Comparison of two dosages of tolcapone added to levodopa in nonfluctuatingpatients with PD

The efficacy and safety of two dosages of tolcapone were compared in a 12-w eek crossover trial involving 118 nonfluctuating patients With PD on a stab le dose of levodopa (L-Dopa). At trial onset, all patients received open-la bel 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 randomiz ed 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 tol capone dosage until week 12. Ratings included Unified Parkinson's Disease R ating Scale (UPDRS), Schwab & England, and patient diaries, assessed at bas eline and at 4, 8, and 12 weeks. At week 4, the investigator's global asses sment (IGA) of efficacy showed improvement in 76% of patients. The mean tot al daily L-Dopa dose and mean UPDRS scores for subscales II and III decreas ed 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 (nau sea and dyskinesia); the most frequent nondopaminergic adverse event was di arrhea. The incidence of adverse events during double-blind treatment was s lightly higher with tolcapone 200 mg three times daily (33%) than with tolc apone 100 mg three times daily (24%). The authors conclude that tolcapone d osages of 100 mg three times daily and 200 mg three times daily are well to lerated and equally effective in improving function in L-Dopa-treated nonfl uctuating patients with PD.