Effect of Safinamide on Parkinson's Disease Related Chron... | NCT03841604

ID	Type	Description	Link
2017-002426-20	EudraCT Number

Label	Type	Description	Intervention Names
Experimental	Experimental	Safinamide methanesulfonate film coated tablets once daily, 50 mg and 100 mg. Safinamide methanesulfonate 50 mg and 100 mg tablets was administered orally, OD, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA. Subjects received study drug 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards). The dose of 100 mg/day (titrated from 50 mg/day after 1 week) was selected based on the results of previous studies in patients with PD and from the results of a post hoc analysis that investigated the effects of safinamide on pain.	Drug: Safinamide Methanesulfonate
Placebo	Placebo Comparator	Safinamide methanesulfonate matching placebo film coated tablets once daily. The matching placebo was administered orally, OD, in tablets, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA.	Other: Safinamide methanesulfonate matching placebo

Name	Type	Description	Arm Group Labels	Other Names
Safinamide Methanesulfonate	Drug	50 mg, 100 mg	Experimental	Xadago

Measure	Description	Time Frame
Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set	To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.	Baseline and Week 16
Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set	To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.	Baseline and Week 16

Measure	Description	Time Frame
Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline	Reduction in pain severity (based on the "average worst pain experienced in the last 7 days") of ≥ 2 points was assessed by an 11-point NRS (numerical rating scale), compared to baseline. Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant must be 30 years of age or older, at the time of signing the informed consent.
Diagnosed with IPD by using the United Kingdom Parkinson's Disease Society Brain Bank criteria for more than 5 years duration.
Receiving treatment with a stable dose of oral L-Dopa (including controlled release [CR], immediate release [IR] or a combination of CR/IR), with and without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine for at least 4 weeks prior to the randomisation (baseline visit).
Hoehn and Yahr stage between 2-3 (inclusive) during the "ON" phase at the screening visit.
Experiencing motor fluctuations following optimum titration of treatment medications and within the 4 weeks immediately prior to randomisation.
Experiencing chronic pain (i.e. ongoing for ≥3 months prior to screening visit); the Investigator must consider chronic pain directly related to PD and not explained by any other health problem (e.g. peripheral neuropathy, organ disease or arthritis pain) OR consider the intensity of chronic pain specifically aggravated by PD.
If taking regular analgesics, the treatment regimen should be stable in the 4 weeks prior to the randomisation visit.
Able to maintain an accurate and complete electronic diary with the help of a caregiver.
Male or female

•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i.Not a woman of childbearing potential (WOCBP) OR ii.A WOCBP who agrees to follow the contraceptive guidance
Capable of giving signed informed consent

Exclusion Criteria:

Any form of Parkinsonism other than IPD.
Diagnosis of chronic migraine (>15 days per month) or cancer pain.
History of bipolar disorder, depression, schizophrenia or other psychotic disorder requiring treatment with neuroleptics.
History of dementia or cognitive dysfunction.
Severe, peak dose or biphasic dyskinesia.
Unpredictable or widely swinging fluctuations.
Ophthalmologic history including any of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease.
Moderate or severe liver failure using the Child-Pugh classification score.
History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders.
Allergy/sensitivity, intolerance or contraindications to Safinamide.
Treatment with monoamine oxidase inhibitors (MAOIs), levodopa infusion, pethidine, fluoxetine, fluvoxamine less than 4 weeks prior to the randomisation visit
Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest
Previous treatment with Safinamide in the 9 months before the screening visit
Mini-Mental State Exam (MMSE) total score <24 at screening.
NRS score ≤ 4 points at randomization visit.
Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for participants while in the study

Name	Affiliation	Role
Charlotte Keywood, MD	Zambon SpA	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Medizinische Universitat Innsbruck		Innsbruck		6020	Austria
Institut für Neuroimmunologische und Neurodegenerative Erkrankungen

ID	Title	Description
FG000	Experimental	Safinamide methanesulfonate film coated tablets once daily, 50 mg and 100 mg. Safinamide methanesulfonate 50 mg and 100 mg tablets was administered orally, OD, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA. Subjects received study drug 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards). The dose of 100 mg/day (titrated from 50 mg/day after 1 week) was selected based on the results of previous studies in patients with PD and from the results of a post hoc analysis that investigated the effects of safinamide on pain

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 27, 2020	Nov 10, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set

To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.

Full Analysis Set:All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (39 and 20) above reported is the number of subjects with observed average worst pain score.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units	Counts
Participants	OG00039 OG00120

Title

Denominators

Categories

Title	Measurements
	OG000-1.6± 2.01 OG001-0.8± 1.29

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Model Repeated Measures		0.1695		Mean Difference (Net)	-0.7	Standard Error of the Mean	0.52	2-Sided	95	-1.75	0.32					Superiority

Primary

Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set

Per Protocol Set : The PP set was a subset of subjects in the FAS who completed the study and for whom no relevant protocol deviations were documented

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units	Counts
Participants

Secondary

Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline

Reduction in pain severity (based on the "average worst pain experienced in the last 7 days") of ≥ 2 points was assessed by an 11-point NRS (numerical rating scale), compared to baseline. Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.

Posted

Count of Participants

Participants

Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units	Counts
Participants

Secondary

The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain

CGI-C (Clinical Global Impression - Change) score for pain is a seven-point scale that indicates the patient's impression of change for relevant symptoms. It ranges from "substantial improvement" to "substantial worsening":

= substantial improvement;
= moderate improvement;
= minimum improvement;
= No change;
= Minimum worsening;
= moderate worsening;
= substantial worsening. of course the higher the score, the worse the outcome.

