MedPath

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

Phase 3
Completed
Conditions
Idiopathic Parkinson's Disease
Interventions
Registration Number
NCT00605683
Lead Sponsor
Newron Pharmaceuticals SPA
Brief Summary

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

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
679
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1Safinamide (as add-on therapy)50 mg/day Safinamide
2Safinamide (as add-on therapy)Safinamide 100mg/day
3Safinamide (as add-on therapy)Placebo 0mg/Safinamide
Primary Outcome Measures
NameTimeMethod
Evaluate the changes from baseline to W24 in motor symptoms (UPDRS Section III).24 weeks
Secondary Outcome Measures
NameTimeMethod
Evaluate the changes from baseline to W24 in activities of daily living, cognition, change in global clinical status, responder rates with regard to motor symptoms and health related quality of life24 weeks

Trial Locations

Locations (125)

Parkinson's Disease and Movement Disorder Center

🇺🇸

Boca Raton, Florida, United States

Medical College of Georgia

🇺🇸

Augusta, Georgia, United States

Parkinson's Disease and Movement Disorders Center of Albany

🇺🇸

Albany, New York, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Pacific Neuroscience Medical Group

🇺🇸

Oxnard, California, United States

Columbus Research Institute

🇺🇸

Columbus, Georgia, United States

Neurologic Consultants P.A.

🇺🇸

Ft Lauderdale, Florida, United States

Parkinson's Disease Treatment Center of SW Florida

🇺🇸

Port Charlotte, Florida, United States

Arizona Neurological Institute

🇺🇸

Phoenix, Arizona, United States

University Of Florida

🇺🇸

Gainesville, Florida, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Parkinson's Institute

🇺🇸

Sunnyvale, California, United States

Neurology Clinical Research Inc.

🇺🇸

Sunrise, Florida, United States

University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Hospital das Clinicas da UFPR

🇧🇷

Curitiba, Brazil

Northwestern University PD and Movement Disorders Center

🇺🇸

Chicago, Illinois, United States

Instituto de Neurociencias Buenos Aires S.A.

🇦🇷

Buenos Aires, Argentina

Centre For Movement Disorders

🇨🇦

Markham, Canada

Parkinson's and Neurodegenerative Disorders Clinic

🇨🇦

Ottawa, Canada

University Of South Florida Medical Center

🇺🇸

Tampa, Florida, United States

Boston University School of Medicine

🇺🇸

Boston, Massachusetts, United States

North Shore Medical Center

🇺🇸

Manhasset, New York, United States

New York University

🇺🇸

New York, New York, United States

Duke University Health Systems

🇺🇸

Druham, North Carolina, United States

Lankenau Hospital

🇺🇸

Wynnewood, Pennsylvania, United States

Butler Hospital

🇺🇸

Providence, Rhode Island, United States

Hospital Español

🇦🇷

Buenos Aires, Argentina

Hospital Italiano de Buenos Aires

🇦🇷

Capital Federal, Argentina

Clinica IMECO

🇦🇷

Capital Federal, Argentina

Instituto de Investigaciones Neurológicas Raul Carrea FLENI

🇦🇷

Capital Federal, Argentina

Instituto Frenopatico S.A.

🇦🇷

Capital Federal, Argentina

Instituto Medico Congreso

🇦🇷

Ciudad Autonoma de Bs. As., Argentina

Hospital Privado Centro Médico de Córdoba

🇦🇷

Cordoba, Argentina

Instituto Argentino de Investigacion Neurologica SRL

🇦🇷

Ciudad Autonoma de, Argentina

Instituto INEBA

🇦🇷

Ciudad Autónoma de Bs. As., Argentina

Hospital Universitario Austral

🇦🇷

Pilar, Argentina

Hospital de Clinicas de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Centro Pediatrico Professor Hosanna de Oliveira

🇧🇷

Salvador, Brazil

Hospital Universitario Professor Edgard Santos - UFBA

🇧🇷

Salvador, Brazil

CCB Medical Institute - Ministry of Interior

🇧🇬

Sofia, Bulgaria

First MHAT - Sofia AD

🇧🇬

Sofia, Bulgaria

MHAT Tokuda Hospital Sofia AD

🇧🇬

Sofia, Bulgaria

UMHAT 'Tsaritsa Yoanna - ISUL' EAD

🇧🇬

Sofia, Bulgaria

Dynamik Research Inc.

🇨🇦

Pointe-Claire, Quebec, Canada

SHATNP 'Sv. Naum' EAD

🇧🇬

Sofia, Bulgaria

Kingston General Hospital

🇨🇦

Kingston, Canada

Toronto Western Hospital - University Health Network

🇨🇦

Toronto, Canada

Hospital Barros Luco Trudeau

🇨🇱

Santiago, Chile

Clinica Ciudad del Mar

🇨🇱

Viña del Mar, Chile

Fundación Clínica Abood Shaio

🇨🇴

Bogotá, Colombia

Centro de Investigaciones del Sistema Nervioso Limitada

🇨🇴

Bogota, Colombia

Hospital Base Valdivia

🇨🇱

Valdivia, Chile

Clinical Hospital Center Rijeka

🇭🇷

Rijeka, Croatia

Instituto del Corazón

🇨🇴

Bucaramanga, Colombia

Clinical Hospital "Sestre Milosrdnice"

🇭🇷

Zagreb, Croatia

Clinical Hospital Osijek

🇭🇷

Osijek, Croatia

Clinical Hospital Centre Zagreb

🇭🇷

Zagreb, Croatia

Privatni neurologicka ambulance

🇨🇿

Hradec Kralove, Czech Republic

Poliklinika Modry pavilon

🇨🇿

Ostrava, Czech Republic

VFN Praha

🇨🇿

Praha 2, Czech Republic

Clintrials.r.o.

🇨🇿

Praha 10, Czech Republic

Etelä-Karjalan keskussairaala

🇫🇮

Lappeenranta, Finland

ODL Terveys Oy

🇫🇮

Oulu, Finland

Krishna Institute of Medical Sciences

🇮🇳

Hyderabad, India

Nizam's Institute of Medical Sciences

🇮🇳

Hyderabad, India

Eberhard-Karls-Universitaet

🇩🇪

Tuebingen, Germany

Poona Hospital & Research Center

🇮🇳

Pune, India

Mallikatta Neuro and Research Centre

🇮🇳

Mangalore', India

All India Institute of Medical Sciences (AIIMS)

🇮🇳

New Delhi, India

AO Universitaria Policlinico di Catania

🇮🇹

Catania, Italy

Andhra Medical College

🇮🇳

Vishakapatnam, India

Fondazione Università Gabriele D'Annunzio

🇮🇹

Chieti, Italy

Ospedale Versilia

🇮🇹

Lido di Camaiore, Italy

Istituti Clinici di Perfezionamento

🇮🇹

Milano, Italy

Fondazione San Raffaele del Monte Tabor

🇮🇹

Milano, Italy

IRCCS S. Raffaele Pisana

🇮🇹

Roma, Italy

Università degli Studi "Federico II"

🇮🇹

Napoli, Italy

Policlinico Tor Vergata

🇮🇹

Roma, Italy

Ospedale San Giovanni Battista Ordine di Malta

🇮🇹

Roma, Italy

Azienda Ospedaliera Universitaria di Parma

🇮🇹

Parma, Italy

Hospital Civil de Guadalajara "Fray Antonio Alcalde"

🇲🇽

Guadalajara, Mexico

Medical Sur

🇲🇽

Mexico, Mexico

Hospital Alberto Sabogal Sologuren

🇵🇪

Callao, Peru

Hospital de Santa Maria

🇵🇹

Lisboa, Portugal

Pomorskie Centr.Traumatologii WSS im.M.Kopernika

🇵🇱

Gdansk, Poland

Poliklinika Tehelna

🇸🇰

Bratislava, Slovakia

Fakultna nemocnica Trnava

🇸🇰

Trnava, Slovakia

Vseobecna nemocnica s poliklinikou Levoca a.s.

🇸🇰

Levoca, Slovakia

Nestatne zdravotnicke zariadenie

🇸🇰

Zilina, Slovakia

Sandton Clinic

🇿🇦

Johannesburg, Gauteng, South Africa

Constantiaberg Medi-Clinic

🇿🇦

Cape Town, South Africa

Dr CC Coetzee Inc

🇿🇦

Durban, KZ-Natal, South Africa

Willows Medical Centre

🇿🇦

Pretoria, South Africa

H Clinic i Provincial

🇪🇸

Barcelona, Spain

Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

Fundacion H. Alcorcon

🇪🇸

Madrid, Spain

H Mutua de Terrassa

🇪🇸

Barcelona, Spain

Policlinica Guipuzcoa

🇪🇸

San Sebastian, Spain

Neurology Specialists

🇺🇸

Dayton, Ohio, United States

Shatcvd - Nch Ead

🇧🇬

Sofia, Bulgaria

H de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Groote Schuur Hospital

🇿🇦

Cape Town, South Africa

San Francisco Clinical Research Center

🇺🇸

San Francisco, California, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Ehret Reinhard

🇩🇪

Berlin, Germany

Charité Universitaetsmedizin Berlin - Campus Charité Mitte

🇩🇪

Berlin, Germany

St. Josef-Hospital

🇩🇪

Berlin, Germany

St. Augustine's Medical Mews

🇿🇦

Durban, South Africa

Universitaetsklinikum Ulm

🇩🇪

Ulm, Germany

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

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

🇸🇰

Banska Bystrica, Slovakia

Itä-Suomen yliopisto Kuopion kampus

🇫🇮

Kuopio, Finland

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

🇮🇳

Mumbai, India

Instituto Nacional de Neurologia

🇲🇽

Colonia La Fama, Mexico

Instituto de Información de Investigación en Salud Mental

🇲🇽

Monterrey, Mexico

Clinica Anglo Americana

🇵🇪

Lima, Peru

Hospital Nacional Guillermo Almenara Irigoyen

🇵🇪

Lima, Peru

Fakultni nemocnice Brno

🇨🇿

Brno, Czech Republic

Brain & Mind Institute

🇮🇳

Nagpur, India

FNsP Bratislava pracovisko Kramare

🇸🇰

Bratislava, Slovakia

Institute for Neurodegenerative Disorders

🇺🇸

New Haven, Connecticut, United States

The Neurological Institute

🇺🇸

Charlotte, North Carolina, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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