A Study to Evaluate the Efficacy and Safety of Safinamide Mesilate as Add-on Therapy to Levodopa in Parkinson's Disease Participants With Motor Fluctuation in South Korea

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the change at the 18th week from baseline in daily off time measured by participant diary and Parkinson's Disease Questionnaire-39 (PDQ-39) in participants with Parkinson's Disease who are receiving levodopa.

Official Title
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A Multi-center, Open-label Phase 4 Study Evaluating the Efficacy and Safety of Safinamide Mesilate as Add-on Therapy to Levodopa in Parkinson's Disease Patients With Motor Fluctuation in South Korea

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Safinamide Mesilate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age greater than or equal to (>=) 19 years at the time of informed consent Participants who meet the clinical diagnostic criteria of Movement Disorder Society (MDS) diagnostic criteria 2015 for Parkinson's disease, have motor fluctuations with >=1.5 hours of off time throughout the day which is confirmed at the time of Screening, and take levodopa 3 or more times a day Parkinson's Disease participants who are receiving levodopa without Catechol O-methyltransferase (COMT) inhibitor and/or Monoamine oxidase-B (MAO-B) inhibitor Be levodopa-responsive and have been receiving treatment with levodopa (including controlled-release [CR], immediate-release [IR], or a combination of CR and IR), and/or benserazide/carbidopa at a stable dose at least 4 weeks prior to the screening visit Dose of levodopa at the screening visit can be maintained without escalation during the 18-week treatment period Participants taking dopamine agonists are being treated at a stable dose for at least 4 weeks prior to the screening visit and can be maintained without dose adjustment during the 18-week treatment period Be able to maintain an accurate and complete diary with the help of a caregiver as needed, recording on time, on time with dyskinesia, off time, and time asleep Be able to provide written informed consent Participants whose cognitive function, at the discretion of an investigator, is at a level appropriate to participate in the clinical trial (that is., with a Global Deterioration Scale [GDS] score of 3 or less or a Clinical Dementia Rating [CDR] of 0.5 or less within 3 months prior to screening) Exclusion Criteria: Females who are planning for pregnancy, pregnant or breastfeeding Prior use of safinamide If participants have previously taken medication such as COMT inhibitor and/or MAO-B inhibitor, they have to take appropriate wash-out period for each medication (3 days for COMT inhibitor; 14 days for MAO-B inhibitor) Use of medications for depression or psychosis within 5 weeks prior to screening History of allergic response to levodopa, or other anti-Parkinsonian agents Hypersensitivity or contraindications to MAO-B inhibitors Confirmed ophthalmologic history including any of the following conditions: albino participants, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (that is, 20/70 on Snellen Chart), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy Participants who did not consent to having at least 7 days of washout period prior to visit 2, if known to take narcotic analgesics 7 days prior to screening visit (example, pethidine hydrochloride-containing products, tramadol hydrochloride, or tapentadol hydrochloride) History of serotonergic medications administration (example, tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors, selective noradrenaline reuptake inhibitor, or noradrenergic and serotonergic antidepressant) within 5 weeks prior to screening visit Administering central nervous system stimulants (example, methylphenidate hydrochloride, lisdexamfetamine mesilate) Administering dextromethorphan Participants with clinically significant liver function abnormalities defined as greater than (>) 1.5 times of the upper limit of the normal range of total bilirubin or >3 times of the upper limit of the normal range of Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST); re-examination and re-screening are allowed once within the screening period Have a history of hypersensitivity to any of the ingredients of the product Currently enrolled in another clinical trial or used any investigational drug/biologics or device within 30 days or 5*the half-life, whichever is longer, preceding informed consent

