Parkinson's Disease
Conditions
Brief summary
A 48-month open label multi-centered extension study to evaluate the long-term safety, tolerability and efficacy of E2007 in patients with Parkinson's Disease with wearing off motor fluctuations and on period Dyskinesias.
Interventions
DRUGPerampanel
1mg once daily for two weeks, followed by 2mg once daily for 2 weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner.
Sponsors
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients enrolled in Study E2007-E044-204 and who either completed 12 weeks of study drug treatment or who withdrew from the study due to lack of efficacy.
Exclusion criteria
* Pregnant or lactating women. * Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g. abstinence, IUD-intrauterine device, or barrier method plus hormonal method). These patients 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. * Fertile men not willing to use reliable contraception and fertile men with partners not willing to use reliable contraception. These patients and their partners must also be willing to remain using reliable contraception for the duration of the study. * Patients with a past or present history of drug or alcohol abuse. * Patients with a past (within one year) or present history of psychotic symptoms requiring antipsychotic treatment. Patients may be taking anti-depressant medication, however the dose must have been kept stable for at least 8 weeks prior to baseline visit. * Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastro-intestinal, haematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication. * Patients with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper normal limit). * Patients with current or prior treatment (within 4 weeks prior to the Baseline visit) with medication known to induce the enzyme cytochrome P450 3A4 including but not limited to; carbamazepine; dexamethasone; ethosuximide; phenobarbital; phenytoin; primidone; rifabutin; rifampicin; and St John's Wort. * Current or prior treatment (within 4 weeks prior to baseline visit) with methyldopa, budipine, reserpine or intermittent use of liquid forms of levodopa or as needed (prn) apo-morphine. * Patients with previous stereotactic surgery (e.g. pallidotomy) for Parkinson's disease or who are likely to undergo surgery for Parkinson's disease while participating in this study. * Patients receiving deep brain stimulation (DBS) or who are likely to undergo DBS for Parkinson's disease while participating in the extension study. * Patients with clinically significant cognitive impairment (mini-mental state examination (MMSE) \<24 and /or fulfilling diagnostic and statistical manual of mental disorders (DSM IV) criteria for dementia due to Parkinson's disease). * Patients with conditions affecting the peripheral or central sensory system.
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 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156 | OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. This outcome measure was based on data collected through use of a patient diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156 | ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. This outcome measure was based on data collected through use of a patient diary. |
| Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156 | 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. Range of possible total scores, 0 to 56. ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. |
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-E044-204). Subjects started on perampanel 1mg once daily for 4 weeks, followed by 2mg once daily for 2 weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. There were at least 2 weeks between each titration to assess safety and tolerability, and the subjects attended a clinic visit for safety review and dispensing of more medication. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner. | 48 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) Subjects entered this open-label extension study from the double-blind core study (E2007-E044-204). Subjects started on perampanel 1mg once daily for 4 weeks, followed by 2mg once daily for 2 weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. There were at least 2 weeks between each titration to assess safety and tolerability, and the subjects attended a clinic visit for safety review and dispensing of more medication. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner. | 134 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 34 |
| Overall Study | Lack of Efficacy | 4 | 14 |
| Overall Study | Other | 3 | 20 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Study termination by sponsor | 18 | 44 |
| Overall Study | subject withdrew consent | 13 | 23 |
Baseline characteristics
| Characteristic | Perampanel (Placebo During Core Study) | Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Total |
|---|---|---|---|
| Age, Customized <65 years | 27 Participants | 72 Participants | 99 Participants |
| Age, Customized >=65 years | 21 Participants | 62 Participants | 83 Participants |
| Race/Ethnicity, Customized Caucasian | 48 Participants | 134 Participants | 182 Participants |
| Sex: Female, Male Female | 23 Participants | 54 Participants | 77 Participants |
| Sex: Female, Male Male | 25 Participants | 80 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 48 | 0 / 134 |
| serious Total, serious adverse events | 13 / 48 | 39 / 134 |
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. This outcome measure was based on data collected through use of a patient diary.
