A Study of E2007 In Patients With Parkinson's Disease

Study Overview
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Brief Summary
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Phase IIb open-label extension study for patients with Parkinson's Disease. All patients will receive active study drug. The study will involve outpatient visits only. Patients who completed Study E2007-A001-214 (Cohorts I and II) and who meet inclusion/exclusion criteria will be enrolled and enter the 12-week Titration Phase (from Dispense Study Drug at Week 0 [Visit 2] through Week 12 [Visit 7]) followed by the Maintenance Phase (from Week 12 [Visit 7] to end of study).

Official Title
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A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of E2007 In Patients With Parkinson's Disease Who Experience End-of-Dose Wearing-Off Motor Fluctuations

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: E2007


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA 1. Male or female patients with idiopathic Parkinson's disease who have fulfilled the entry criteria for E2007-A001-214 and have completed that study up to and including the end of treatment (Day 70) visit and the Follow-up Visit at Day 91. EXCLUSION CRITERIA Pregnant or lactating women. Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g., intrauterine device or barrier method plus hormonal method). These patients must have a negative serum beta human chorionic gonadotropin (B-HCG) test at the initial visit (Visit 1) and urine pregnancy tests throughout the study. 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 nonchildbearing potential as determined by the investigator. Patients who withdrew from Study 214 prior to the final efficacy visit for any reason, including lack of efficacy. Patients with serious adverse events in Study 214 that are either ongoing or that are possibly or probably related to the study drug. Patients with ongoing adverse events from Study 214 thought to be related to E2007. Patients with a past (within the past 5 years) or present history of drug or alcohol abuse as per the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV). Patients with a past (within 1 year) or present history of psychotic symptoms requiring antipsychotic treatment. Patients with a past (within 1 year) or present history of suicidal ideation or suicide attempts. Patients with active hepatic disease, significantly reduced hepatic function or significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper limit of the normal range). Patients with clinically significant ECG abnormality, including prolonged QTc (defined as QTc >= 450 msec using Fridericia's correction). Patients with clinically significant cardiovascular, metabolic, respiratory, renal, endocrinological, gastrointestinal diseases, psychiatric disorders, and bacterial or viral infections within the previous 30 days. Patients who are currently taking medications known to induce the enzyme cytochrome P450 3A4. Patients with current or prior treatment (within 4 weeks before entry visit) with tolcapone, methyldopa, budipine, reserpine, seroquel, or intermittent use of either liquid forms of levodopa or subcutaneous apomorphine. Patients with previous stereotactic surgery (e.g., pallidotomy) for Parkinson's disease or with planned stereotactic surgery during the study period. Patients receiving or with planned (next 6 months) deep brain stimulation. 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. Patients with any condition that would make the patient, in the opinion of the investigator, unsuitable for the study. Patients who have received an investigational product (other than E2007) within 4 weeks before screening. Patients with clinically significant cognitive impairment (mini-mental state examination [MMSE] <24 or fulfilling DSM IV criteria for dementia due to Parkinson's disease). Patients with any condition that could, in the opinion of the investigator, place the patient at increased risk or is likely to prevent completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: E2007<br>* E2007 2mg tablets. Dose (2mg, 4mg, 6mg or 8mg), is taken orally at nighttime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline by Visit in Absolute 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. | Baseline, Week 12, Week 20, Week 32, Week 44, Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline by Visit in Absolute ON Time (Without Dyskinesias or With Nontroublesome 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. | Baseline, Week 12, Week 20, Week 32, Week 44, Week 56 | 
| Mean Change From Baseline by Visit in UPDRS Part II (ADL) in OFF State (Hours) During Open-label Extension Study | 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. | Baseline, Week 12, Week 20, Week 32, Week 44, Week 56 | 
| Mean Change From Baseline by Visit in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study | The 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. | Baseline, Week 12, Week 20, Week 32, Week 44, Week 56 |