Parkinson's Disease
Conditions
Brief summary
This is a multicentre, open-label extension study to evaluate the long-term safety, tolerability, and efficacy of Perampanel (E2007) as an adjunctive therapy in levodopa treated PD subjects with motor fluctuations. All subjects who have completed E2007-E044-213 or E2007-G000-309 will be candidates for entering this extension trial, provided that they meet the inclusion/exclusion criteria and have completed the core study, up to and including the final efficacy visit.
Interventions
DRUGPerampanel
Sponsors
Eisai Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male or female subjects with idiopathic PD who have fulfilled the entry criteria to studies E2007-G000-309 or E2007-E044-213. Subjects must have completed the core efficacy study up to and including the final efficacy and follow up visits as applicable. Subjects with mild or moderate AEs thought to be related to Perampanel (E2007) can be entered into the study if the investigator considers it safe.
Exclusion criteria
1. Show evidence of clinically significant disease (i.e., severe cardiovascular or pulmonary disease, bronchial asthma, endocrine disease, history of peptic ulcer disease, history of myocardial infarction with residual atrial nodal or ventricular arrhythmias) that, in the opinion of the investigator, could affect either the patient's safety or the conduct of the study. 2. Pregnant or lactating women. 3. Women of childbearing potential (WOCBP) unless infertile (including surgically sterile) or practicing effective contraception (e.g., intrauterine device \[IUD\] or barrier method plus hormonal method). These subjects must have a negative urine pregnancy test at Visit 1 or 2 as indicated by entry into the study. These subjects must also be willing to remain on their current form of contraception for the duration of the study. Postmenopausal women may be recruited but must be amenorrhoeic for at least 1 year to be considered of non-child bearing potential as determined by the investigator. 4. Subjects with a past (within the past 5 years) or present history of drug or alcohol abuse as per Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM IV) criteria. 5. Antipsychotics are permitted as necessary. Subjects may be taking anti-depressant medication, however the dose must be stable for 4 weeks prior to their first study visit (the visit at which the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up | OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. All data was collected using a 3-day diary within a window of a defined visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Baseline, Week 0, Week 20, Week 32 | Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. Part II assesses activities of daily living (ADL) based on 13 items, such as speech, hygiene, and falling. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. |
| Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Baseline, Week 0, Week 20, Week 32 | Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. Part III assesses motor activity, based on 14 items, such as gait, facial expression, and rigidity. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. ON state is when medication is providing benefits to stiffness, slowness, and tremor. |
| Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up | ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. All data was collected using a 3-day diary within a window of a defined visit. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perampanel (Placebo During Core Study) Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study. | 121 |
| Perampanel (Entacapone 200mg During Core Study) Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study. | 108 |
| Perampanel (Perampanel 4mg During Core Study) Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study. | 96 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 | 4 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Study termination by sponsor | 115 | 98 | 90 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | Perampanel (Placebo During Core Study) | Perampanel (Entacapone 200mg During Core Study) | Perampanel (Perampanel 4mg During Core Study) | Total |
|---|---|---|---|---|
| Age, Customized <65 | 65 Particpants | 52 Particpants | 46 Particpants | 163 Particpants |
| Age, Customized >= 65 | 56 Particpants | 56 Particpants | 50 Particpants | 162 Particpants |
| Race/Ethnicity, Customized Asian | 29 participants | 33 participants | 31 participants | 93 participants |
| Race/Ethnicity, Customized White | 92 participants | 75 participants | 65 participants | 232 participants |
| Sex: Female, Male Female | 46 Participants | 44 Participants | 30 Participants | 120 Participants |
| Sex: Female, Male Male | 75 Participants | 64 Participants | 66 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 27 / 121 | 27 / 108 | 17 / 96 |
| serious Total, serious adverse events | 2 / 121 | 6 / 108 | 2 / 96 |
Outcome results
Primary
Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study
OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. All data was collected using a 3-day diary within a window of a defined visit.
