Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal Levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study)

Objectives - To determine the efficacy and safety of the catechol-O-methyltransferase (COMT) inhibitor entacapone. used as an adjunct to levodopa. in Parkinson's disease (PD) patients. Patients and metho([ In this parallel group, randomized, double-blind Study, 301 PD patients, the majority with motor fluctuations. received entacapone (200 mg) or placebo with each daily dose of standard or controlled-release (CR) levodopa. The 24-week treatment period was followed by 2 weeks of entacapone withdrawal. Efficacy was determined by home diaries ('on' and 'off times), Unified Parkinson's Disease Rating Scale (UPDRS) and changes in levodopa dosage, and safety by adverse-event inquiry, vital signs, electro cardiography (ECG) and laboratory tests. Results - In the total population. the UPDRS activities of daily living and motor scores were significantly improved (P < 0.05) by entacapone vs placebo. In fluctuating patients, 'on' time increased (1.7 h) and 'off time decreased (1.5 h) significantly more with entacapone than with placebo (0.5 and 0.6 h, respectively, P < 0.05). and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo (P < 0.05). Entacapone benefit was lost on withdrawal. Entacapone efficacy was comparable between patients using CR and standard levodopa preparations. Increased dyskinesias (entacapone 34%, placebo 26%) and nausea (10 and 5%, respectively), mostly occurring shortly after treatment initiation, were generally managed by reducing the levodopa dose. Diarrhoea (entacapone 8%, placebo 4%) was seldom severe. There were no differences in vital signs, ECG or laboratory results. Conclusion - Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.