A Trial to Explore the Potential Benefit of Safinamide on Cognitive Impairment Associated With Parkinson's Disease

NCT01211587 | Completed Phase 2 DMC

• 1 other identifier: EMR701165-024
• Study Type: interventional
• Target: 103
• Locations: 2 countries
• Sites: 15

Brief Summary

The purpose of this research trial is to determine if safinamide (experimental drug) can improve cognition in cognitively impaired but non-demented Parkinson's disease patients. The word "experimental" means the trial drug is not approved by Health Authorities (government authorities) and is still being tested for safety and effectiveness. Approximately one hundred (100) patients will participate in this research trial. The research trial will be conducted in approximately thirty (30) medical centers in the following countries: Argentina, Canada, Italy, Peru, South Africa, Spain and USA. The research trial will last until June 2012.

Conditions

Parkinson's Disease With Cognitive Impairments

Keywords

Parkinson's Disease; Cognition; Safinamide; Phase 2; Non-demented patients; Levodopa; Dopamine agonist

Outcome Measures

Primary Outcomes (1)

• Parkinson's Disease Cognitive Rating Scale (PD-CRS)

  Total score reduction in the PD-CRS at 12 weeks compared to the Baseline. The PD-CRS detects early cognitive impairment in Parkinson's disease. It is composed of 2 scales, the subcortical scale (items 1, 3, 4, 5, 7, 8, 9) and the cortical scale (items 2, 6). The total score of the subcortical scale is from 0 to 114. The total score of the cortical scale is from 0 to 20. The PD-CRS Total score represents the sum of scores on the cortical and subcortical scales. It ranges from 0 to 134. The more points, the less the impairment.

  12 weeks

Secondary Outcomes (25)

• PD-CRS subscale scores

  6 weeks

• PD-CRS subscale scores

  24 weeks

• PD-CRS total score

  24 weeks

• Dementia Rating Scale - 2 (DRS-2) total score

  12 weeks

• DRS-2 total score

  24 weeks

Study Arms (2)

100mg safinamide

EXPERIMENTAL

Two 50mg tablets of safinamide once per day for 12 weeks (weeks 1-12) Open Label part: Two 50mg tablets of safinamide once per day for 12 weeks (week 13-24)

Drug: safinamide

Placebo

PLACEBO COMPARATOR

Two 50mg tablets of placebo once per day for 12 weeks (weeks 1-12) Open Label part: Two 50mg tablets of safinamide once per day for 12 weeks (week 13-24)

Drug: placebo

Interventions

safinamide DRUG

Safinamide will be provided in tablets equivalent to 50 mg in blisters. After randomization, patients receiving safinamide will take two 50 mg tablets once per day for 12 weeks (weeks 1-12). During the open label phase, patients will receive 100mg of safinamide once per day (two 50 mg tablets) for 12 weeks (weeks 13-24).

100mg safinamide

placebo DRUG

Identical placebo tablets will be provided in blisters. After randomization, patients receiving placebo will take two tablets once per day for 12 weeks (weeks 1-12). During the open label phase, patients will receive 100mg of safinamide once per day (two 50 mg tablets) for 12 weeks (weeks 13-24).

Placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female outpatients (aged 45 to 80 years inclusive)
• Diagnosis of idiopathic Parkinson's Disease (PD) according to the UK PDS Brain Bank Criteria and a Hoehn and Yahr Stage of I to III (mild to moderate motor severity) at Screening. The diagnosis will be based on medical history and neurological examination
• Subjects and informants must report cognitive impairment in at least one cognitive domain on the PD Cognitive Questionnaire (PD-CQ).
• Cognitive impairment confirmed by a total score equal to- or below 26 on the Montreal Cognitive Assessment (MoCA)
• Be able to speak, read, and write in the language in which the tests are written and must be able to perform all the assessments in this language
• Receiving treatment with dopaminergic therapy (dopamine agonist and/or levodopa at a stable dose for at least four weeks prior to Screening and for the duration of the study)
• Understand and sign the appropriate approved Informed Consent Form(s), one for the study (mandatory) and one for the pharmacogenetic evaluation (optional)

You may not qualify if:

• Any indication of forms of Parkinsonism other than idiopathic PD
• Diagnosis of PD Dementia (probable, possible) according to the Clinical Diagnostic Criteria for Dementia Associated with PD
• Diagnosis of Dementia with Lewy Bodies according to the McKeith criteria.
• Subjects with any clinically significant DSM-IV-TR Axis I Disorders including major depression and severe anxiety; current diagnosis of substance abuse or history of alcohol or drug abuse for 3 months prior to Visit 1 (Screening)
• Mental/physical/social condition which could preclude performing efficacy or safety assessments
• Severe white matter disease, multiple lacunar infarcts, or signs of significant vascular changes on Magnetic Resonance Imaging (MRI)
• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
• Current history of severe dizziness or fainting on standing, due to postural hypotension
• Second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction in the three months prior to Visit 1 (Screening), or significant electrocardiogram (ECG) abnormality, including heart-rate corrected interval QT (QTC) \> 450 milliseconds (males) or \> 470 milliseconds (females), with QTC based on the Bazett's correction method
• Known diagnosis of human immunodeficiency virus (HIV) infection, positive results on tests for hepatitis B or C antibodies, or on tests for hepatitis B surface antigen (unless vaccinated)
• Neoplastic disease, either currently active or in remission for less than 1 year
• Clinically significant or unstable gastrointestinal, renal, hepatic, endocrine, pulmonary, or cardiovascular disease, including not well controlled hypertension, asthma, chronic obstructive pulmonary disease, and Type 1 diabetes that would, in the opinion of the Investigator, preclude participation to the study
• Any clinically relevant abnormality, either on medical history, physical and neurological examination, ECG, or by diagnostic laboratory tests that, in the opinion of the Investigator, could hinder participation to the study
• Currently experiencing end-of-dose wearing-off or on-off phenomena, disabling peak dose- or biphasic dyskinesia, or unpredictable or widely swinging fluctuations
• Any medical conditions and/or taking concomitant medications that could put them at risk, interfere with study evaluations, or prevent meeting the requirements of the study

Sponsors & Collaborators

• Newron Pharmaceuticals SPA: lead

Study Sites (15)

The Parkinson's Institute

Sunnyvale, California, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, United States

Location

Emory University

Atlanta, Georgia, United States

Location

Northwestern University

Chicago, Illinois, United States

Location

Rush University Medical Center

Chicago, Illinois, United States

Location

Johns Hopkins University

Baltimore, Maryland, United States

Location

US Medical Information Located in

Rockland, Massachusetts, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

Baylor College of Medicine Parkinson's Disease Center and Movement Disorders Clinic

Houston, Texas, United States

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital De La Santa Creui Sant Pau

Barcelona, Spain

Location

Hospital General de Catalunya

Barcelona, Spain

Location

USP Institut Universitari Dexeus

Barcelona, Spain

Location

Hosptial General Univ Gregorio Maranon

Madrid, Spain

Location

Hospital Mutual de Terrassa

Terrassa - Barcelona, Spain

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

safinamide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Jonathan Willmer, MD, FRCPC

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: September 29, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2012
• Last Updated: March 29, 2013

Record last verified: 2012-06

Locations

US (9); ES (6)