BACKGROUND AND PURPOSE: Opicapone (OPC) is a novel third generation 
catechol-O-methyltransferase (COMT) inhibitor that enhances levodopa 
availability. This study investigated the effects of OPC in comparison with 
placebo on levodopa pharmacokinetics, tolerability and safety, COMT activity and 
motor response to levodopa in Parkinson's disease (PD) patients with motor 
fluctuations.
METHODS: This was a randomized, multicentre, double-blind and placebo-controlled 
study in four parallel groups of PD patients treated with standard-release 
100/25 mg levodopa/carbidopa or levodopa/benserazide and with motor fluctuations 
(wearing-OFF phenomenon). Subjects were sequentially assigned to be 
administered, once-daily, up to 28 days (maintenance phase), placebo (n = 10) or 
5 (n = 10), 15 (n = 10) and 30 mg (n = 10) OPC. Two levodopa tests were 
performed, one at baseline and another following the maintenance phase. Subjects 
kept a diary to record motor fluctuations (ON/OFF periods) throughout the study.
RESULTS: In relation to placebo, levodopa exposure (AUC0-6) increased 24.7%, 
53.9% and 65.6% following 5, 15 and 30 mg OPC, respectively. Maximum COMT 
inhibition (Emax) ranged from 52% (5 mg OPC) to 80% (30 mg OPC). The study was 
not designed to detect any significant differences in motor performance, but the 
exploratory analysis performed shows improvement in various motor outcomes, 
including a dose-dependent change in absolute OFF time corresponding to a 
percentage decrease of 4.16% (P > 0.05), 29.55% (P > 0.05) and 32.71% (P < 0.05) 
with 5, 15 and 30 mg OPC, respectively. Treatments were generally well tolerated 
and safe.
CONCLUSIONS: OPC is a promising new COMT inhibitor that significantly decreased 
COMT activity, increased systemic exposure to levodopa and improved motor 
response.