The efficacy and safety of two dosages of tolcapone were compared in a 12-week crossover trial involving 118 nonfluctuating patients with PD on a stable dose of levodopa (L-Dopa). At trial onset, all patients received open-label tolcapone 100 mg three times daily for 4 weeks. At week 4, 116 eligible patients entered an 8-week double-blind treatment period and were randomized to receive tolcapone three times daily at either 100 mg (group 1;n = 58) or 200 mg (group 2;n = 58) until week 8, followed by the alternative tolcapone dosage until week 12. Ratings included Unified Parkinson's Disease Rating Scale (UPDRS), Schwab & England, and patient diaries, assessed at baseline and at 4, 8, and 12 weeks. At week 4, the investigator's global assessment (IGA) of efficacy showed improvement in 76% of patients. The mean total daily L-Dopa dose and mean UPDRS scores for subscales II and III decreased significantly (p < 0.001). During the double-blind treatment period, IGA showed improvements at either or both dosages in 61% of patients; further changes in other efficacy variables were minimal and were similar with both tolcapone dosages. The most frequent adverse events were dopaminergic (nausea and dyskinesia); the most frequent nondopaminergic adverse event was diarrhea. The incidence of adverse events during double-blind treatment was slightly higher with tolcapone 200 mg three times daily (33%) than with tolcapone 100 mg three times daily (24%). The authors conclude that tolcapone dosages of 100 mg three times daily and 200 mg three times daily are well tolerated and equally effective in improving function in L-Dopa-treated nonfluctuating patients with PD.
*Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta; †Faculty of Medicine, Dalhousie University, Saint John, New Brunswick; ‡Department of Neurological Sciences, Hopital de l'Enfant Jesus, Quebec City, Quebec; and §Clinical Research, Hoffman-La Roche, Mississauga, Ontario, Canada
Address correspondence and reprint requests to Oksana Suchowersky, Department of Clinical Neurosciences, Area 3, 3350 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada.