BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation 
catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to 
compare the levodopa pharmacokinetic profile throughout a day driven by the COMT 
inhibition either following repeated doses of opicapone or concomitant 
administration with entacapone.
METHODS: A randomized, double-blind, gender-balanced, parallel-group study was 
performed in 4 groups of 20 healthy subjects each. Four subjects in each group 
received placebo during the entire study. Sixteen subjects in one group received 
placebo once daily for 11 days and on day 12, 200 mg entacapone concomitantly 
with each levodopa/carbidopa dose (three times separated by a 5-h interval). 
Sixteen subjects in each of the remaining three groups received respectively 25, 
50, and 75 mg opicapone once daily for 11 days and on day 12, placebo 
concomitantly with each levodopa/carbidopa dose.
RESULTS: Levodopa minimum plasma concentration (Cmin) for each 
levodopa/carbidopa dose and for the mean of all levodopa/carbidopa doses 
increased substantially with all active treatments (entacapone and opicapone) 
when compared to the control group (placebo), with values ranging from 1.7-fold 
(200 mg entacapone) to 3.3-fold (75 mg opicapone). No statistical difference was 
found for levodopa peak of systemic exposure (as assessed by maximum observed 
plasma concentration (Cmax)) between all active treatments and placebo. A 
significant increase in the levodopa extent of systemic exposure (as assessed by 
concentration-time curve (AUC)) occurred with all opicapone treatments in 
relation to placebo. No statistical difference was found for levodopa AUC when 
entacapone was compared to placebo. When compared to entacapone, both 50 and 75 
mg opicapone presented a significant increase for the levodopa AUC. All active 
treatments significantly inhibited both peak (as assessed by Emax) and extent 
(as assessed by effect-time curve (AUEC)) of the COMT activity in relation to 
placebo. When compared to entacapone, all opicapone treatments significantly 
decreased the extent (AUEC) of the COMT activity due to a long-lasting and 
sustained effect. The tolerability profile was favorable for all active 
treatments.
CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to 
entacapone, provides a superior response upon the bioavailability of levodopa 
associated to more pronounced, long-lasting, and sustained COMT inhibition. The 
tolerability profile was favorable. On the basis of the results presented in 
this study and along with the earlier pharmacology studies, it is anticipated 
that opicapone adjunct therapy at the dosages of 25 and 50 mg will provide an 
enhancement in levodopa availability that will translate into clinical benefit 
for Parkinson's disease patients.