Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations

In this 12-week, randomized. open-label, blinded-rater. parallel-group tria l, the efficacy. safety, and tolerability of tolcapone and pergolide were c ompared in parkinsonian patients with a fluctuating response to levodopa. P atients received tolcapone 100 mg three times daily (t.i.d.). with a possib le increase to 200 mg t.i.d.. or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patie nts, Efficacy variables that decreased from baseline to week 12 with tolcap one and pergolide included "off" time (reduced by 2-3 hours/day), daily lev odopa intake, sickness impact profile scores, Parkinson's disease questionn aire (PDQ)-39 scores. and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which wer e significantly greater with tolcapone the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone. re spectively. Improvements in the investigator's global assessment (IGA) of o verall efficacy were recorded in 86% of tolcapone-treated patients and in 7 8% of pergolide-treated patients. The proportion of patients who withdrew b ecause of adverse events was higher in the pergolide group (15%) than in th e tolcapone group (5%). Confusion, hypotension. nausea, constipation, abdom inal pain. and dyspepsia occurred more frequently with pergolide, whereas d iarrhea and urine discoloration occurred more frequently with tolcapone. To lcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tol capone and pergolide provided improvements in motor fluctuations and allowe d reductions in levodopa intake when added to levodopa therapy, intent to t reat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of life, was better tolerated, and had a more favorable adverse-eve nt profile than pergolide. (C) 2001 Movement Disorder Society.