Safinamide in Idiopathic Parkinson's Disease (IPD) With Motor Fluctuations, as add-on to Levodopa
SETTLE
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
3 other identifiers
interventional
549
19 countries
115
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2009
Typical duration for phase_3
115 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 13, 2008
CompletedFirst Posted
Study publicly available on registry
March 3, 2008
CompletedStudy Start
First participant enrolled
February 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2012
CompletedMarch 29, 2013
June 1, 2012
2.9 years
February 13, 2008
March 27, 2013
Conditions
Outcome Measures
Primary Outcomes (1)
Evaluate the change from baseline to W24 in daily "on" time ("on" time without dyskinesia plus "on" time with minor dyskinesia)
24 weeks
Secondary Outcomes (1)
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
Study Arms (2)
1
EXPERIMENTAL1 active (50 - 100 mg/day)
2
PLACEBO COMPARATORInterventions
Safinamide, (S)-(+)-2-\[4-(3-fluorobenzyloxy) benzylamino\] propanamide methanesulfonate, is an a-aminoamide derivative
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (121)
University of Alabama at Birmingham
Birmingham, Alabama, United States
Barrow Neurological Institute
Phoenix, Arizona, United States
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
San Francisco Clinical Research Center
San Francisco, California, United States
Parkinson's Institute
Sunnyvale, California, United States
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States
Parkinson's Disease and Movement Disorder Center
Boca Raton, Florida, United States
Neurologic Consultants P.A.
Fort Lauderdale, Florida, United States
University of Florida
Gainesville, Florida, United States
Parkinson's Disease Treatment Center of SW Florida
Port Charlotte, Florida, United States
Neurology Clinical Research Inc.
Sunrise, Florida, United States
University Of South Florida Medical Center
Tampa, Florida, United States
Wesley Woods Geriatric Center
Atlanta, Georgia, United States
Columbus Research Institute
Columbus, Georgia, United States
Northwestern University PD and Movement Disorders Center
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
University of Maryland Medical Center
Baltimore, Maryland, United States
Boston University School of Medicine
Boston, Massachusetts, United States
Quest Research Institute
Bingham Farms, Michigan, United States
Parkinson's Disease and Movement Disorder Center
Albany, New York, United States
North Shore Medical Center
Manhasset, New York, United States
Neurological Institute of New York
New York, New York, United States
The Neurological Institute
Charlotte, North Carolina, United States
Duke Movement Disorders Clinic
Durham, North Carolina, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
Concord Repatriation General Hospital
Concord, Australia
Central Coast Neuroscience Research
East Gosford, Australia
Univ.Klinik Graz
Graz, Austria
Univ.Klinik Innsbruck
Innsbruck, Austria
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, Belgium
Research Site
Halifax, Nova Scotia, Canada
Parkinson's and Neurodegenerative Disorders Clinic
Ottawa, Ontario, Canada
University Health Network -Toronto Western Hosp.
Toronto, Ontario, Canada
Dynamic Clinical Research Group
Pointe-Claire, Quebec, Canada
King David
Halifax, Canada
Kingston General Hospital
Kingston, Canada
Tartu University Hospital
Tartu, Estonia
CHU Hopital Gabriel Montpied
Clermont-Ferrand, France
CHU La Miletrie
Miletrie Poitiers, France
CHU Nantes Hôpital Laennec - CIC Neurologie
Nantes, France
CHU de Nimes, Hopital Caremeau
Nîmes, France
CIC-Hospital Purpan
Pavillon Riser Toulouse, France
Kliniken Beelitz GmbH
Beelitz-Heilstätten, Germany
Charité Campus Virchow Universitaetsmedizin Berlin
Berlin, Germany
Ehret Reinhard
Berlin, Germany
St. Joseph-Krankenhaus Berlin-Weißensee
Berlin, Germany
Universitaetsklinikum Goettingen
Göttingen, Germany
Arzneimittelforschung Leipzig GmbH
Leipzig, Germany
Philipps-Universitaet Marburg
Marburg, Germany
Praxis Dipl med Bodenschatz
Mittweida, Germany
Neurologisches Krankenhaus Muenchen
München, Germany
Eberhard-Karls-Universität
Tübingen, Germany
Universitätsklinikum
Ulm, Germany
Deutsche Klinik fuer Diagnostik
Wiesbaden, Germany
Clinexpert Kereskedelmi es Szolgaltato Kft.
Budapest, Hungary
Fov.Onk.Peterfy S.Utcai Korh.-Rend.Int es Baleseti Kozp.
Budapest, Hungary
Fővárosi Önkormányzat Nyírő 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, Hungary
Nizam's Institute of Medical Sciences
Hyderabad, Andh Prad, India
King George Hospital
Visakhapatnam, Andh Prad, India
M. S. Ramaiah Medical College and Hospital
Bangalore, Karna, India
All India Institute of Medical Sciences (AIIMS)
New Delhi, National Capital Territory of Delhi, India
Mallikatta Neuro and Research Centre
Mangalore, India
BYL Nair Hospital ¬ TN Medical College
Mumbai Mahara, India
Brain & Mind Institute
Nagpur, India
Christian Medical College Hospital
Vellore, India
Barzilai Medical Center
Ashkelon, Israel
Rambam Health Care Campus
Haifa, Israel
Rabin Medical Center
Petah Tikva, Israel
Sheba Medical Center
Ramat Gan, Israel
Sieff Government Hospital
Safed, Israel
Sourasky Medical Center
Tel Aviv, Israel
Hospital Pulau Pinang
George Town, Malaysia
University of Malaya Medical Center
Kuala Lumpur, Malaysia
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
Auckland City Hospital
Aucklan, New Zealand
Van der Veer Institute for Parkinson's & Brain Research
Christchurch, New Zealand
Waikato Hospital
Hamilton, New Zealand
MU Dr.Beata Dupejová neurologicka ambulancia s.r.o
Banská Bystrica, Slovakia
Poliklinika Tehelna
Bratislava, Slovakia
Vseobecna nemocnica s poliklinikou Levoca
Levoča, Slovakia
Fakultna nemocnica Trnava Interna klinika
Slovak Republic, Slovakia
Nestatne zdravotnicke zariadenie Neurologicka ambulancia
Slovak Republic, Slovakia
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Severance Hospital, Yonsei University College of Medicine
Seoul, South Korea
Policlinica Guipuzcoa
Donostia / San Sebastian, Spain
Fundacion Hospital de Alcorcon
Madrid, Spain
Fundacion Jimenez Diaz
Madrid, Spain
HU Carlos Haya
Málaga, Spain
Inselspital Bern
Bern, Switzerland
Hopitaux Universitaires de Geneve - Hug
Geneva, Switzerland
Chang-Hua Christian Hospital
Chang-hua, Taiwan
Kaohsiung Veterans General Hospital
Kaohsiung City, Taiwan
Shin Kong Wu Ho-Su Memorial Hospital
Taipei, Taiwan
King Chulalongkorn Memorial Hospital
Bangkok, Thailand
Phramongkutklao Hospital
Bangkok, Thailand
Rajavithi Hospital
Bangkok, Thailand
Lampang Hospital
Lampang, Thailand
Sappasithiprasong Hospital
Ubonratchathani, Thailand
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 Kingdom
Related Publications (2)
Cattaneo C, Kulisevsky J. The Effects of Safinamide in Chinese and Non-Chinese Patients with Parkinson's Disease. Adv Ther. 2024 Feb;41(2):638-648. doi: 10.1007/s12325-023-02736-2. Epub 2023 Dec 9.
PMID: 38070039DERIVEDSchapira AH, Fox SH, Hauser RA, Jankovic J, Jost WH, Kenney C, Kulisevsky J, Pahwa R, Poewe W, Anand R. Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol. 2017 Feb 1;74(2):216-224. doi: 10.1001/jamaneurol.2016.4467.
PMID: 27942720DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Algirdas Kakarieka, MD
Merck Serono S.A., Geneva
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 13, 2008
First Posted
March 3, 2008
Study Start
February 1, 2009
Primary Completion
January 1, 2012
Study Completion
March 1, 2012
Last Updated
March 29, 2013
Record last verified: 2012-06