title: Rasagiline adjunct therapy in patients with Parkinson's disease: post hoc analyses of the PRESTO and LARGO trials.
abstract: BACKGROUND
  Rasagiline was safe and effective when used as adjunct therapy with levodopa in patients with moderate-to-advanced Parkinson's disease (PD) in the phase III PRESTO and LARGO studies.
  
  
  OBJECTIVE
  To assess clinical effects of rasagiline 1 mg/day on cardinal PD symptoms and motor fluctuations in defined patient subgroups using pooled data from PRESTO and LARGO.
  
  
  METHODS
  Both double-blind, randomized, and placebo-controlled studies included PD patients with motor fluctuations despite optimized therapy with levodopa, with or without concomitant dopamine agonists (DA) or catechol-O-methyltransferase inhibitor (COMT-I) treatment. These post hoc analyses measured effects of rasagiline 1 mg vs placebo on individual cardinal PD symptoms during ON time and mean change from baseline in daily OFF time in subgroups of patients who at baseline were receiving only levodopa, were considered "mild fluctuators" (daily OFF time ≤ 4 h), and who were or were not receiving concomitant DA or COMT-I therapy.
  
  
  RESULTS
  Compared with placebo, rasagiline significantly improved all cardinal PD symptoms and significantly reduced adjusted mean daily OFF time when used as first adjunct therapy in levodopa-treated patients and in patients with mild motor fluctuations. Significant improvement in motor fluctuations was reported with rasagiline regardless of concomitant DA or COMT-I use. Overall incidence of dopaminergic adverse events did not increase with concomitant DA or COMT-I use.
  
  
  CONCLUSIONS
  Rasagiline was an effective first adjunct therapy in levodopa-treated patients; benefited patients with signs of early "wearing off"; improved all cardinal PD symptoms; and further improved symptoms in patients already receiving other adjunctive dopaminergic treatment.
authors.affiliation: Department of Neurology, University of Toledo College of Medicine, Toledo, OH 43614, USA. Electronic address: lawrence.elmer@utoledo.edu.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Elmer
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage; D065098:Catechol O-Methyltransferase Inhibitors; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline
keywords: Agonist; Bradykinesia; Entacapone; Fluctuation; Parkinson; Rasagiline