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

A Phase III, Double-blind, Placebo-controlled Randomised Trial to Determine the Efficacy and Safety of a Low (50 mg/Day) and High (100 mg/Day) Dose of Safinamide, as add-on Therapy, in Subjects With Early Idiopathic Parkinson's Disease Treated With a Stable Dose of a Single Dopamine Agonist

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Parkinson's Disease
• Intervention / Treatment: Drug: Safinamide (as add-on therapy); Drug: Safinamide (as add-on therapy)

• Study Type: Interventional
• Enrollment (Actual): 679
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Español
  • Buenos Aires, Argentina
    • Instituto de Neurociencias Buenos Aires S.A.
  • Capital Federal, Argentina
    • Clinica IMECO
  • Capital Federal, Argentina
    • Hospital Italiano de Buenos Aires
  • Capital Federal, Argentina
    • Instituto de Investigaciones Neurologicas Raul Carrea FLENI
  • Capital Federal, Argentina
    • Instituto Frenopatico S.A.
  • Ciudad Autonoma de, Argentina
    • Instituto Argentino de Investigacion Neurologica SRL
  • Ciudad Autonoma de Bs. As., Argentina
    • Instituto Medico Congreso
  • Ciudad Autónoma de Bs. As., Argentina
    • Instituto INEBA
  • Cordoba, Argentina
    • Hospital Privado Centro Medico de Cordoba
  • Pilar, Argentina
    • Hospital Universitario Austral
• Brazil
  • Curitiba, Brazil
    • Hospital das Clínicas da UFPR
  • Porto Alegre, Brazil
    • Hospital de Clinicas de Porto Alegre
  • Salvador, Brazil
    • Centro Pediatrico Professor Hosanna de Oliveira
  • Salvador, Brazil
    • Hospital Universitario Professor Edgard Santos - UFBA
• Bulgaria
  • Sofia, Bulgaria
    • CCB Medical Institute - Ministry of Interior
  • Sofia, Bulgaria
    • First MHAT - Sofia AD
  • Sofia, Bulgaria
    • MHAT Tokuda Hospital Sofia AD
  • Sofia, Bulgaria
    • Shatcvd - Nch Ead
  • Sofia, Bulgaria
    • SHATNP 'Sv. Naum' EAD
  • Sofia, Bulgaria
    • UMHAT 'Tsaritsa Yoanna - ISUL' EAD
• Canada
  • Kingston, Canada
    • Kingston General Hospital
  • Markham, Canada
    • Centre for Movement Disorders
  • Ottawa, Canada
    • Parkinson's and Neurodegenerative Disorders Clinic
  • Toronto, Canada
    • Toronto Western Hospital - University Health Network
  • Quebec
    • Pointe-Claire, Quebec, Canada, H9R 3J1
      • Dynamik Research Inc.
• Chile
  • Santiago, Chile
    • Hospital Barros Luco Trudeau
  • Valdivia, Chile
    • Hospital Base Valdivia
  • Viña del Mar, Chile
    • Clínica Ciudad del Mar
• Colombia
  • Bogota, Colombia
    • Centro de Investigaciones del Sistema Nervioso Limitada
  • Bogotá, Colombia
    • Fundación Clinica Abood Shaio
  • Bucaramanga, Colombia
    • Instituto del Corazon
• Croatia
  • Osijek, Croatia
    • Clinical Hospital Osijek
  • Rijeka, Croatia
    • Clinical Hospital Center Rijeka
  • Zagreb, Croatia
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia
    • Clinical Hospital "Sestre milosrdnice"
• Czech Republic
  • Brno, Czech Republic
    • Fakultni nemocnice Brno
  • Hradec Kralove, Czech Republic
    • Privatni neurologicka ambulance
  • Ostrava, Czech Republic
    • Poliklinika Modry pavilon
  • Praha 10, Czech Republic
    • Clintrials.r.o.
  • Praha 2, Czech Republic
    • VFN Praha
• Finland
  • Kuopio, Finland
    • Itä-Suomen yliopisto Kuopion kampus
  • Lappeenranta, Finland
    • Etela-Karjalan Keskussairaala
  • Oulu, Finland
    • ODL Terveys Oy
• Germany
  • Berlin, Germany
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Berlin, Germany
    • Ehret Reinhard
  • Berlin, Germany
    • St. Josef-Hospital
  • Tuebingen, Germany
    • Eberhard-Karls-Universitaet
  • Ulm, Germany
    • Universitaetsklinikum Ulm
• India
  • Hyderabad, India
    • Nizam's Institute of Medical Sciences
  • Hyderabad, India
    • Krishna Institute of Medical Sciences
