Safinamide in Idiopathic Parkinson's Disease (IPD) With Motor Fluctuations, as add-on to Levodopa

Idiopathic Parkinson's Disease Clinical Trial

— SETTLE  

Official title:

A Phase III, Double-blind, Placebo-controlled, Randomised Trial to Determine the Efficacy and Safety of a Dose Range of 50 to 100 mg/Day of Safinamide, as add-on Therapy, in Subjects With Idiopathic Parkinson's Disease With Motor Fluctuations, Treated With a Stable Dose of Levodopa and Who May be Receiving Concomitant Treatment With Stable Doses of a Dopamine Agonist, an Anticholinergic and/or Amantadine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00627640
• Other study ID #: 27919
• Secondary ID: IND: 63,901Eudra
• Status: Completed
• Phase: Phase 3
• First received: February 13, 2008
• Last updated: March 27, 2013
• Start date: February 2009
• Est. completion date: March 2012

Study information

• Verified date: June 2012
• 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 dopamine-containing 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.

Safinamide is an inhibitor of MAO-B. This is a phase III trial to evaluate the efficacy and safety of safinamide (50 and 100 mg p.o. q.a.m.) compared to placebo as add-on therapy to a stable dose to levodopa in subjects with advance idiopathic Parkinson's Disease.

The principal efficacy measure is the increase in mean daily "on" time during the 18-hr diary recording period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 549
• 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:

Male and female between the ages of 30 to 80 years with diagnosis of idiopathic Parkinson's Disease of more than 5 years duration, with a Hoehn and Yahr stage of I-IV during an "off" phase.

Be levodopa-responsive and have been receiving treatment with a stable dose of levodopa for at least 4 weeks.

Have motor fluctuations, with >1.5 hours "off" time during the day. Be able to maintain an accurate and complete diary (18-hour)

Exclusion Criteria:

Patients with medical conditions and/or taking concomitant medications that would have put them at risk, interfered with the study evaluations, or made them unable to complete the requirements of the study;.

Be in a late stage of Parkinson's Disease, and experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms.

Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.

Have received treatment with safinamide previously. History of, or current depression psychosis (e.g. schizophrenia or psychotic depression) Evidence of dementia or cognitive dysfunction. History of allergic response to anticonvulsants, levodopa, or other anti-Parkinsonian agents.

Hypersensitivity or contraindications to MAO-B inhibitors. 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.

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

Drug:
• Safinimide 50-100 mg/day
Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative
• Matching Placebo
Matching Placebo

