Comparison of two dosages of tolcapone added to levodopa in nonfluctuating patients with PD.
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.
Suchowersky
O
O
Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Alberta, Canada.
Bailey
P
P
Pourcher
E
E
Bulger
L
L
Facciponte
G
G
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001577:Benzophenones / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols; D010300:Parkinson Disease / Q000188:drug therapy*; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D009596:Nitrophenols; D007980:Levodopa; D000077867:Tolcapone