A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL-GROUP PHASE II STUDY TO EXPLORE THE POTENTIAL BENEFICIAL EFFECTS OF SAFINAMIDE ON COGNITION IN NON-DEMENTED PATIENTS WITH IDIOPATHIC PARKINSON´S DISEASE (PD) AND COGNITIVE IMPAIRMENT

Not Applicable

• Conditions: -G20 Parkinson´s disease; Parkinson´s disease; G20

• Registration Number: PER-094-10
• Lead Sponsor: EWRON PHARMACEUTICALS SpA.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-12-15
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: Not specified
• Target Recruitment: 9

Inclusion Criteria

• 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)

Exclusion Criteria

• 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
• Currently participating to another clinical trial or who participated in a previous clinical trial within 30 days prior to Visit 1 (Screening) or who received any investigational product within 30 days or five half-lives, whichever was longer, prior to Visit 1 (Screening)
• Previously treated with safinamide
• Clinically significant hypertension or contraindications or hypersensitivity to monoamine oxidase-Type B (MAO-B) inhibitors
• Anticholinergic medication and/or amantadine within 4 weeks prior to the Screening visit
• Opioids (e.g., tramadol and meperidine derivatives) or MAO inhibitors (e.g., selegiline) within 8 weeks prior to Visit 1 (Screening) Dextromethorphan will be allowed to treat cough. One tricyclic- or tetracyclic antidepressant or trazodone will be permitted if taken at bedtime at a low dose as a sleeping aid
• Acetylcholinesterase inhibitors o

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:Total score reduction in the PD-CRS at 12 weeks compared to the Baseline. The PD-CRS detects early cognitive impairment in Parkinsons 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.<br>Measure:Parkinsons Disease Cognitive Rating Scale (PD-CRS)<br>Timepoints:12 weeks<br>