Evaluation of the Long-term Safety, Tolerability, and Efficacy of Perampanel (E2007) as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Subjects With Motor Fluctuations

Study Overview
=================
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.

Official Title
-----------------
A Multi-centre, Open Label Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of Perampanel (E2007) as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Subjects With Motor Fluctuations

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: Perampanel


Participation Criteria
=================
Eligibility Criteria
-----------------
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: 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. Pregnant or lactating women. 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. 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. 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 exclusion criteria are done with the patient). Subjects with a past (within one year) or present history of major depression, suicidal ideation, or suicide attempts. Subjects 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. Subjects with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper limit of the normal range). Subjects with current or prior treatment (within 4 weeks prior to the Screening Visit) with medication known to induce the enzyme CYP3A4. Clinically significant ECG abnormality, and/or prolonged QTc (defined as QTc ≥ 450 msec). Current or prior treatment (within 4 weeks prior to entry visit) with tolcapone, methyldopa, budipine, or reserpine. Subjects with previous stereotactic surgery (e.g., pallidotomy) for PD or with planned stereotactic surgery during the study period Subjects receiving or with planned (next 12 months) deep brain stimulation. Subjects with conditions affecting the peripheral or central sensory system unless related to PD (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 medication. Subjects have received an investigational product (other than E2007 or entacapone 200 mg) within 4 weeks prior to Screening Any condition that could, in the opinion of the investigator, place the subject at increased risk or is likely to prevent completion of the study. Subjects with any condition that would make the subject, in the opinion of the investigator, unsuitable for the study. Patients on pergolide or cabergoline.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E2007<br>E2007 2 mg (one 2 mg tablet taken daily in the evening), or 4 mg (two 2 mg tablets daily in the evening). | Drug: Perampanel<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 0, Week 20, Week 32 | 
| 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. | Baseline, Week 0, Week 20, Week 32 | 
| 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. | Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up |