Clinical trial NCT00605683: MOTION, Safinamide in Early IPD, as add-on to Dopamine Agonist
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Parkinson's Disease
Lead sponsor: Newron Pharmaceuticals SPA
Sponsor class: INDUSTRY
First posted: 2008-01-31
Enrollment: 679
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the changes from baseline to W24 in motor symptoms (UPDRS Section III).
timeFrame: 24 weeks
Secondary outcomes:
measure: 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
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Neurological Institute
state: Arizona
city: Oxnard
country: United States
facility: Pacific Neuroscience Medical Group
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Sunnyvale
country: United States
facility: Parkinson's Institute
state: California
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorder Center
state: Florida
city: Ft Lauderdale
country: United States
facility: Neurologic Consultants P.A.
state: Florida
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of SW Florida
state: Florida
city: Sunrise
country: United States
facility: Neurology Clinical Research Inc.
state: Florida
city: Tampa
country: United States
facility: University Of South Florida Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Columbus
country: United States
facility: Columbus Research Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University PD and Movement Disorders Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Albany
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Albany
state: New York
city: Manhasset
country: United States
facility: North Shore Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: Charlotte
country: United States
facility: The Neurological Institute
state: North Carolina
city: Druham
country: United States
facility: Duke University Health Systems
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dayton
country: United States
facility: Neurology Specialists
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Wynnewood
country: United States
facility: Lankenau Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital Español
city: Buenos Aires
country: Argentina
facility: Instituto de Neurociencias Buenos Aires S.A.
city: Capital Federal
country: Argentina
facility: Clinica IMECO
city: Capital Federal
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Capital Federal
country: Argentina
facility: Instituto de Investigaciones Neurológicas Raul Carrea FLENI
city: Capital Federal
country: Argentina
facility: Instituto Frenopatico S.A.
city: Ciudad Autonoma de Bs. As.
country: Argentina
facility: Instituto Medico Congreso
city: Ciudad Autonoma de
country: Argentina
facility: Instituto Argentino de Investigacion Neurologica SRL
city: Ciudad Autónoma de Bs. As.
country: Argentina
facility: Instituto INEBA
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Médico de Córdoba
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
city: Curitiba
country: Brazil
facility: Hospital das Clinicas da UFPR
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Salvador
country: Brazil
facility: Centro Pediatrico Professor Hosanna de Oliveira
city: Salvador
country: Brazil
facility: Hospital Universitario Professor Edgard Santos - UFBA
city: Sofia
country: Bulgaria
facility: CCB Medical Institute - Ministry of Interior
city: Sofia
country: Bulgaria
facility: First MHAT - Sofia AD
city: Sofia
country: Bulgaria
facility: MHAT Tokuda Hospital Sofia AD
city: Sofia
country: Bulgaria
facility: Shatcvd - Nch Ead
city: Sofia
country: Bulgaria
facility: SHATNP 'Sv. Naum' EAD
city: Sofia
country: Bulgaria
facility: UMHAT 'Tsaritsa Yoanna - ISUL' EAD
city: Pointe-Claire
country: Canada
facility: Dynamik Research Inc.
state: Quebec
city: Kingston
country: Canada
facility: Kingston General Hospital
city: Markham
country: Canada
facility: Centre For Movement Disorders
city: Ottawa
country: Canada
facility: Parkinson's and Neurodegenerative Disorders Clinic
city: Toronto
country: Canada
facility: Toronto Western Hospital - University Health Network
city: Santiago
country: Chile
facility: Hospital Barros Luco Trudeau
city: Valdivia
country: Chile
facility: Hospital Base Valdivia
city: Viña del Mar
country: Chile
facility: Clinica Ciudad del Mar
city: Bogota
country: Colombia
facility: Centro de Investigaciones del Sistema Nervioso Limitada
city: Bogotá
country: Colombia
facility: Fundación Clínica Abood Shaio
city: Bucaramanga
country: Colombia
facility: Instituto del Corazón
city: Osijek
country: Croatia
facility: Clinical Hospital Osijek
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Zagreb
country: Croatia
facility: Clinical Hospital "Sestre Milosrdnice"
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Brno
country: Czech Republic
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czech Republic
facility: Privatni neurologicka ambulance
city: Ostrava
country: Czech Republic
facility: Poliklinika Modry pavilon
city: Praha 10
country: Czech Republic
facility: Clintrials.r.o.
city: Praha 2
country: Czech Republic
facility: VFN Praha
city: Kuopio
country: Finland
facility: Itä-Suomen yliopisto Kuopion kampus
city: Lappeenranta
country: Finland
facility: Etelä-Karjalan keskussairaala
city: Oulu
country: Finland
facility: ODL Terveys Oy
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Charité Mitte
city: Berlin
country: Germany
facility: Ehret Reinhard
city: Berlin
country: Germany
facility: St. Josef-Hospital
city: Tuebingen
country: Germany
facility: Eberhard-Karls-Universitaet
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Hyderabad
country: India
facility: Krishna Institute of Medical Sciences
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences
city: Mangalore'
country: India
facility: Mallikatta Neuro and Research Centre
city: Mumbai
country: India
facility: T.N. Medical College & B.Y.L. Nair Hospital
city: Nagpur
country: India
facility: Brain & Mind Institute
city: New Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS)
city: Pune
country: India
facility: Poona Hospital & Research Center
city: Vishakapatnam
country: India
facility: Andhra Medical College
city: Catania
country: Italy
facility: AO Universitaria Policlinico di Catania
city: Chieti
country: Italy
facility: Fondazione Università Gabriele D'Annunzio
city: Lido di Camaiore
country: Italy
facility: Ospedale Versilia
city: Milano
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
city: Milano
country: Italy
facility: Istituti Clinici di Perfezionamento
city: Napoli
country: Italy
facility: Università degli Studi "Federico II"
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma
city: Roma
country: Italy
facility: IRCCS S. Raffaele Pisana
city: Roma
country: Italy
facility: Ospedale San Giovanni Battista Ordine di Malta
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Colonia La Fama
country: Mexico
facility: Instituto Nacional de Neurologia
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara "Fray Antonio Alcalde"
city: Mexico
country: Mexico
facility: Medical Sur
city: Monterrey
country: Mexico
facility: Instituto de Información de Investigación en Salud Mental
city: Callao
country: Peru
facility: Hospital Alberto Sabogal Sologuren
city: Lima
country: Peru
facility: Clinica Anglo Americana
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: Gdansk
country: Poland
facility: Pomorskie Centr.Traumatologii WSS im.M.Kopernika
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Banska Bystrica
country: Slovakia
facility: MU Dr. Beata Dupejova Neurologicka ambulancia s.r.o
city: Bratislava
country: Slovakia
facility: FNsP Bratislava pracovisko Kramare
city: Bratislava
country: Slovakia
facility: Poliklinika Tehelna
city: Levoca
country: Slovakia
facility: Vseobecna nemocnica s poliklinikou Levoca a.s.
city: Trnava
country: Slovakia
facility: Fakultna nemocnica Trnava
city: Zilina
country: Slovakia
facility: Nestatne zdravotnicke zariadenie
city: Johannesburg
country: South Africa
facility: Sandton Clinic
state: Gauteng
city: Durban
country: South Africa
facility: Dr CC Coetzee Inc
state: KZ-Natal
city: Cape Town
country: South Africa
facility: Constantiaberg Medi-Clinic
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Durban
country: South Africa
facility: St. Augustine's Medical Mews
city: Pretoria
country: South Africa
facility: Willows Medical Centre
city: Barcelona
country: Spain
facility: H Clinic i Provincial
city: Barcelona
country: Spain
facility: H de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: H Mutua de Terrassa
city: Madrid
country: Spain
facility: Fundacion H. Alcorcon
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: San Sebastian
country: Spain
facility: Policlinica Guipuzcoa
Study officials:
affiliation: Merck Serono S.A., Geneva
name: Jonathan Willmer, MD
role: STUDY_DIRECTOR
References: