title: A double-blind, randomized, placebo and active-controlled study of nebicapone for the treatment of motor fluctuations in Parkinson's disease.
abstract: To determine the efficacy, safety and tolerability of nebicapone, a new catechol-O-methyltransferase inhibitor for the treatment of motor fluctuations in Parkinson's disease (PD), we conducted a multicenter, randomized, 8-week double-blind, placebo- and active-controlled, parallel-group study comparing nebicapone 50 mg, 100 mg, or 150 mg, entacapone 200 mg (active control) or placebo administered concomitantly with levodopa/carbidopa or levodopa/benserazide. Two hundred and fifty-two PD patients with motor fluctuations treated with levodopa/carbidopa or levodopa/benserazide (4-8 daily doses) were enrolled and 250 patients were eligible for intention-to-treat (ITT) analysis on the basis of having at least one efficacy assessment. The primary endpoint was 8-week change from baseline in absolute "Off" time duration noted in self-scoring diaries. At 8 weeks of treatment the mean daily "Off" time decreased significantly compared to placebo for nebicapone 150 mg (-106 min; 95%CI: -192; -21) and entacapone 200 mg (-81 min; 95%CI: -142; -19). The decrease in "Off" time with nebicapone 50 mg or 100 mg did not reach statistical significance. Treatment-emergent adverse events were reported by 32% to 49% of patients in any treatment group, with no observed dose relationship in the nebicapone groups. Clinically relevant elevations in aspartate transaminase (AST) and/or alanine transaminase (ALT) were observed in 4 of 46 patients with the nebicapone 150 mg dose. The results of this study show that nebicapone 150 mg is efficacious for the treatment of motor fluctuations in PD patients. However, the risk of increasing liver transaminases and its clinically relevance deserves further evaluation.
authors.affiliation: Neurological Clinical Research Unit, Institute of Molecular Medicine, Lisbon, Portugal.
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: José-Francisco
authors.initials: JF
authors.lastname: Rocha
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.forename: Luis
authors.initials: L
authors.lastname: Almeida
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000098:Acetophenones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001545:Benserazide / Q000627:therapeutic use; D002230:Carbidopa / Q000627:therapeutic use; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D023381:Endpoint Determination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D000098:Acetophenones; D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D001545:Benserazide; D002230:Carbidopa; C433466:nebicapone