Full Analysis Set: Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n above reported (37 and 20) is the number of subjects with observed CGI-C score.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Secondary

The Global Impression of Severity (CGI-S) Score for Pain at Week 16

The CGI-S (Clinical Global Impression - Severity) score is a seven-point scale which asks the clinician one question: "considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated as follow:

= normal, not at all ill;
= borderline mentally ill;
= mildly ill;
= moderately ill;
= markedly ill;
= severely ill;
= among the most severely ill patients. of course the higher the score, the worse the outcome.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (44 and 22) here reported is the number of subjects with observed CGI-S score.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units

Secondary

The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain

The Patients' Global Impression of Change (PGI-C) scale is designed to capture the subject's perception of change in activity limitations, symptoms, emotions, an overall quality of life. These areas are captured using a 7- point scale, indicating:

= no change (or condition has got worse);
= almost the same, hardly any change at all;
= a little better, but not noticeable change;
= somewhat better, but the change has not made any real difference;
= moderately better, and a slight but noticeable change;
= better and a definite improvement that has made a real and worthwhile difference;
= a great deal better, and a considerable improvement that has made all the difference.

Of course, the higher the score, the better the outcome.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (33 and 20) here reported is the number of subjects with observed PGI-C score.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Secondary

Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints

This outcome describes the number of subjects which had concomitant assumption of pain drugs at different timepoints.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.

Posted

Number

participants

Baseline, weeks 4, 8 and 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units	Counts
Participants	OG000

Secondary

Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits

Total count of patients who used PRN (meaning "when necessary") Parkinson's Disease Pain Medications was expressed both in number and in percentage.

The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized:

as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints;
in the number of days on which PRN PD pain medication was taken at different timepoints.

Full Analysis Set:All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.

Posted

Count of Participants

Participants

at Baseline and weeks 4, 8 and 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units	Counts

Secondary

Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints

The analysis of amount of concomitant PRN PD pain medications as reported in the subject diary was summarized:

as the number of days on which PRN PD pain medication was taken at different timepoints.
as the number of subjects who were taking pain medication in the 7 days preceding visits at different timepoints.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug.

Posted

Mean

Standard Deviation

number of days

At Baseline and weeks 4, 8 and 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Units	Counts
Participants

Secondary

Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score

The Hospital Anxiety and Depression Scale (HADS) was devised to measure anxiety and depression in a general medical population of patients through a unique questionnaire which takes 2-5 min to be completed. The questionnaire consists of a total of 14 items: seven items for the anxiety subscale (HADS Anxiety) and seven items for the depression subscale (HADS Depression). HADS Anxiety focus mainly on symptoms of generalized anxiety disorder and HADS Depression is focused on anhedonia, the main symptom of depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for anxiety subscale and the same for depression subscale, where:

0-7 = Normal 8-10 = Borderline abnormal (borderline case). 11-21 = Abnormal (case) The two subscores are then summed up to obtain a total Hospital Anxiety and Depression Scale (HADS). The total scale range is 0-42. The higher the score, the worse the anxiety/depression status.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (33 and 20) is the number of subjects with observed HADS score.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo

Secondary

The Change From Baseline to Week 16 in MDS-UPDRS

Change in the MDS-UPDRS = Movement Disorder Society-Unified Parkinson's Disease Rating Scale The MDS-UPDRS is defined by 4 Parts, each composed by a different number of items. Each item is rated on a 5-point Likert-type scale (ranging from 0 to 4); Part I (non-motor experiences of daily living; 13 items) Part II (motor experiences of daily living;13 items) Part III (motor examination; 33 items) Part IV (motor complications; 6 items) The MDS-UPDRS has a minimum score of 0 and a maximum score of 260. The higher the score, the more severe the impairment.

Full Analysis Set: All randomized subjects in the study, with at least one measurement of the primary efficacy variable following at least one dose of study drug. Please note that n (31 and 19) is the number of subjects with observed MDS-UPDRS score

Posted

Mean

Standard Deviation

score on a scale

Baseline and Week 16

ID	Title	Description
OG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
OG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Pterygium	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Constipation	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected46 at risk EG0010 events0 affected25 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected46 at risk EG0010 events0 affected25 at risk
Nausea	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected46 at risk EG0010 events0 affected25 at risk
Dental caries	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Tongue ulceration	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Fatigue	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0012 events2 affected25 at risk
Pyrexia	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0012 events2 affected25 at risk
Oedema peripheral	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Pain	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Nasopharyngitis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0011 events1 affected25 at risk
Respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Blood pressure increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected46 at risk EG0010 events0 affected25 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Dizziness	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0011 events1 affected25 at risk
Dyskinesia	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected46 at risk EG0010 events0 affected25 at risk
Hyperkinesia	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected46 at risk EG0010 events0 affected25 at risk
Headache	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Lacunar infarction	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Motor dysfunction	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Paraesthesia	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Parkinson's disease	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Somnolence	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Syncope	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Hallucination	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0011 events1 affected25 at risk
Anxiety	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Depression	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Hallucination, visual	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected46 at risk EG0011 events1 affected25 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk
Hypertension	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected46 at risk EG0010 events0 affected25 at risk

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

ID	Title	Description
BG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg
BG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Experimental	Safinamide methanesulfonate film coated tablets once daily Safinamide Methanesulfonate: 50 mg, 100 mg	0	46	0	46	19	46
EG001	Placebo	Safinamide methanesulfonate matching placebo film coated tablets once daily Safinamide methanesulfonate matching placebo: 50 mg, 100 mg	0	25	2	25	12	25