Long Term Study of Istradefylline in Subjects With Moderate to Severe Parkinson's Disease

Study Overview
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Brief Summary
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This is a Phase 3, 52-week, open-label, flexible-dose, multinational, multicenter study to evaluate the safety and tolerability of istradefylline 20 or 40 mg/d in subjects with moderate to severe PD with motor fluctuations and dyskinesia on levodopa combination (levodopa/carbidopa or levodopa/benserazide) therapy plus at least one adjunctive PD medication. Subjects who completed 12 weeks of double-blind treatment and the 30-day follow-up period in Study No. 6002-014 will undergo Screening and Baseline evaluations for eligibility for the study. Eligible subjects will be treated with istradefylline at a starting dose of 20 mg/d with an option for a dose adjustment to 40 mg/d at Week 12 based on the Investigator's judgment of each subject's response and tolerability. If deemed necessary, one unscheduled dose adjustment visit between Week 2 to Week 12 is allowed in accordance with clinical judgment of the Investigator. Subjects who had a dose adjustment to 40 mg/d can have their dose decreased to 20 mg/d by the Investigator at a second unscheduled dose adjustment visit if there are tolerability issues. The istradefylline dose should remain fixed between Week 26 to Week 52. Consultation with the Sponsor's Medical Monitor is required prior to any unscheduled dose adjustment visits. A subject may discontinue from the study at any time.

Official Title
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A Phase 3, Long-term, Open-label Study of Istradefylline in Subjects With Moderate to Severe Parkinson's Disease

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: Istradefylline 20 mg or 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent; Subjects who completed Study No. 6002-014 inclusive of the 30-day follow-up period; Currently taking levodopa combination (carbidopa/levodopa or benserazide/levodopa) therapy plus at least one adjunctive PD medication; Women of child-bearing potential (WOCBP) must use a reliable method of contraception and have a negative serum pregnancy test at Screening; Exclusion Criteria: Subjects with less than 70% treatment compliance throughout their enrollment on Study No 6002-014 and or with major protocol deviations in Study No. 6002-014 (subjects who failed to meet any of the inclusion criteria, subjects who met any of the exclusion criteria or subjects who met the criteria for subject withdrawal but who were not withdrawn); Subjects on apomorphine and/or dopamine receptor antagonists or direct gastrointestinal levodopa infusion; Subject who have had neurosurgical operation for PD; Subjects taking A2a antagonist, potent CYP3A4 inhibitors, potent CYP34A inducers; Subjects who have had a diagnosis of cancer or evidence of continued malignancy within the past three years (with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with normal prostate-specific antigens post resection).

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Istradefylline 20 mg or 40 mg<br>Treatment for 52 weeks | Drug: Istradefylline 20 mg or 40 mg<br>* Istradefylline 20 or 40 mg<br>* Other names: KW-6002;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the Long-term Safety and Tolerability of Oral Istradefylline (20mg or 40mg/Day [mg/d]) | The number of subjects experiencing an adverse event as well as clinical laboratory tests (chemistry, haematology and urinalysis) were collected to evaluate the safety profile of istradefylline (20mg or 40mg/day [mg/d]). | From screening through to study completion, an average of 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | The number and percentage of subjects showing improvement (moderate or mild) on PGI-I scores with Istradefylline 20 mg or 40 mg. Each subjects 'key symptom' (the symptom they had most trouble with) on the PGI-I was identified and evaluated at baseline and at Week 12, 26 and 52. In addition, the subject's overall condition and symptoms of fatigue, sleep and motivation to get things done were also evaluated at week 12, 26 and 52. Subjects rated each on a scale 1 to 5 for change from baseline status utilizing the following scale: 1= Moderate improvement (or greater) 2= Mild improvement, 3= No change from baseline, 4 = Mild deterioration, 5= Moderate deterioration (or greater). | From baseline through to study completion at week 52, plus 30 days post last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Moderate to Severe Parkinson's Disease