All India Institute of Medical Sciences (AIIMS)

New Delhi, , India

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Poona Hospital & Research Center

Pune, , India

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Andhra Medical College

Visakhapatnam, , India

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AO Universitaria Policlinico di Catania

Catania, , Italy

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Fondazione Università Gabriele D'Annunzio

Chieti, , Italy

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Ospedale Versilia

Lido di Camaiore, , Italy

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Fondazione San Raffaele del Monte Tabor

Milan, , Italy

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Istituti Clinici di Perfezionamento

Milan, , Italy

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Università degli Studi "Federico II"

Napoli, , Italy

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Azienda Ospedaliera Universitaria di Parma

Parma, , Italy

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IRCCS S. Raffaele Pisana

Roma, , Italy

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Ospedale San Giovanni Battista Ordine di Malta

Roma, , Italy

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Policlinico Tor Vergata

Roma, , Italy

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Hospital Civil de Guadalajara "Fray Antonio Alcalde"

Guadalajara, , Mexico

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Instituto Nacional de Neurologia

La Fama, , Mexico

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Medical Sur

México, , Mexico

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Instituto de Información de Investigación en Salud Mental

Monterrey, , Mexico

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Hospital Alberto Sabogal Sologuren

Callao, , Peru

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Clinica Anglo Americana

Lima, , Peru

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Hospital Nacional Guillermo Almenara Irigoyen

Lima, , Peru

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Pomorskie Centr.Traumatologii WSS im.M.Kopernika

Gdansk, , Poland

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Hospital de Santa Maria

Lisbon, , Portugal

Site Status

MU Dr. Beata Dupejova Neurologicka ambulancia s.r.o

Banská Bystrica, , Slovakia

Site Status

FNsP Bratislava pracovisko Kramare

Bratislava, , Slovakia

Site Status

Poliklinika Tehelna

Bratislava, , Slovakia

Site Status

Vseobecna nemocnica s poliklinikou Levoca a.s.

Levoča, , Slovakia

Site Status

Fakultna nemocnica Trnava

Trnava, , Slovakia

Site Status

Nestatne zdravotnicke zariadenie

Žilina, , Slovakia

Site Status

Sandton Clinic

Johannesburg, Gauteng, South Africa

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Dr CC Coetzee Inc

Durban, KZ-Natal, South Africa

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Constantiaberg Medi-Clinic

Cape Town, , South Africa

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Groote Schuur Hospital

Cape Town, , South Africa

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St. Augustine's Medical Mews

Durban, , South Africa

Site Status

Willows Medical Centre

Pretoria, , South Africa

Site Status

H Clinic i Provincial

Barcelona, , Spain

Site Status

H de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

H Mutua de Terrassa

Barcelona, , Spain

Site Status

Policlinica Guipuzcoa

Donostia / San Sebastian, , Spain

Site Status

Fundacion H. Alcorcon

Madrid, , Spain

Site Status

Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Countries

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Israel United States Argentina Brazil Bulgaria Canada Chile Colombia Croatia Czechia Finland Germany India Italy Mexico Peru Poland Portugal Slovakia South Africa Spain

Other Identifiers

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63,901

Identifier Type: -

Identifier Source: secondary_id

EudraCT: 2007-002963-28

Identifier Type: -

Identifier Source: secondary_id

27918

Identifier Type: -

Identifier Source: org_study_id