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safinamide Mesilate<br>Participants with parkinson's disease will be administered Safinamide Mesilate 50 milligram (mg) tablet, orally, once daily as add-on therapy to levodopa for up to 2 weeks. After 2 weeks, at the discretion of an investigator, dose of Safinamide Mesilate will be increased to 100 mg tablets (two tablets of 50 mg each), orally, once daily for up to 18 weeks. | Drug: Safinamide Mesilate<br>* Safinamide Mesilate oral tablets.<br>* Other names: ME2125;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Daily OFF Time | Information on daily off time and on time will be collected by participant diary card. Participants will receive participant diary card and will be trained on how to use it. At 30-minute intervals throughout the period, the participant/caregiver will record whether the participant is currently 1. in an on phase, 2. in an on phase with dyskinesia, 3. in an off phase, or 4. asleep. An off phase will be defined as lack of mobility, bradykinesia, or akinesia whereas in an on phase, the participant will be functioning as well as can be expected for that participant, irrespective of whether or not he or she is having dyskinesia. The daily off time is defined as the mean of the total daily off time during the last two 24-hour diary recording periods. Here, change from baseline in daily OFF time will be assessed. | Baseline, Week 18 | 
| Change From Baseline in PDQ-39 Score | PDQ-39 comprises of 39 questions measuring eight dimensions of health: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication and bodily pain. Each dimension total score ranges from 0 (perfect health as assessed by the measure) to 100 (worst health as assessed by the measure). | Baseline, Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating (MDS-UPDRS) Part 3 | The MDS-UPDRS is rating tool used to follow longitudinal course of Parkinson's Disease. It is made up of 4 parts that assess: Part 1: Non-motor Aspects of Experiences of Daily Living; Part 2: Motor Aspects of Experiences of Daily Living; Part 3: Motor Examination; Part 4: Motor Complications. Part 3 evaluates the motor function. The scale consists of 18 items, with 33 separate ratings being performed on scale from 0 (normal) to 4 (severe). The total score ranges of MDS-UPDRS Part 3 from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The participant's speech, facial expressions, ability to arise from a chair, posture, gait, postural stability (retropulsion test), and body bradykinesia will be assessed. In addition, tremor at rest, action or postural tremor of hands, rigidity, toe/finger taps, hand movements (open/close), rapid alternating movements of hands (pronation/supination), and leg agility will be assessed. | Baseline, Week 18 | 
| Change From Baseline in MDS-UPDRS Part 4 | The MDS-UPDRS is rating tool used to follow longitudinal course of Parkinson's Disease. It is made up of 4 parts that assess: Part 1: Non-motor Aspects of Experiences of Daily Living; Part 2: Motor Aspects of Experiences of Daily Living; Part 3: Motor Examination; Part 4: Motor Complications. Part 4 raters use historical/objective information to assess 2 motor complications, dyskinesias and motor fluctuations including OFF-state dystonia. Raters use information from participant, caregiver, and the examination to answer 6 questions. The duration of disability caused and functional impact of any dyskinesias experienced by the participant are rated on a scale of 0 to 4. Scale consists of 6 items being performed on scale from 0 (normal) to 4 (severe). The total score ranges from 0 to 24, lower score indicating better motor function and higher score indicating more severe motor symptoms. | Baseline, Week 18 | 
| Change From Baseline in King's Parkinson's Disease Pain Scale (KPPS) | KPPS is a Parkinson's Disease-specific pain scale that evaluates the localization, frequency, and intensity of pain. It has 14 items in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0 [none] to 3 [very severe]) multiplied by frequency (0 [never] to 4 [all the time]), resulting in a subscore of 0 to 12, the sum of which gives the total score range from 0 to 168. Higher scores are indicative of more severity and frequency of pain. | Baseline, Week 18 | 
| Change From Baseline in Mini-Mental State Examination (MMSE) | The MMSE is a brief practical screening test for cognitive dysfunction. The test consists of 5 sections (orientation, registration, attention and calculation, recall, and language) and has a total possible score of 30. Scores ranges from 0 (most impaired) to 30 (no impairment). It is useful as a quick method to assess the severity of cognitive dysfunction. | Baseline, Week 18 | 
| Number of Participants With Treatment-emergent Adverse events (TEAEs) and Serious Adverse Events (SAEs) | Safety assessments will consist of monitoring and recording all adverse events (AEs); regular monitoring of clinical laboratory parameters; vital signs and 12-lead electrocardiogram (ECG), body weight, urine pregnancy test and physical examinations. A TEAE is defined as an AE that emerges during treatment, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE is continuous. SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, inpatient hospitalization, requires prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), is a medically significant event. | Up to Week 19 | 
| Change From Baseline in Daily ON Time Without Dyskinesia | Information on daily off time and on time will be collected by participant diary card. Participants will receive participant diary card and will be trained on how to use it. At 30-minute intervals throughout the period, the participant/caregiver will record whether the participant is currently 1. in an on phase, 2. in an off phase, or 3. asleep. Here, change from baseline in daily ON time without dyskinesia will be assessed. An off phase will be defined as lack of mobility, bradykinesia, or akinesia whereas in an on phase, the participant will be functioning as well as can be expected for that participant, irrespective of whether or not he or she is having dyskinesia. The daily on time is defined as the mean of the total daily on time during the last two 24-hour diary recording periods. | Baseline, Week 18 |