12-Week, Double-Blind, Placebo-Controlled Study of 20 and 60 mg/Day Istradefylline in Parkinson's Disease Patients on Levodopa/Carbodopa

Inclusion criteria

• United Kingdom Parkinson's Disease Society brain bank diagnostic criteria (Steps 1 and 2).
• Modified Hoehn and Yahr in the OFF state of II-IV.
• Treated with levodopa/carbidopa for at least one year with a stable regimen for 4 weeks prior to randomization.
• Taking at least 4 doses of levodopa/carbidopa per day (3 doses if at least 2 doses contained slow-release formulation) with predictable end of dose wearing off.
• Successfully competed Parkinson's disease patient diary training with at least 120 minutes of OFF time per day.
• Stable regimen of other antiparkinson's medications for 4 weeks prior to randomization.
• At least 30 years of age and able to give written informed consent.

Exclusion criteria

• Treatment with liquid levodopa/carbidopa within 4 weeks of randomization.
• Treatment with MAO inhibitors except selegiline.
• Treatment within 3 months with centrally acting dopamine antagonists (6 months for depot formulations), e.g., antipsychotic neuroleptics, metoclopramide, buspirone, amoxapine.
• Neurosurgical operation for Parkinson's disease.
• Atypical parkinsonism or secondary parkinsonism variants.
• Diagnosis of cancer or evidence of continued disease within 5 years.
• Clinically significant illness of any organ system (e.g., ALT or AST > 1.5 times the upper limit of normal).
• Mini-Mental Status Examination score of 25 or less.
• History of drug or alcohol abuse or dependence within 2 years.
• History of psychotic illness or seizures.
• Clinically relevant depression disorder.
• History of neuroleptic malignant syndrome.
• Pregnancy or lactation. Women of child bearing potential must use a reliable method of contraception.