Time frame: Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up
Population: Safety Population - All subjects entering the open-label extension study who took at least 1 dose of perampanel.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 0 | -1.03 Hours | Standard Deviation 2.635 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 2 | -0.91 Hours | Standard Deviation 2.323 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 4 | -0.65 Hours | Standard Deviation 2.945 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 8 | -0.70 Hours | Standard Deviation 2.983 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 20 | -1.34 Hours | Standard Deviation 2.972 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Follow-up | -0.77 Hours | Standard Deviation 2.983 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Follow-up | -1.61 Hours | Standard Deviation 2.435 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 0 | -1.07 Hours | Standard Deviation 2.595 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 8 | -1.16 Hours | Standard Deviation 2.509 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 20 | -1.14 Hours | Standard Deviation 1.805 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 2 | -1.28 Hours | Standard Deviation 2.867 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 4 | -1.15 Hours | Standard Deviation 2.01 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 2 | -1.31 Hours | Standard Deviation 2.779 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 4 | -1.67 Hours | Standard Deviation 2.438 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Follow-up | -0.94 Hours | Standard Deviation 2.978 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 8 | -1.36 Hours | Standard Deviation 2.324 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 0 | -1.24 Hours | Standard Deviation 2.643 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 20 | -2.11 Hours | Standard Deviation 2.163 |
Secondary
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study
ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. All data was collected using a 3-day diary within a window of a defined visit.
Time frame: Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 0 | 1.08 Hours | Standard Deviation 2.82 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 2 | 0.30 Hours | Standard Deviation 2.776 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 4 | 0.38 Hours | Standard Deviation 2.825 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 8 | 0.17 Hours | Standard Deviation 3.099 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 20 | 0.94 Hours | Standard Deviation 3.535 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Follow-up | 0.43 Hours | Standard Deviation 3.368 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Follow-up | 1.12 Hours | Standard Deviation 2.561 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 0 | 0.58 Hours | Standard Deviation 3.004 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 8 | 0.52 Hours | Standard Deviation 2.542 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 20 | 0.82 Hours | Standard Deviation 2.231 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 2 | 0.80 Hours | Standard Deviation 2.731 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 4 | 0.43 Hours | Standard Deviation 2.091 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 2 | 0.91 Hours | Standard Deviation 2.94 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 4 | 1.24 Hours | Standard Deviation 2.724 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Follow-up | 0.85 Hours | Standard Deviation 3.497 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 8 | 0.73 Hours | Standard Deviation 2.261 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 0 | 0.48 Hours | Standard Deviation 2.773 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study | Week 20 | 1.62 Hours | Standard Deviation 2.351 |
Secondary
Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study
Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. Part II assesses activities of daily living (ADL) based on 13 items, such as speech, hygiene, and falling. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Time frame: Baseline, Week 0, Week 20, Week 32
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 20 | -0.12 Scores on a scale | Standard Deviation 4.727 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 0 | -0.84 Scores on a scale | Standard Deviation 4.241 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 32 | 1.11 Scores on a scale | Standard Deviation 2.667 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 20 | -2.82 Scores on a scale | Standard Deviation 4.086 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 0 | -1.99 Scores on a scale | Standard Deviation 4.469 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 32 | 0.60 Scores on a scale | Standard Deviation 2.408 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 0 | -1.66 Scores on a scale | Standard Deviation 4.598 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 32 | -0.67 Scores on a scale | Standard Deviation 3.141 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study | Week 20 | -2.66 Scores on a scale | Standard Deviation 4.972 |
Secondary
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study
Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. Part III assesses motor activity, based on 14 items, such as gait, facial expression, and rigidity. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. ON state is when medication is providing benefits to stiffness, slowness, and tremor.
Time frame: Baseline, Week 0, Week 20, Week 32
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 20 | 0.30 Scores on a scale | Standard Deviation 7.463 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 0 | -0.25 Scores on a scale | Standard Deviation 6.874 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 32 | 2.22 Scores on a scale | Standard Deviation 5.869 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 20 | -0.53 Scores on a scale | Standard Deviation 6.95 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 0 | -0.64 Scores on a scale | Standard Deviation 6.911 |
| Perampanel (Entacapone 200mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 32 | -2.00 Scores on a scale | Standard Deviation 5.523 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 0 | -0.96 Scores on a scale | Standard Deviation 6.999 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 32 | 7.17 Scores on a scale | Standard Deviation 6.463 |
| Perampanel (Perampanel 4mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study | Week 20 | -1.63 Scores on a scale | Standard Deviation 8.005 |