title: Safinamide as Add-On Therapy to Levodopa in Mid- to Late-Stage Parkinson's Disease Fluctuating Patients: Post hoc Analyses of Studies 016 and SETTLE.
abstract: BACKGROUND
  Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson's disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson's symptoms.
  
  
  OBJECTIVE
  To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson's symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE.
  
  
  METHODS
  Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with mid- to late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as "mild fluctuators" (daily OFF time ≤4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time.
  
  
  RESULTS
  Safinamide significantly increased mean ON time (with no or non-troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O-methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait.
  
  
  CONCLUSIONS
  Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies.
authors.affiliation: Department of Medical, Zambon SpA, Bresso, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cattaneo
authors.affiliation: Department of R &D, Zambon SpA, Bresso, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sardina
authors.affiliation: Department of Clinical Science and Community, Section of Medical Statistics and Biometry "GA Maccacaro", University of Milan, Italy.
authors.forename: Ermino
authors.initials: E
authors.lastname: Bonizzoni
mesh_terms: D000368:Aged; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001596:Benzylamines / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D001596:Benzylamines; D007980:Levodopa; C092797:safinamide; D000409:Alanine
keywords: MAO-B inhibitor; Parkinson’s disease; adjunct therapy; glutamate; levodopa; motor fluctuations; safinamide