Replacing a dopamine agonist by the COMT-inhibitor tolcapone as an adjunct to L-dopa in the treatment of Parkinson's disease: a randomized, multicenter, open-label, parallel-group study.
ABSTRACT This study investigated the feasibility, safety, and potential benefit in motor symptom control when switching from a dopamine agonist to tolcapone as an adjunctive therapy in patients with Parkinson's disease with a fluctuating response to levodopa (l-dopa). We determined the efficacy of 2 replacement strategies.
In this 10-week, randomized, open-label, stratified, parallel-group trial, 150 patients on a stable regimen of l-dopa/decarboxylase inhibitor in combination with bromocriptine, lisuride, or pergolide were switched to tolcapone. Primary end point was the change in daily "off" time from baseline to the end of week 10 as assessed by patient "on-off" diaries. Patients had their respective dopamine agonist reduced and finally withdrawn either by day 6 (short-term replacement, n = 72) or by day 23 (long-term replacement, n = 78).
At week 10, a significant reduction from baseline in daily "off" time (-15.9 +/- 19.3%; P < 0.001) and a significant increase of "on" time (14.6 +/- 19.8%; P < 0.001) were observed. Other efficacy variables (Unified Parkinson's Disease Rating Scale II, III, and IVb and Investigator's Global Assessment scores) improved significantly after switching to tolcapone. In general, there was no significant difference between the 2 replacement strategies. Treatment was better tolerated after the switch to tolcapone according to the IGA of tolerability.
Tolcapone, in principle, seems to be an alternative adjunct for patients, who fail to receive sufficient benefit from a dopamine agonist, for example, in case they do not tolerate an increase in dose or have unacceptable side effects. The switch from a dopamine agonist to tolcapone can be done safely within a few days.