Efficacy and tolerability of entacapone in patients with Parkinson's disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations. A randomized, double-blind, multicentre study

The efficacy and tolerability of entacapone was investigated in a randomized, double-blind, placebo-controlled, 3-month study of 162 patients with Parkinson's disease (PD) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations. Patients were randomized in a 3 : 2 ratio to entacapone 200 mg or placebo, administered with each dose of levodopa. Efficacy was judged on the improvement of "on" and "off" time while awake (Patient Diary and UPDRS part IV Item 39), Investigators' Global Assessment, the SF-36 Health Survey, and changes in levodopa dosages. Patients were monitored for adverse events, laboratory safety and vital signs throughout the study. Improvements in "on" time as assessed using patient diary data showed a trend in favour of entacapone, however these did not reach statistical significance. "Off" time while awake (UPDRS part IV Item 39) showed an improvement of at least one category in 36% of entacapone-treated patients, compared with 22% in the control group (p = 0.0038). The proportion of patients showing an improvement at the Investigators' Global Assessment was significantly higher (p = 0.0006) in the entacapone-treated group of patients. Also, the proportion of patients with a reduction in their daily levodopa dose was significantly higher (p = 0.02) in the entacapone group (28%) compared with placebo (13%). As expected, the most frequent adverse events were dopamine-mediated (dyskinesia: entacapone 31% versus placebo 13%), and harmless urinary discoloration. The modest increase in dyskinesias could be readily managed by levodopa down-adjustment, and, at study end there was no significant difference for the UPDRS "overall dyskinesia score" between entacapone and placebo. In conclusion, although the primary efficacy variable did not reach statistical significance, the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy.