Parkinson's Disease
Conditions
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study of E2007 in levodopa treated Parkinson's disease patients with motor fluctuations.
Interventions
DRUG2 mg perampanel
2 mg perampanel
DRUG4 mg perampanel
4 mg perampanel
DRUGplacebo comparator
placebo comparator
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients with idiopathic Parkinson's Disease fulfilling the United Kingdom (UK) Parkinson's disease Society Brain Bank diagnostic criteria 7, with a good response to levodopa. 2. Patients must have been diagnosed with idiopathic PD at \> 30 years of age. 3. Patients must have predictable motor fluctuations of the wearing OFF type. 4. Patients must rate between II-IV on the Hoehn & Yahr scale when in an OFF state. 5. Patients must be taking optimized levodopa therapy.
Exclusion criteria
1. Pregnant or lactating women. 2. Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (eg, abstinence, intrauterine device or barrier method plus hormonal method). These patients must have a negative serum beta-human chorionic gonadotrophin (B-HCG) test at the Screening visit, and a negative urine pregnancy test at the Baseline visit (Day 0). 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 amenorrheic for at least one year to be considered of non-child bearing potential as determined by the Investigator. 3. Patients with a past or present history of drug or alcohol abuse as per Diagnostic and Statistical Manual - 4th edition (DSM IV) criteria. 4. Patients with a past (within one year) or present history of suicidal ideation or suicide attempts. 5. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastro-intestinal, hematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data) | Baseline and Week 20 | Patients described themselves in home diaries as OFF, ON without dyskinesias, ON with non troublesome dyskinesias, ON with troublesome dyskinesias, or Asleep, every 30 minutes during waking hours for 3 consecutive days prior to Baseline, Weeks 8, 10, 18, and 20. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data) | Baseline and Week 20 | Patients described themselves in home diaries every 30 minutes during waking hours for 3 consecutive days prior to Baseline, Weeks 8, 12, 16, and 20. Unified Parkinson's Disease (PD) Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of PD. 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. Range of possible total scores, 0 to 52. ON state is when medication is providing benefits to mobility, slowness, and stiffness. 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) to Week 20 (Including LOCF Data) | Baseline and Week 20 | Patients described themselves in home diaries every 30 minutes during waking hours for 3 days prior to Baseline, Weeks 8, 12, 16, and 20. UPDRS is a standardized assessment of the symptoms and signs of PD. 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) to Week 20 (Including LOCF Data) | Baseline and Week 20 | Patients described themselves in home diaries every 30 minutes during waking hours for 3 days prior to Baseline, Weeks 8, 12, 16, and 20. ON state is when medication is providing benefits to stiffness, slowness, and tremor. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening. | 250 |
| Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening. | 251 |
| Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening. | 250 |
| Total | 751 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal Laboratory Value | 0 | 0 | 3 |
| Overall Study | Adverse Event | 38 | 26 | 44 |
| Overall Study | Lack of Efficacy | 7 | 8 | 5 |
| Overall Study | Other | 3 | 7 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 9 | 9 |
| Overall Study | Withdrawal by Subject | 9 | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo | Perampanel 2mg | Perampanel 4mg | Total |
|---|---|---|---|---|
| Age, Customized <65 years | 149 Participants | 144 Participants | 147 Participants | 440 Participants |
| Age, Customized ≥ 65 years | 101 Participants | 107 Participants | 103 Participants | 311 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 4 Participants | 1 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 6 Participants | 8 Participants | 22 Participants |
| Race/Ethnicity, Customized White | 233 Participants | 239 Participants | 240 Participants | 712 Participants |
| Sex: Female, Male Female | 86 Participants | 87 Participants | 86 Participants | 259 Participants |
| Sex: Female, Male Male | 164 Participants | 164 Participants | 164 Participants | 492 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 | 111 / 250 | 110 / 251 | 144 / 250 |
| serious Total, serious adverse events | 22 / 250 | 12 / 251 | 18 / 250 |
Outcome results
Primary
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data)
Patients described themselves in home diaries as OFF, ON without dyskinesias, ON with non troublesome dyskinesias, ON with troublesome dyskinesias, or Asleep, every 30 minutes during waking hours for 3 consecutive days prior to Baseline, Weeks 8, 10, 18, and 20. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Time frame: Baseline and Week 20
Population: The Intent-to-treat (ITT) Population for diary data consisted of all subjects who were randomized to either perampanel or placebo, had taken at least 1 dose, had a valid, nonmissing Baseline diary measurement and at least 1 valid, non-missing, postbaseline diary measurement at Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data) | -0.96 Hours |
| Perampanel 2mg | Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data) | -0.93 Hours |
| Perampanel 4mg | Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data) | -0.76 Hours |
Secondary
Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data)
Patients described themselves in home diaries every 30 minutes during waking hours for 3 consecutive days prior to Baseline, Weeks 8, 12, 16, and 20. Unified Parkinson's Disease (PD) Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of PD. 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. Range of possible total scores, 0 to 52. ON state is when medication is providing benefits to mobility, slowness, and stiffness. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Time frame: Baseline and Week 20
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data) | -0.85 Scores on a scale |
| Perampanel 2mg | Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data) | -0.81 Scores on a scale |
| Perampanel 4mg | Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data) | -1.40 Scores on a scale |
Secondary
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data)
Patients described themselves in home diaries every 30 minutes during waking hours for 3 days prior to Baseline, Weeks 8, 12, 16, and 20. ON state is when medication is providing benefits to stiffness, slowness, and tremor.
Time frame: Baseline and Week 20
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data) | 0.73 Hours |
| Perampanel 2mg | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data) | 0.78 Hours |
| Perampanel 4mg | Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data) | 0.28 Hours |
Secondary
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data)
Patients described themselves in home diaries every 30 minutes during waking hours for 3 days prior to Baseline, Weeks 8, 12, 16, and 20. UPDRS is a standardized assessment of the symptoms and signs of PD. 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 and Week 20
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data) | -2.15 Scores on a Scale |
| Perampanel 2mg | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data) | -1.69 Scores on a Scale |
| Perampanel 4mg | Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data) | -3.29 Scores on a Scale |