Locations

Country	Name	City	State
Australia	Concord Repatriation General Hospital	Concord
Australia	Central Coast Neuroscience Research	East Gosford
Austria	Univ.Klinik Graz	Graz
Austria	Univ.Klinik Innsbruck	Innsbruck
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	U.Z Antwerpen	Edegem
Belgium	Jessa Ziekenhuis - Campus Virga Jesse	Hasselt
Belgium	ZNA Hoge Beuken	Hoboken
Belgium	Heilig Hart Roeselare - Campus westlaan	Roeselare
Belgium	AZ Sint-Augustinus	Wilrijk
Canada	King David	Halifax
Canada	Research Site	Halifax	Nova Scotia
Canada	Kingston General Hospital	Kingston
Canada	Parkinson's and Neurodegenerative Disorders Clinic	Ottawa	Ontario
Canada	Dynamic Clinical Research Group	Pointe Claire	Quebec
Canada	University Health Network -Toronto Western Hosp.	Toronto	Ontario
Estonia	Tartu University Hospital	Tartu
France	CHU Hopital Gabriel Montpied	Clermont Ferrand
France	CHU La Miletrie	Miletrie Poitiers
France	CHU Nantes Hôpital Laennec - CIC Neurologie	Nantes Cedex
France	CHU de Nimes, Hopital Caremeau	Nimes Cedex
France	CIC-Hospital Purpan	Pavillon Riser Toulouse
Germany	Kliniken Beelitz GmbH	Beelitz-Heilstaetten
Germany	Charité Campus Virchow Universitaetsmedizin Berlin	Berlin
Germany	Ehret Reinhard	Berlin
Germany	St. Joseph-Krankenhaus Berlin-Weißensee	Berlin
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Arzneimittelforschung Leipzig GmbH	Leipzig
Germany	Philipps-Universitaet Marburg	Marburg
Germany	Praxis Dipl med Bodenschatz	Mittweida
Germany	Neurologisches Krankenhaus Muenchen	Muenchen
Germany	Eberhard-Karls-Universität	Tubingen
Germany	Universitätsklinikum	Ulm
Germany	Deutsche Klinik fuer Diagnostik	Wiesbaden
Hungary	Clinexpert Kereskedelmi es Szolgaltato Kft.	Budapest
Hungary	Fov.Onk.Peterfy S.Utcai Korh.-Rend.Int es Baleseti Kozp.	Budapest
Hungary	Fovárosi Önkormányzat Nyíro Gyula Kórhaz Neurologiai Osztály	Budapest
Hungary	Nyiro Gyula Korhaz	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	SOTE Neurlogia	Budapest
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc
Hungary	DE OEC Neurologiai Klinika	Móricz
Hungary	Peterfy S. Utcai Korhaz	Peterfy Sandor
Hungary	Sopron Medical Egeszsegugyi Szolgaltato Kft.	Sopron
Hungary	BAZ Country Hospital and Outpatient Clinic Dept. of Neurology Toxicology and Stroke	Szentpetri
India	M. S. Ramaiah Medical College and Hospital	Bangalore	Karna
India	Nizam's Institute of Medical Sciences	Hyderabad	Andh Prad
India	Mallikatta Neuro and Research Centre	Mangalore
India	BYL Nair Hospital ¬ TN Medical College	Mumbai Mahara
India	Brain & Mind Institute	Nagpur
India	All India Institute of Medical Sciences (AIIMS)	New Delhi	Delhi
India	Christian Medical College Hospital	Vellore
India	King George Hospital	Visakhapatnam	Andh Prad
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam Health Care Campus	Haifa
Israel	Rabin Medical Center	Petach-Tikva
Israel	Sheba Medical Center	Ramat-Gan
Israel	Sourasky Medical Center	Tel Aviv
Israel	Sieff Government Hospital	Zefat
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University College of Medicine	Seoul
Malaysia	University of Malaya Medical Center	Kuala Lumpur
Malaysia	Hospital Pulau Pinang	Pinang
Netherlands	Jeroen Bosch Ziekenhuis	Hertogenbosch
New Zealand	Auckland City Hospital	Aucklan
New Zealand	Van der Veer Institute for Parkinson's & Brain Research	Christchurch
New Zealand	Waikato Hospital	Hamilton
Slovakia	MU Dr.Beata Dupejová neurologicka ambulancia s.r.o	Banska Bystrica
Slovakia	Poliklinika Tehelna	Bratislava
Slovakia	Vseobecna nemocnica s poliklinikou Levoca	Levoca
Slovakia	Fakultna nemocnica Trnava Interna klinika	Slovak Republic
Slovakia	Nestatne zdravotnicke zariadenie Neurologicka ambulancia	Slovak Republic
Spain	Fundacion Hospital de Alcorcon	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	HU Carlos Haya	Malaga
Spain	Policlinica Guipuzcoa	San Sebastian
Switzerland	Inselspital Bern	Bern
Switzerland	Hopitaux Universitaires de Geneve - Hug	Geneve
Taiwan	Chang-Hua Christian Hospital	Chang Hua
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	Shin Kong Wu Ho-Su Memorial Hospital	Taipei
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Phramongkutklao Hospital	Bangkok
Thailand	Rajavithi Hospital	Bangkok
Thailand	Lampang Hospital	Lampang
Thailand	Sappasithiprasong Hospital	Ubonratchathani
United Kingdom	Fylde Coast Hospital	Blackpool
United Kingdom	Addenbrookes NHS Trust	Cambridge
United Kingdom	Southern General Hospital	Glasgow
United Kingdom	Royal Free Hospital	London
United Kingdom	Clinical Ageing Research Unit	Newcastle Upon Tyne
United States	Parkinson's Disease and Movement Disorder Center	Albany	New York
United States	Wesley Woods Geriatric Center	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Quest Research Institute	Bingham Farms	Michigan
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	Rush University Medical Center	Chicago	Illinois
United States	Columbus Research Institute	Columbus	Georgia
United States	Duke Movement Disorders Clinic	Durham	North Carolina
United States	Neurologic Consultants P.A.	Fort 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	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Neurological Institute of New York	New York	New York
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Parkinson's Disease Treatment Center of SW Florida	Port Charlotte	Florida
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
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

Sponsors (1)

Lead Sponsor	Collaborator
Newron

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Estonia,  France,  Germany,  Hungary,  India,  Israel,  Korea, Republic of,  Malaysia,  Netherlands,  New Zealand,  Slovakia,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the change from baseline to W24 in daily "on" time ("on" time without dyskinesia plus "on" time with minor dyskinesia)		24 weeks
Secondary	Evaluate the changes from baseline to W24 in Activities of Daily Living, cognition, dyskinesias, change in global clinical status, motor symptoms, motor fluctuations, change in levopoda dose and Health Related Quality of life		24 weeks