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

Idiopathic Parkinson's Disease Clinical Trial

— MOTION  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00605683
• Other study ID #: 27918
• Secondary ID: 63,901EudraCT: 2
• Status: Completed
• Phase: Phase 3
• First received: December 19, 2007
• Last updated: October 28, 2013
• Start date: November 2007
• Est. completion date: March 2012

Study information

• Verified date: March 2013
• Source: Newron
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 679
• Est. completion date: March 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

Drug:
• Safinamide (as add-on therapy)
Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative
• Safinamide (as add-on therapy)
Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist
• Safinamide (as add-on therapy)
Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Newron

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the changes from baseline to W24 in motor symptoms (UPDRS Section III).		24 weeks
Secondary	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