  • Mangalore', India
    • Mallikatta Neuro and Research Centre
  • Mumbai, India
    • T.N. Medical College & B.Y.L. Nair Hospital
  • Nagpur, India
    • Brain & Mind Institute
  • New Delhi, India
    • All India Institute Of Medical Sciences (AIIMS)
  • Pune, India
    • Poona Hospital & Research Center
  • Vishakapatnam, India
    • Andhra Medical College
• Italy
  • Catania, Italy
    • AO Universitaria Policlinico di Catania
  • Chieti, Italy
    • Fondazione Università Gabriele D'Annunzio
  • Lido di Camaiore, Italy
    • Ospedale Versilia
  • Milano, Italy
    • Fondazione San Raffaele del Monte Tabor
  • Milano, Italy
    • Istituti Clinici di Perfezionamento
  • Napoli, Italy
    • Universita degli Studi "Federico II"
  • Parma, Italy
    • Azienda Ospedaliera Universitaria di Parma
  • Roma, Italy
    • Policlinico Tor Vergata
  • Roma, Italy
    • IRCCS S. Raffaele Pisana
  • Roma, Italy
    • Ospedale San Giovanni Battista Ordine di Malta
• Mexico
  • Colonia La Fama, Mexico
    • Instituto Nacional de Neurologia
  • Guadalajara, Mexico
    • Hospital Civil de Guadalajara "Fray Antonio Alcalde"
  • Mexico, Mexico
    • Medical Sur
  • Monterrey, Mexico
    • Instituto de Informacion de Investigacion en Salud Mental
• Peru
  • Callao, Peru
    • Hospital Alberto Sabogal Sologuren
  • Lima, Peru
    • Hospital Nacional Guillermo Almenara Irigoyen
  • Lima, Peru
    • Clinica Anglo Americana
• Poland
  • Gdansk, Poland
    • Pomorskie Centr.Traumatologii WSS im.M.Kopernika
• Portugal
  • Lisboa, Portugal
    • Hospital de Santa Maria
• Slovakia
  • Banska Bystrica, Slovakia
    • MU Dr. Beata Dupejova Neurologicka ambulancia s.r.o
  • Bratislava, Slovakia
    • Poliklinika Tehelna
  • Bratislava, Slovakia
    • FNsP Bratislava pracovisko Kramare
  • Levoca, Slovakia
    • Vseobecna nemocnica s poliklinikou Levoca a.s.
  • Trnava, Slovakia
    • Fakultna nemocnica Trnava
  • Zilina, Slovakia
    • Nestatne zdravotnicke zariadenie
• South Africa
  • Cape Town, South Africa
    • Constantiaberg Medi-clinic
  • Cape Town, South Africa
    • Groote Schuur Hospital
  • Durban, South Africa
    • St. Augustine's Medical Mews
  • Pretoria, South Africa
    • Willows Medical Centre
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • Sandton Clinic
  • KZ-Natal
    • Durban, KZ-Natal, South Africa
      • Dr CC Coetzee Inc
• Spain
  • Barcelona, Spain
    • H Clinic i Provincial
  • Barcelona, Spain
    • H de la Santa Creu i Sant Pau
  • Barcelona, Spain
    • H Mutua de Terrassa
  • Madrid, Spain
    • Fundación Jiménez Díaz
  • Madrid, Spain
    • Fundacion H. Alcorcon
  • San Sebastian, Spain
    • Policlinica Guipuzcoa
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States
      • Arizona Neurological Institute
  • California
    • Oxnard, California, United States
      • Pacific Neuroscience Medical Group
    • San Francisco, California, United States
      • San Francisco Clinical Research Center
    • Sunnyvale, California, United States
      • Parkinson's Institute
  • Connecticut
    • New Haven, Connecticut, United States
      • Institute for Neurodegenerative Disorders
  • Florida
    • Boca Raton, Florida, United States
      • Parkinson's Disease and Movement Disorder Center
    • Ft Lauderdale, Florida, United States
      • Neurologic Consultants P.A.
    • Gainesville, Florida, United States
      • University of Florida
    • Port Charlotte, Florida, United States
      • Parkinson's Disease Treatment Center of SW Florida
    • Sunrise, Florida, United States
      • Neurology Clinical Research Inc.
    • Tampa, Florida, United States
      • University of South Florida Medical Center
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University
    • Augusta, Georgia, United States
      • Medical College of Georgia
    • Columbus, Georgia, United States
      • Columbus Research Institute
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern University PD and Movement Disorders Center
  • Kansas
    • Kansas City, Kansas, United States
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Boston University School of Medicine
  • New York
    • Albany, New York, United States
      • Parkinson's Disease and Movement Disorders Center of Albany
    • Manhasset, New York, United States
      • North Shore Medical Center
    • New York, New York, United States
      • Columbia University Medical Center
    • New York, New York, United States
      • New York University
  • North Carolina
    • Charlotte, North Carolina, United States
      • The Neurological Institute
    • Druham, North Carolina, United States
      • Duke University Health Systems
  • Ohio
    • Cleveland, Ohio, United States
      • Cleveland Clinic
    • Dayton, Ohio, United States
      • Neurology Specialists
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health & Science University
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States
      • Lankenau Hospital
  • Rhode Island
    • Providence, Rhode Island, United States
      • Butler Hospital
  • Texas
    • Houston, Texas, United States
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 50 mg/day Safinamide	Drug: Safinamide (as add-on therapy); Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative; Other Names: Requip; Mirapex; Parlodel; Apokyn; Cabergoline (not approved in US); Lisuride (not approved in US); Pergolide (withdrawn from US Market March 2007); Drug: Safinamide (as add-on therapy); Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist; Other Names: Requip; Mirapex; Parlodel; Apokyn; Cabergoline (not approved in US); Lisuride (not approved in US); Pergolide (withdrawn from US Market March 2007)
Active Comparator: 2; Safinamide 100mg/day	Drug: Safinamide (as add-on therapy); Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative; Other Names: Requip; Mirapex; Parlodel; Apokyn; Cabergoline (not approved in US); Lisuride (not approved in US); Pergolide (withdrawn from US Market March 2007); Drug: Safinamide (as add-on therapy); Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist; Other Names: Requip; Mirapex; Parlodel; Apokyn; Cabergoline (not approved in US); Lisuride (not approved in US); Pergolide (withdrawn from US Market March 2007)
Placebo Comparator: 3; Placebo 0mg/Safinamide	Drug: Safinamide (as add-on therapy); Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative; Other Names: Requip; Mirapex; Parlodel; Apokyn; Cabergoline (not approved in US); Lisuride (not approved in US); Pergolide (withdrawn from US Market March 2007); Drug: Safinamide (as add-on therapy); Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist; Other Names: Requip; Mirapex; Parlodel; Apokyn; Cabergoline (not approved in US); Lisuride (not approved in US); Pergolide (withdrawn from US Market March 2007)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the changes from baseline to W24 in motor symptoms (UPDRS Section III).	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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 life	24 weeks

Collaborators and Investigators

• Sponsor: Newron Pharmaceuticals SPA
• Investigators: Study Director: Jonathan Willmer, MD, Merck Serono S.A., Geneva

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: January 18, 2008
• First Posted (Estimate): January 31, 2008

Study Record Updates

• Last Update Posted (Estimate): October 29, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Serotonin Receptor Agonists; Hormone Antagonists; Antioxidants; Emetics; Antiparkinson Agents; Anti-Dyskinesia Agents; Apomorphine; Ropinirole; Pramipexole; Cabergoline; Bromocriptine; Lisuride; Pergolide
• Other Study ID Numbers: 27918; 63,901; EudraCT: 2007-002963-28