Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson's Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa (NCT NCT03881371)

NCT ID: NCT03881371

Last Updated: 2024-03-20

Results Overview

The mean total daily "OFF" time was assessed by 24-hour patient diary cards, of safinamide 100 mg/day compared to placebo, given as add-on therapy in PD patients with motor fluctuations on stable doses of L-dopa. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period: * "OFF" (Stiffness, marked decrease in mobility, or immobility). * "ON" without dyskinesia (Good or practically normal mobility without dyskinesia). * "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort). * "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself). * Asleep (Time spent asleep).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 307 participants
• Primary outcome timeframe: At baseline and Week 16
• Results posted on: 2024-03-20

Participant Flow

A total of 307 patients were randomized at approximately 31 study centres in China between 01-Aug-2019 to 20-Aug-2021.

Patients who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. The study was composed of a screening period (up to 2 weeks prior to the start of treatment, with 1 screening visit) and a treatment period (16 weeks).

Participant milestones

Measure	Safinamide Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Overall Study STARTED	153	154
Overall Study Number Treated	151	154
Overall Study COMPLETED	137	130
Overall Study NOT COMPLETED	16	24

Reasons for withdrawal

Measure	Safinamide Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Overall Study Adverse Event	8	9
Overall Study Death	1	0
Overall Study Lost to Follow-up	1	0
Overall Study Non-Compliance with Study Drug	0	2
Overall Study Physician Decision	3	3
Overall Study Withdrawal by Subject	2	10
Overall Study Discontinuation from Study	1	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson's Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa

Baseline characteristics by cohort

Measure	Safinamide n=151 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=154 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Total n=305 Participants Total of all reporting groups
Age, Continuous	61.4 Years STANDARD_DEVIATION 9.29 • n=5 Participants	61.8 Years STANDARD_DEVIATION 9.28 • n=7 Participants	61.6 Years STANDARD_DEVIATION 9.27 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	69 Participants n=7 Participants	128 Participants n=5 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	85 Participants n=7 Participants	177 Participants n=5 Participants
Race/Ethnicity, Customized Chinese	151 Participants n=5 Participants	154 Participants n=7 Participants	305 Participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline and Week 16

Population: Full analysis set population (FAS) included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The mean total daily "OFF" time was assessed by 24-hour patient diary cards, of safinamide 100 mg/day compared to placebo, given as add-on therapy in PD patients with motor fluctuations on stable doses of L-dopa. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period:

• "OFF" (Stiffness, marked decrease in mobility, or immobility).
• "ON" without dyskinesia (Good or practically normal mobility without dyskinesia).
• "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort).
• "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself).
• Asleep (Time spent asleep).

Outcome measures

Measure	Safinamide n=151 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=154 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the Mean Total Daily "OFF" Time	-1.93 Hours Standard Deviation 2.556	-0.88 Hours Standard Deviation 2.543

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The pain severity, was assessed by an 11-point Numerical Rating Scale (NRS). The NRS is a segmented numeric version of the visual analogue scale (VAS) in which a patient selects a whole number that best reflects the intensity of his/her pain, ranging from '0' ("no pain") to '10' ("worst possible pain").

Outcome measures

Measure	Safinamide n=151 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=154 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in Pain Severity, as Assessed by an 11 Point Numerical Rating Scale (NRS)	-0.0 Score on a Scale Standard Deviation 1.89	-0.0 Score on a Scale Standard Deviation 2.14

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The mean total daily "ON" time, as assessed by 24-hour patient diary cards. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period:

• "OFF" (Stiffness, marked decrease in mobility, or immobility).
• "ON" without dyskinesia (Good or practically normal mobility without dyskinesia).
• "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort).
• "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself).
• Asleep (Time spent asleep).

Outcome measures

Measure	Safinamide n=137 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=130 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the Mean Total Daily "ON" Time	1.30 Hours Standard Deviation 2.693	0.51 Hours Standard Deviation 2.875

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The mean daily "ON" time with no/non troublesome dyskinesia, as assessed by 24-hour patient diary cards. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period:

• "OFF" (Stiffness, marked decrease in mobility, or immobility).
• "ON" without dyskinesia (Good or practically normal mobility without dyskinesia).
• "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort).
• "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself).
• Asleep (Time spent asleep).

