Trial Outcomes & Findings for 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 (NCT NCT05312632)
NCT ID: NCT05312632
Last Updated: 2024-09-23
Results Overview
Participants received diary card and information on daily 'off' time and 'on' time was collected. At 30-minutes intervals throughout the period, the participant/caregiver recorded whether the participant was in an "on" phase, in an "on" phase with dyskinesia, in an "off" phase, or asleep. An "off" phase was defined as lack of mobility, bradykinesia, or akinesia whereas in an "on" phase, the participant functioned as well as can be expected for that participant, irrespective of whether or not he or she is having dyskinesia. The daily "off" time was defined as the mean of the total daily "off" time during the last two 24 hours dairy recording periods.
COMPLETED
PHASE4
201 participants
Baseline, Week 18
2024-09-23
Participant Flow
Participants took part in the study at 20 investigative sites in South Korea from 05 April 2022 to 25 May 2023.
A total of 222 participants were screened, of which 21 were screen failures and 201 were enrolled and treated in this study.
Participant milestones
| Measure |
Safinamide Mesilate 100 mg
Participants with parkinson's disease received 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Overall Study
STARTED
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201
|
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Overall Study
Safety Analysis Population
|
199
|
|
Overall Study
Full Analysis Population
|
196
|
|
Overall Study
COMPLETED
|
162
|
|
Overall Study
NOT COMPLETED
|
39
|
Reasons for withdrawal
| Measure |
Safinamide Mesilate 100 mg
Participants with parkinson's disease received 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
|
Overall Study
Adverse Event
|
12
|
|
Overall Study
Withdrawal by Subject
|
10
|
|
Overall Study
Lack of Efficacy
|
4
|
|
Overall Study
Non-compliance with study procedures
|
9
|
|
Overall Study
Other
|
4
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Safinamide Mesilate 100 mg
n=199 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Age, Continuous
|
63.6 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
104 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
95 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
199 Participants
n=5 Participants
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Race/Ethnicity, Customized
Not Hispanic or Latino
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199 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 18Population: The full analysis set (FAS) included participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or the Parkinson's disease questionnaire (PDQ-39) after dosing. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
Participants received diary card and information on daily 'off' time and 'on' time was collected. At 30-minutes intervals throughout the period, the participant/caregiver recorded whether the participant was in an "on" phase, in an "on" phase with dyskinesia, in an "off" phase, or asleep. An "off" phase was defined as lack of mobility, bradykinesia, or akinesia whereas in an "on" phase, the participant functioned as well as can be expected for that participant, irrespective of whether or not he or she is having dyskinesia. The daily "off" time was defined as the mean of the total daily "off" time during the last two 24 hours dairy recording periods.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=189 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Change From Baseline in Daily "OFF" Time at Week 18
|
-0.8 hours
Interval -11.2 to 3.7
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PRIMARY outcome
Timeframe: Baseline, Week 18Population: The FAS included all participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or PDQ-39 after dosing.
The PDQ-39 was a self-reported outcome or rater-reported outcome of 39 questions relating to 8 domains: mobility (Questions 1-10), activities of daily living (ADL) (Questions 11-16), emotional well-being (Questions 17-22), stigma (Questions 23-26), social support (Questions 27-30), cognition (Questions 31-33), communication (Questions 34-36) and bodily discomfort (Questions 37-39). Each question was answered on a 5-point scale from 0 (Never) to 4 (Always/Cannot Do At All). Scores were calculated by summing the answers to the questions in the domain and converting to a total score scale from 0 to 100. Higher scores were associated with the more severe symptoms of the disease such as tremor and stiffness.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=196 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Change From Baseline in PDQ-39 Score at Week 18
|
-2.7 score on a scale
Standard Deviation 10.3
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SECONDARY outcome
Timeframe: Baseline, Week 18Population: The FAS included all participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or PDQ-39 after dosing.
MDS-UPDRS rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: 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 section of scale consisted of 18 items, with 33 separate ratings being performed on scale from 0 (normal) to 4 (severe). The total score ranged from 0 to 132, with a lower score=better motor function; higher score=more severe motor symptoms.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=196 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating (MDS-UPDRS) Part 3 at Week 18
|
-1.7 score on a scale
Standard Deviation 8.4
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SECONDARY outcome
Timeframe: Baseline, Week 18Population: The FAS included all participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or PDQ-39 after dosing.
