title: Effect of opicapone on levodopa pharmacokinetics, catechol-O-methyltransferase activity and motor fluctuations in patients with Parkinson's disease.
abstract: OBJECTIVE
  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.
authors: Neurological Clinical Research Unit, Institute of Molecular Medicine, Lisbon, Portugal.
authors: J J
authors: JJ
authors: Ferreira
authors: J-F
authors: JF
authors: Rocha
authors: A
authors: A
authors: Falcão
authors: A
authors: A
authors: Santos
authors: R
authors: R
authors: Pinto
authors: T
authors: T
authors: Nunes
authors: P
authors: P
authors: Soares-da-Silva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001545:Benserazide / Q000008:administration & dosage; D002230:Carbidopa / Q000008:administration & dosage; D002394:Catechol O-Methyltransferase / Q000187:drug effects*; D065098:Catechol O-Methyltransferase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D010069:Oxadiazoles; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D002394:Catechol O-Methyltransferase; D002230:Carbidopa; C549349:opicapone
keywords: COMT inhibitor; Parkinson's disease; levodopa; motor fluctuations; opicapone