Outcome measures

Measure	Safinamide n=137 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=130 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the Mean Daily "ON" Time With no/Non Troublesome Dyskinesia	1.30 Hours Standard Deviation 2.927	0.39 Hours Standard Deviation 3.212

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The UPDRS comprises 3 parts that evaluates any complication of treatment: Part I: Evaluation of mentation or cognition, behavior and mood. Part II: Evaluation of the activities of daily life. Part III: Evaluation of motor function. Part IV: Evaluation of complications of therapy. The UPDRS performed by the Investigator with points assigned to each item in the scale based on the patient's response as well as observation and physical examination. Together Parts I-III contain 44 items, with each item scored on a 5-point scale. Part IV contains 11 questions with a scale ranging from 0 to 23. Thus, the final total score may range from 0 (no disability) to 199 (total disability). The UPDRS is the most commonly used scale in clinical studies to follow the longitudinal course of PD. Part I Evaluation of mentation or cognition, behavior and mood contains 4 items with each item scored on a 5 point scale, the scale ranging from 0 to 16.

Outcome measures

Measure	Safinamide n=134 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=128 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score During the "ON" Phase	-12.3 Change in score Standard Deviation 13.59	-5.8 Change in score Standard Deviation 12.30

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The UPDRS= Unified Parkinson's Disease Rating Scale; is the most commonly used scale in clinical studies to follow the longitudinal course of PD.

It is divided in 4 sections, each of them with several items. The score of each item is 0-1 or 0-4 (the majority) where 0 is no symptom while the highest score means the most severe symptom.

UPDRS part I: 4 items, score 0-16 (total); UPDRS part II: 13 items, score 0-52 (total); UPDRS part III: 14 items, score 0-108 (total) UPDRS part IV: it is dived in 3 sections. Section A=dyskinesias, 4 items, score 0-13 (total); section B=clinical fluctuations, 4 items, score 0-7 (total); section C=other complications, 3 items, score 0-3 (total).

The total score of the UPDRS (meaning of all the 4 parts) is 0-199 where 0 means no symptoms, 199 the most severe symptoms.

Outcome measures

Measure	Safinamide n=134 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=128 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the UPDRS Part II Activities of Daily Living (ADL) Score During the "ON" Phase	-2.7 Change in score Standard Deviation 4.45	-1.2 Change in score Standard Deviation 4.32

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The UPDRS= Unified Parkinson's Disease Rating Scale; is the most commonly used scale in clinical studies to follow the longitudinal course of PD.

It is divided in 4 sections, each of them with several items. The score of each item is 0-1 or 0-4 (the majority) where 0 is no symptom while the highest score means the most severe symptom.

UPDRS part I: 4 items, score 0-16 (total); UPDRS part II: 13 items, score 0-52 (total); UPDRS part III: 14 items, score 0-108 (total) UPDRS part IV: it is dived in 3 sections. Section A=dyskinesias, 4 items, score 0-13 (total); section B=clinical fluctuations, 4 items, score 0-7 (total); section C=other complications, 3 items, score 0-3 (total).

The total score of the UPDRS (meaning of all the 4 parts) is 0-199 where 0 means no symptoms, 199 the most severe symptoms.

Outcome measures

Measure	Safinamide n=134 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=128 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the UPDRS Part III (Motor Function) Score During the "ON" Phase	-8.2 Change in score Standard Deviation 9.64	-3.7 Change in score Standard Deviation 8.71

SECONDARY outcome

Timeframe: At week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The CGI-S scale measures global severity of illness at a given point in time. It is rated on a 7-point Likert-type scale ranging from 1 (normal, not ill at all) to 7 (extremely severe). The CGI-S was assessed at all visits, starting at baseline.

Outcome measures

Measure	Safinamide n=134 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=128 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Clinical Global Impression of Severity (CGI-S) Score Assessed at Week 16	3.6 Point on scale Standard Deviation 0.80	3.8 Point on scale Standard Deviation 0.95

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The CGI-C scale measured the change in the patient's clinical status from baseline using a 7-point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change. The change from the patient's baseline condition is assessed by the Investigator at all post-baseline visits.

