Parkinson's Disease
Conditions
Brief summary
This is a two-arm, double-blind, placebo-controlled study.
Interventions
DRUGperampanel
2 mg/d for 14 days followed by 4 mg/d for 14 days
DRUGplacebo
Matching placebo for for 14 days followed by 4 mg/d for 14 days
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients with idiopathic PD fulfilling the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) diagnostic criteria, with a good response to levodopa. The requirement in the UKPDSBB Step 2 for prior brain imaging is at the discretion of the investigator. * Clinical diagnosis of idiopathic Parkinson's disease (patients must have at least two of the three cardinal symptoms: resting tremor, rigidity, bradykinesia) * Hoehn and Yahr Stage II to IV. * Treatment with monotherapy of levodopa plus an aromatic acid decarboxylase inhibitor (carbidopa). The carbidopa/levodopa medication should be taken at least two times daily (excluding the bedtime/night time dose) up to a maximum of eight doses daily (including the bedtime/night time dose). * Intermittent use of either liquid forms of levodopa or subcutaneous apomorphine is permitted. * Age \>30 years of age * Women who are incapable of bearing children (e.g., clinically assessed as infertile, including surgically sterile) or who are practicing effective contraception (e.g., abstinence, intrauterine device or barrier method plus hormonal method). Postmenopausal women may be recruited but must be amenorrheic for at least 1 year to be considered. Women must have a negative serum beta-human chorionic gondotrophin (β-HCG) test at the Screening Visit and a negative urine pregnancy test prior to radiotracer administration on the day of each SPECT scanning session. Women must also be willing to remain on their current form of contraception for the duration of the study. 2. In the investigator's opinion, patients are able to complete the study and are capable of giving full written informed consent.
Exclusion criteria
Patients with any one of the following will be excluded: 1. Inability or unwillingness to undergo SPECT or other study procedures 2. Pregnant or lactating women 3. Atypical or drug-induced PD 4. Current treatment with dopamine agonists, MAO or COMT inhibitors, anticholinergics 5. Patients with a past (within 1 year) or present history of psychotic symptoms requiring antipsychotic treatment. Patients may be taking antidepressant medication, however, the dose must be stable for 4 weeks prior to the Baseline Visit. Use of antipsychotic medication including clozapine and quetiapine is prohibited, even if the indication is for movement disorders. 6. Current or prior treatment (within 4 weeks prior to Baseline Visit) with pergolide, tolcapone, methyldopa, budipine, reserpine, seroquel, or the herbal dopamine agonist, Mucuna Pruriens 7. Patients with current or prior treatment (within 4 weeks prior to the Baseline Visit) with medication known to induce the enzyme cytochrome P450 3A4 8. Use of an investigational product within 4 weeks prior to randomization or patients who have participated in a previous study with perampanel 9. Patients with a past or present history of drug or alcohol abuse as per Diagnostic and Statistical Manual - 4th edition (DSM IV) criteria 10. Dementia (as defined by a MMSE score of ≤ 24) and/or fulfilling the criteria for dementia due to PD (as defined by the Diagnostic and Statistical Manual of the American Psychiatric Association - 4th Edition) 11. Clinically significant unstable medical or psychiatric illness 12. Presence of physical, mental, or social condition that precludes informed consent or interferes with careful follow-up 13. Past (within 1 year) or present history of suicidal ideation or suicide attempts 14. Elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal (ULN) 15. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastrointestinal, haematological, endocrine, or metabolic systems that might complicate assessment of the tolerability of the study medication 16. Evidence of significant active hematological disease: white blood cell (WBC) count ≤ 2500/μL; absolute neutrophil count ≤ 1000/μL 17. Patients with previous stereotactic surgery (eg, pallidotomy) for Parkinson's disease or with planned stereotactic surgery during the study period 18. Patients receiving or planning to receive (within 3 months) deep brain stimulation 19. Patients with conditions affecting the peripheral or central sensory system unless related to Parkinson's disease (such as mild sensory or pain syndromes limited to OFF periods) that could interfere with the evaluation of any such symptoms caused by the study drug 20. Patients with any condition that would make the patient, in the opinion of the investigator, unsuitable for the study 21. Patients with clinically significant ECG abnormality, including prolonged QTc (defined as QTc \> 450 msec)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Striatal [^123I]-Iodobenzamine (IBZM_ Binding Following a Single Dose Carbidopa/Levodopa Challenge for 15-hours at Baseline and Week 4 | Baseline and Week 4 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Caudate and Putamen [^123I]-IBZM Binding Following a Single Dose Carbidopa/Levodopa Challenge for 15-hours at Baseline and Week 4 | Baseline and Week 4 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perampanel A single dose carbidopa/levodopa (37.5mg/150mg PO) challenge at Baseline, followed by one 2-mg tablet/day PO of Perampanel for 14 days, then two 2-mg tablets/day (4-mg/day)PO of Perampanel for 14 days, followed by a single dose carbidopa/levodopa (37.5mg/150mg PO) challenge after 4 weeks. | 1 |
| Placebo A single dose carbidopa/levodopa (37.5mg/150mg PO) challenge at Baseline, followed by one 2-mg tablet/day PO of perampanel-matched placebo for 14 days, then two 2-mg tablets/day (4-mg/day)PO of perampanel-matched placebo for 14 days, followed by a single dose carbidopa/levodopa (37.5mg/150mg PO) challenge after 4 weeks. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Perampanel | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 1 Participants | — | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Change in Striatal [^123I]-Iodobenzamine (IBZM_ Binding Following a Single Dose Carbidopa/Levodopa Challenge for 15-hours at Baseline and Week 4
Time frame: Baseline and Week 4
Population: No data was collected because the study was terminated at the sponsor request due to low enrollment.
Secondary
Change in Caudate and Putamen [^123I]-IBZM Binding Following a Single Dose Carbidopa/Levodopa Challenge for 15-hours at Baseline and Week 4
Time frame: Baseline and Week 4
Population: No data was collected because the study was terminated at the sponsor request due to low enrollment.