TOLCAPONE IMPROVES MOTOR FUNCTION IN PARKINSONIAN-PATIENTS WITH THE WEARING-OFF PHENOMENON - A DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER TRIAL

We studied the new catechol-O-methyltransferase inhibitor tolcapone, 1 00 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were expe riencing the ''wearing-off'' phenomenon on levodopa therapy. After 3 m onths, patients receiving tolcapone had a significant decrease in mean daily levodopa dose requirement compared with placebo-treated patient s (p < 0.01). In patients treated with tolcapone 200 mg tid, daily ''o ff'' time, measured using patient diaries, was reduced from baseline b y 3.25 hours; this reduction was significantly different from that see n in the placebo group (p < 0.01). Moreover, the number of daily levod opa intakes was reduced significantly in each tolcapone group compared with placebo (p < 0.01). We found significant improvements in motor f unction and overall efficacy in the tolcapone groups (p < 0.01). The m ost frequent adverse events were associated with levodopa treatment. D yskinesia developed or worsened in 18% of patients receiving placebo, in 51% receiving tolcapone 100 mg tid, and in 64% receiving 200 mg tid , with most cases occurring within the first 30 days of the study. Dia rrhea was the most frequent nondopaminergic event, occurring in 14% on placebo, 13% on tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of patients withdrew because of adverse events: 15% on placebo, 17 % on tolcapone 100 mg tid, and 22% on 200 mg tid. We conclude that tol capone as an adjunct offers promise for the relief of the ''wearing-of f'' phenomenon in levodopa-treated parkinsonian patients.