Outcome measures

Measure	Safinamide n=134 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=128 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Clinical Global Impression of Change (CGI-C) Assessed at Week 16	3.0 Point on scale Standard Deviation 1.12	3.4 Point on scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: At baseline and Week 16

Population: The FAS population included all patients who provided informed consent, were randomized and received at least 1 dose or partial dose of the study drug.

The PDQ-39 comprises 39 questions measuring eight dimensions of health: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication and bodily pain. Dimension scores are coded on a scale of 0 (perfect health as assessed by the measure) to 100 (worst health as assessed by the measure).

Outcome measures

Measure	Safinamide n=134 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=128 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Change From Baseline to Week 16 in the Parkinson's Disease Questionnaire-39 Items (PDQ-39) Score	-6.42 Change in score Standard Deviation 10.223	-2.67 Change in score Standard Deviation 10.901

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])

Population: Safety population were included all patients who provided informed consent and received at least 1 dose or partial dose of study drug.

Evaluation of the safety and tolerability of safinamide compared with placebo in Chinese PD patients with motor fluctuations.

Outcome measures

Measure	Safinamide n=151 Participants Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=154 Participants Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TESAE, Related to Study Drug	4 Participants	3 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE	105 Participants	88 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE Related to study drug	54 Participants	40 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any Severe TEAE	4 Participants	4 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any Severe TEAE, Related to study drug	3 Participants	1 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE with Outcome of Death	1 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE with Outcome of Death to study drug	1 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TESAE	8 Participants	5 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE Leading to Study Withdrawal	8 Participants	9 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE Leading to Discontinuation of Study Drug	7 Participants	10 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TESAE Leading to Study Withdrawal	3 Participants	1 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TESAE Leading to Discontinuation of Study Drug	3 Participants	1 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE) Any TEAE Leading to Dose Reduction of Study Drug	7 Participants	2 Participants

Adverse Events

Safinamide

Serious events: 8 serious events

Other events: 42 other events

Deaths: 1 deaths

Placebo

Serious events: 5 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Measure	Safinamide n=151 participants at risk Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=154 participants at risk Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Injury, poisoning and procedural complications Head injury	0.00% 0/151 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.65% 1/154 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/151 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.65% 1/154 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Vascular disorders Hypertension	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Psychiatric disorders Completed suicide	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Nervous system disorders Dizziness	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Nervous system disorders Vascular headache	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Nervous system disorders Parkinson's disease	0.00% 0/151 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.65% 1/154 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Cardiac disorders Ventricular extrasystoles	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.65% 1/154 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Cardiac disorders Angina unstable	0.00% 0/151 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.65% 1/154 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Gastrointestinal disorders Haemorrhoids	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
General disorders Chest discomfort	0.66% 1/151 • Number of events 1 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	0.00% 0/154 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])

Other adverse events

Measure	Safinamide n=151 participants at risk Patients received film-coated Safinamide tablets orally, once daily (od) with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.	Placebo n=154 participants at risk Patients received matching placebo orally, od with L-dopa and other (if any) anti-Parkinson drugs. After the Week 2 (ideally at Day 15), the dosage was adjusted from 50 mg to 100 mg and was maintained at 100 mg until the end of the study. Treatment continued daily for a total of 16 weeks.
Nervous system disorders Dyskinesia	11.9% 18/151 • Number of events 18 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	3.9% 6/154 • Number of events 6 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Nervous system disorders Dizziness	6.0% 9/151 • Number of events 15 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	6.5% 10/154 • Number of events 14 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Nervous system disorders Parkinson's disease	4.6% 7/151 • Number of events 7 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	9.1% 14/154 • Number of events 15 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Gastrointestinal disorders Constipation	4.0% 6/151 • Number of events 6 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	5.2% 8/154 • Number of events 8 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Musculoskeletal and connective tissue disorders Back pain	6.0% 9/151 • Number of events 9 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])	3.9% 6/154 • Number of events 6 • From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])

Additional Information

Valentina Zanin

Zambon S.p.A

Phone: +39 02 665241

Email: valentina.zanin@zambongroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER