Parkinson Disease
Conditions
Brief 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.
Interventions
DRUGSafinamide Mesilate
Safinamide Mesilate oral tablets.
Sponsors
Eisai Korea Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daily OFF Time at Week 18 | Baseline, Week 18 | 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. |
| Change From Baseline in PDQ-39 Score at Week 18 | Baseline, Week 18 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in King's Parkinson's Disease Pain Scale (KPPS) at Week 18 | Baseline, Week 18 | 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. |
| Change From Baseline in Mini-Mental State Examination (MMSE) at Week 18 | Baseline, Week 18 | 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. |
| Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating (MDS-UPDRS) Part 3 at Week 18 | Baseline, Week 18 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose of the study drug up to end of the treatment (up to Week 18) | 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. |
| Change From Baseline in Daily ON Time Without Dyskinesia at Week 18 | Baseline, Week 18 | 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. |
| Change From Baseline in MDS-UPDRS Part 4 at Week 18 | Baseline, Week 18 | 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. |
Countries
South Korea
Participant flow
Recruitment details
Participants took part in the study at 20 investigative sites in South Korea from 05 April 2022 to 25 May 2023.
Pre-assignment details
A total of 222 participants were screened, of which 21 were screen failures and 201 were enrolled and treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Safinamide Mesilate 100 mg 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. | 199 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Non-compliance with study procedures | 9 |
| Overall Study | Other | 4 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Safinamide Mesilate 100 mg |
|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 7.8 |
| Race/Ethnicity, Customized Asian | 199 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 199 Participants |
| Sex: Female, Male Female | 104 Participants |
| Sex: Female, Male Male | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 199 |
| other Total, other adverse events | 56 / 199 |
| serious Total, serious adverse events | 4 / 199 |
Outcome results
Primary
Change From Baseline in Daily OFF Time at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safinamide Mesilate 100 mg | Change From Baseline in Daily OFF Time at Week 18 | -0.8 hours |
p-value: <0.001Wilcoxon signed rank test
Primary
Change From Baseline in PDQ-39 Score at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safinamide Mesilate 100 mg | Change From Baseline in PDQ-39 Score at Week 18 | -2.7 score on a scale | Standard Deviation 10.3 |
p-value: <0.001Wilcoxon signed rank test
Secondary
Change From Baseline in Daily ON Time Without Dyskinesia at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safinamide Mesilate 100 mg | Change From Baseline in Daily ON Time Without Dyskinesia at Week 18 | 0.7 hours |
p-value: <0.001Wilcoxon signed rank test
Secondary
Change From Baseline in King's Parkinson's Disease Pain Scale (KPPS) at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safinamide Mesilate 100 mg | 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 |
p-value: 0.013Wilcoxon signed rank test
Secondary
Change From Baseline in MDS-UPDRS Part 4 at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safinamide Mesilate 100 mg | Change From Baseline in MDS-UPDRS Part 4 at Week 18 | -0.7 score on a scale | Standard Deviation 2.1 |
p-value: <0.001Wilcoxon signed rank test
Secondary
Change From Baseline in Mini-Mental State Examination (MMSE) at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safinamide Mesilate 100 mg | Change From Baseline in Mini-Mental State Examination (MMSE) at Week 18 | 0.2 score on a scale | Standard Deviation 1.7 |
p-value: 0.053Wilcoxon signed rank test
Secondary
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating (MDS-UPDRS) Part 3 at Week 18
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.
Time frame: Baseline, Week 18
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safinamide Mesilate 100 mg | 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 |
p-value: <0.001Wilcoxon signed rank test
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Safinamide Mesilate 100 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 80 Participants |
| Safinamide Mesilate 100 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 4 Participants |