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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05312632
• Other study ID #: ME2125-M082-401
• Status: Completed
• Phase: Phase 4
• Start date: April 5, 2022
• Est. completion date: May 26, 2023

Study information

• Verified date: October 2023
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: May 26, 2023
• Est. primary completion date: May 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Male or female, age greater than or equal to (>=) 19 years at the time of informed consent

2. 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

3. 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

4. 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

5. Be able to provide written informed consent

6. 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:

1. Females who are planning for pregnancy, pregnant or breastfeeding

2. Prior use of safinamide

3. 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)

4. Use of medications for depression or psychosis within 5 weeks prior to screening

5. History of allergic response to levodopa, or other anti-Parkinsonian agents

6. Hypersensitivity or contraindications to MAO-B inhibitors

7. 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

8. 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)

9. 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

10. Administering central nervous system stimulants (example, methylphenidate hydrochloride, lisdexamfetamine mesilate)

11. Administering dextromethorphan

12. 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

13. Have a history of hypersensitivity to any of the ingredients of the product

14. 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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Safinamide Mesilate
Safinamide Mesilate oral tablets.

Locations

Country	Name	City	State
Korea, Republic of	Eisai Site #11	Busan
Korea, Republic of	Eisai Site #20	Busan
Korea, Republic of	Eisai Site #3	Busan
Korea, Republic of	Eisai Site #16	Daegu
Korea, Republic of	Eisai Site #2	Daegu
Korea, Republic of	Eisai Site #19	Daejeon
Korea, Republic of	Eisai Site #10	Gwangju
Korea, Republic of	Eisai Site #12	Gyeonggi-do
Korea, Republic of	Eisai Site #15	Gyeonggi-do
Korea, Republic of	Eisai Site #17	Gyeonggi-do
Korea, Republic of	Eisai Site #5	Gyeonggi-do
Korea, Republic of	Eisai Site #14	Incheon
Korea, Republic of	Eisai Site #1	Seoul
Korea, Republic of	Eisai Site #13	Seoul
Korea, Republic of	Eisai Site #18	Seoul
Korea, Republic of	Eisai Site #4	Seoul
Korea, Republic of	Eisai Site #6	Seoul
Korea, Republic of	Eisai Site #7	Seoul
Korea, Republic of	Eisai Site #8	Seoul
Korea, Republic of	Eisai Site #9	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Korea Inc.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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