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

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 or memantine within 4 weeks before start of the study
treatment or requiring these medications during the treatment period

- Depot neuroleptic during the study or within 1 injection cycle or oral neuroleptics
(stable dose of quetiapine less than 100 mg/day for 8 weeks prior to Visit 1 will be
allowed) within 4 weeks prior to Visit 1 (Screening)

- Drug that has hepatotoxic potential (e.g., tamoxifen) within 4 weeks prior to Visit 1
(Screening), or radiation therapy, or a drug with cytotoxic potential (e.g.,
chemotherapy) within 1 year prior to the Screening visit.

- Subjects who, in the judgment of the Investigator, is likely to be non-compliant or
uncooperative during the study

- Women who are pregnant, lactating, or who are attempting to conceive

- Women of childbearing potential not willing to use an adequate contraceptive method
(unless surgically sterilized) for 4 weeks prior to, during, and 4 weeks after the
last dose of trial medication

- Clinically significant ophthalmologic abnormality such as patients with albinism,
family history of hereditary retinal disease, progressive and/or severe diminution of
corrected visual acuity, retinitis pigmentosa, any active retinopathy or ocular
inflammation (uveitis), or progressive, severe diabetic retinopathy

- Known hypersensitivity to the trial treatment(s), including placebo or other
comparator drug(s)

- Legal incapacity or limited legal capacity