Time frame: Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156
Population: Efficacy Population- All subjects who were in the Safety Population and for whom at least 1 postbaseline (post Week 0) efficacy assessment was made.
| 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 12 | -0.91 Hours | Standard Deviation 2.913 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 78 | -1.31 Hours | Standard Deviation 2.547 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 36 | -0.76 Hours | Standard Deviation 2.638 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 104 | -1.14 Hours | Standard Deviation 3.121 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 24 | -1.05 Hours | Standard Deviation 2.76 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 130 | -0.65 Hours | Standard Deviation 3.71 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 52 | -0.47 Hours | Standard Deviation 3.443 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 156 | -1.00 Hours | Standard Deviation 2.953 |
| Perampanel (Placebo During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 0 | -0.51 Hours | Standard Deviation 2.811 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 156 | -1.16 Hours | Standard Deviation 2.672 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 0 | -0.68 Hours | Standard Deviation 2.479 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 12 | -1.08 Hours | Standard Deviation 2.907 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 24 | -1.15 Hours | Standard Deviation 2.754 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 36 | -1.16 Hours | Standard Deviation 2.959 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 52 | -1.34 Hours | Standard Deviation 2.881 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 78 | -1.54 Hours | Standard Deviation 3.106 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 104 | -1.81 Hours | Standard Deviation 3.149 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study | Week 130 | -1.62 Hours | Standard Deviation 2.953 |
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. This outcome measure was based on data collected through use of a patient diary.
Time frame: Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156
Population: Efficacy 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 12 | 1.47 Hours | Standard Deviation 3.2 |
| 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 78 | 1.39 Hours | Standard Deviation 4.45 |
| 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 36 | 1.40 Hours | Standard Deviation 3.895 |
| 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 104 | 0.21 Hours | Standard Deviation 4.541 |
| 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 24 | 1.89 Hours | Standard Deviation 3.712 |
| 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 130 | -0.98 Hours | Standard Deviation 4.276 |
| 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 52 | 0.81 Hours | Standard Deviation 4.101 |
| 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 156 | -0.73 Hours | Standard Deviation 4.105 |
| 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 | 0.85 Hours | Standard Deviation 2.856 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 156 | 1.76 Hours | Standard Deviation 4.974 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 | 1.17 Hours | Standard Deviation 3.562 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 12 | 1.32 Hours | Standard Deviation 3.758 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 24 | 0.86 Hours | Standard Deviation 3.632 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 36 | 1.52 Hours | Standard Deviation 4.153 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 52 | 1.79 Hours | Standard Deviation 4.238 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 78 | 2.52 Hours | Standard Deviation 4.625 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 104 | 3.30 Hours | Standard Deviation 4.617 |
| Perampanel (Perampanel 0.5, 1, or 2 mg 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 130 | 1.42 Hours | Standard Deviation 4.013 |
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. Range of possible total scores, 0 to 56. ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor.
Time frame: Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156
Population: Efficacy 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 12 | 2.45 Scores on scale | Standard Deviation 6.926 |
| 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 78 | 3.64 Scores on scale | Standard Deviation 7.279 |
| 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 36 | 2.69 Scores on scale | Standard Deviation 8.177 |
| 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 104 | 6.25 Scores on scale | Standard Deviation 9.345 |
| 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 24 | 2.43 Scores on scale | Standard Deviation 7.247 |
| 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 130 | 6.05 Scores on scale | Standard Deviation 9.61 |
| 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 52 | 2.76 Scores on scale | Standard Deviation 6.947 |
| 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 156 | 5.72 Scores on scale | Standard Deviation 8.115 |
| 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 | 2.30 Scores on scale | Standard Deviation 6.36 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 156 | 4.20 Scores on scale | Standard Deviation 9.034 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 0 | 1.46 Scores on scale | Standard Deviation 7.501 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 12 | 0.36 Scores on scale | Standard Deviation 7.137 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 24 | 1.80 Scores on scale | Standard Deviation 7.912 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 36 | 2.78 Scores on scale | Standard Deviation 9.602 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 52 | 3.83 Scores on scale | Standard Deviation 9.084 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 78 | 3.43 Scores on scale | Standard Deviation 9.344 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 104 | 4.11 Scores on scale | Standard Deviation 10.999 |
| Perampanel (Perampanel 0.5, 1, or 2 mg During Core Study) | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | Week 130 | 2.77 Scores on scale | Standard Deviation 9.68 |