A Trial to Explore the Potential Benefit of Safinamide on... | NCT01211587

Status Module

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
PD-CRS subscale scores	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.

Eligibility Module

Eligibility Criteria

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

Facility	Status	City	State	ZIP	Country	Contacts
The Parkinson's Institute		Sunnyvale	California		United States
Mayo Clinic Florida

Type	Date	Date Unknown
Release	Mar 21, 2017
Reset	May 1, 2017

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases