Randomized, Placebo-Controlled Study of Tolcapone in Patients With Fluctuating Parkinson Disease Treated With Levodopa-Carbidopa

Objective To assess the efficacy and tolerability of the catechol- O -methyltransferase inhibitor tolcapone in reducing "off/on" fluctuations in levodopa-treated parkinsonian patients. Design A randomized, double-blind, placebo-controlled, parallel-group study. Setting Fifteen Parkinson disease clinics. Patients Two hundred fifteen referred outpatients with Parkinson disease who showed predictable end-of-dose motor fluctuations that were not controlled by a stable levodopa-carbidopa (Sinemet) regimen of at least 4 weeks' duration. Interventions In addition to their usual levodopa-carbidopa regimen, patients received placebo or tolcapone, 100 or 200 mg, 3 times daily orally for 6 weeks. Primary Outcome Measure Change in daily off/on time. Results Tolcapone, 100 and 200 mg 3 times daily, reduced off time by 2.0 and 2.5 hours per day, respectively, and increased on time by 2.1 and 2.3 hours per day, respectively ( P P Conclusions Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.