The MDS-UPDRS rating tool was used to follow longitudinal course of Parkinson's Disease. It was 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 were rated on a scale of 0 to 4. 6 items being performed on scale from 0 (normal) to 4 (severe), where the total score ranged from 0 to 24, lower score indicated better motor function and higher score indicated more severe motor symptoms.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=196 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
|
Change From Baseline in MDS-UPDRS Part 4 at Week 18
|
-0.7 score on a scale
Standard Deviation 2.1
|
SECONDARY outcome
Timeframe: Baseline, Week 18Population: The FAS included all participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or PDQ-39 after dosing.
KPPS is a Parkinson's Disease-specific pain scale that evaluated 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 was 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 which ranged from 0 to 168. Higher scores indicated more severity and frequency of pain.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=196 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Change From Baseline in King's Parkinson's Disease Pain Scale (KPPS) at Week 18
|
-1.5 score on a scale
Standard Deviation 11.3
|
SECONDARY outcome
Timeframe: Baseline, Week 18Population: The FAS included all participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or PDQ-39 after dosing.
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. Total scores ranged from 0 (most impaired) to 30 (no impairment). MMSE used to assess the severity of cognitive dysfunction, with a higher score indicating better cognitive state.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=196 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Change From Baseline in Mini-Mental State Examination (MMSE) at Week 18
|
0.2 score on a scale
Standard Deviation 1.7
|
SECONDARY outcome
Timeframe: Baseline, Week 18Population: The FAS included all participants who received at least 1 dose of study drug and had at least 1 record of daily "off" time or PDQ-39 after dosing. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
Participants received diary card and information on daily 'off' time and 'on' time was collected. At 30-minute intervals throughout the period, the participant/caregiver recorded whether the participant was in an "on" phase, in an "off" phase, or asleep. An "off" phase was defined as lack of mobility, bradykinesia, or akinesia whereas in an "on" phase, the participant functioned as well as can be expected for that participant, irrespective of whether or not he or she is having dyskinesia. The daily "on" time was defined as the sum of the time without dyskinesia during the on phase to number of days completed in the diary.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=189 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
|
Change From Baseline in Daily "ON" Time Without Dyskinesia at Week 18
|
0.7 hours
Interval -6.2 to 10.0
|
SECONDARY outcome
Timeframe: From the first dose of the study drug up to end of the treatment (up to Week 18)Population: The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
A TEAE was defined as an adverse event (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 was any untoward medical occurrence that at any dose: results in death, was life-threatening, inpatient hospitalization, requires prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), was a medically significant event.
Outcome measures
| Measure |
Safinamide Mesilate 100 mg
n=199 Participants
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
80 Participants
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|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
4 Participants
|
Adverse Events
Safinamide Mesilate 100 mg
Serious adverse events
| Measure |
Safinamide Mesilate 100 mg
n=199 participants at risk
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
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|---|---|
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Injury, poisoning and procedural complications
Cartilage injury
|
0.50%
1/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.50%
1/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.50%
1/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
General disorders
Condition aggravated
|
0.50%
1/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Infections and infestations
COVID-19
|
0.50%
1/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
Other adverse events
| Measure |
Safinamide Mesilate 100 mg
n=199 participants at risk
Participants with parkinson's disease received safinamide mesilate 50 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 was increased to 100 mg (two tablets of 50 mg each), orally, once daily for up to 18 weeks.
|
|---|---|
|
Nervous system disorders
Dyskinesia
|
5.5%
11/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Dizziness
|
2.5%
5/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Tremor
|
1.5%
3/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Dystonia
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Headache
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Injury, poisoning and procedural complications
Overdose
|
6.5%
13/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Gastrointestinal disorders
Nausea
|
2.5%
5/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Gastrointestinal disorders
Constipation
|
1.5%
3/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Gastrointestinal disorders
Vomiting
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Infections and infestations
COVID-19
|
2.5%
5/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
General disorders
Drug ineffective
|
2.0%
4/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.0%
4/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Psychiatric disorders
Delusion
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
|
Vascular disorders
Hypotension
|
1.0%
2/199 • From the first dose of the study drug up to end of the treatment (up to Week 18)
The safety analysis population included participants who received at least 1 dose of study drug and completed at least 1 post-dose safety assessment.
|
Additional Information
Serena SoYoun Kwon
Eisai Korea Inc. Medical department
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place