The Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations

Study Overview
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Brief Summary
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Patients will be randomised to receive either placebo or the study drug for a period of 30 weeks, in addition to their standard Parkinsonian medications. During the first 8 weeks, the patient's levodopa doses may be adjusted if necessary by the investigator. For the remainder of the 22 weeks, all medications should be kept stable. Patients will be required to attend the clinic twice during the screening period and then a further 8 times during the treatment period. They will be required to complete home diaries where they will record their motor function. In addition, their doctor will assess their Parkinson's disease during the clinic visits. There will also be blood draws for safety and pharmacokinetic and pharmacogenomics evaluation. Following the treatment and assessment period, they will return to the clinic one month later for follow up.

Official Title
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A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel Group Study of the Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With 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: Male or female patients with idiopathic PD fulfilling the (UK) Parkinson's disease Society Brain Bank diagnostic criteria, with a good response to levodopa. Patients must have been diagnosed with idiopathic PD at >= 30 years of age. Patients must have predictable motor fluctuations of the wearing OFF type with the presence of at least 2 hours of OFF time during the waking day (excluding the morning OFF time) as evidenced by diary cards completed at screening and confirmed by diary data collected at the baseline visit. Before patients are randomised they must be able to show that they are able to accurately complete the diary cards. During the diary-training period at the initial screening visit there must be diary evidence of at least one transition of OFF to ON or from ON to OFF and patients must show 75% concordance with Investigator's completion of the diary card. Patients must rate between II-IV on the Hoehn & Yahr scale when in an OFF state. Patients must be taking optimised levodopa therapy (according to investigator's opinion) at least 3 times during the waking day (not including bedtime/night time dose) up to a maximum of 8 doses daily (includes bedtime/night time dose). Patients who are treated with dopamine agonists, COMT inhibitors or MAOB inhibitors and other anti-PD drugs must be on optimised and stable doses for at least 4 weeks prior to initial screening visit and must remain stable throughout the study. Only levodopa dosage can be adjusted downwards in the first 8 weeks of the double-blind treatment phase. In the Investigator's opinion patients must be able to distinguish their own motor states and the absence or presence of troublesome or non-troublesome dyskinesias. In the Investigator's opinion patients are able to complete the study including the completion of the home diary cards and capable of giving full written informed consent. EXCLUSION CRITERIA: Pregnant or lactating women. Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g., abstinence, IUD or barrier method plus hormonal method). These patients must have a negative serum B-HCG test at the initial screening visit (Visit 1), and a negative urine pregnancy test at the Baseline visit (Visit 3). 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 as determined by the investigator. Fertile men not willing to use reliable contraception and fertile men with partners not willing to use reliable contraception. Patients with a past or present history of drug or alcohol abuse as per DSM IV criteria. 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 be stable for 4 weeks prior to the baseline visit. Use of anti-psychotic medication including clozapine and quetiapine is prohibited even if the indication is for movement disorders. Patients with a past (within one year) or present history of suicidal ideation or suicide attempts. 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. Current or prior treatment (within 4 weeks prior to the baseline visit) with tolcapone, methyldopa, budipine, reserpine, seroquel or intermittent use of either liquid forms of levodopa or subcutaneous apomorphine. Patients with previous stereotactic surgery (eg 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 who have received an investigational product within 4 weeks prior to the screening visit or patients that have participated in a previous study with E2007. Patients with clinically significant cognitive impairment (MMSE <24 and /or fulfilling DSM IV criteria for dementia due to Parkinson's disease). 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.

Ages Eligible for Study
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Minimum Age: 30 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: E2007|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient diaries: Change from baseline to final efficacy visit in the mean total daily OFF time (hr). |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on average OFF time over total treatment period; UPDRS Part II: OFF state; UPDRS Part III: ON state; change from baseline to final efficacy visit in mean total daily ON time w/o dyskinesias or with no troublesome dyskinesias. |  |  |