Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in dailymedical practice: An open, multicenter study

Entacapone is a potent, reversible and orally active inhibitor of catechol- O-methyltransferase. This open multicenter study evaluated the efficacy, sa fety and tolerability of entacapone as adjunct therapy to levodopa/dopa dec arboxylase inhibitor(greater than or equal to 3 daily doses) in patients wi th idiopathic Parkinson's disease and end-of-dose motor fluctuations. The 8 -week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone adm inistered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at leas t 1 month. The primary efficacy criteria were: (1) Part it (activities of d aily living, ADL) of the Unified Parkinson's Disease Rating Scale (UPDRS), (2) the reduction of 'off' time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary out come measures included: (1) the inv estigator's global assessment of change, (2) quality of life (QoL) was asse ssed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in 'off' time during the waking period; this impro vement was highly significant(p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.0 01), except social support and cognition. This improvement was statisticall y significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreas ed significantly from 2.3 to 2.1 from baseline to end of study Ip < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adve rse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study sug gests that the benefits of entacapone are associated with a significant imp rovement in QoL. Copyright (C) 2001 S. Karger AG,Basel.