12-Week, Double-Blind, Placebo-Controlled, Randomized Study of the Efficacy of 40 mg/Day KW-6002 in Parkinson's Disease Patients on Levodopa/Carbidopa

A 12-week, double-blind, placebo-controlled, multicenter, randomized study designed to evaluate the safety and efficacy of 40 mg/day istradefylline compared with placebo in subjects with OFF phenomena advanced PD who were treated with levodopa/carbidopa.

Inclusion criteria

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

Exclusion criteria

• Treatment with liquid levodopa/carbodopa within 4 weeks of randomization.
• Treatment with MAO inhibitors except selegiline.
• Treatment with centrally acting dopamine antagonists within 3 months (6 months for depot preparations), e.g., antipsychotic neuroleptics, metoclopramide, buspirone, amoxapine.
• Neurosurgical surgery for Parkinson's disease.
• Atypical parkinsonism or secondary parkinsonism variants.
• Diagnosis of cancer or evidence of continued cancer within 5 years of enrollment or 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.
• Current clinically relevant depression disorder.
• History of neuroleptic malignant syndrome.
• Pregnant or lactating females. Women of child-bearing potential must use reliable method of contraception.