title: Evaluation of the safety and tolerability of rasagiline in the treatment of the early stages of Parkinson's disease.
abstract: OBJECTIVE
  Rasagiline is a second-generation, irreversible MAO-B inhibitor (MAOB-I) previously shown to be efficacious and well-tolerated compared to placebo in the treatment of early Parkinson's disease (PD). ACTOR (ACceptabilité TOlérance Rasagiline) was a 15-week, multi-center, randomized, double-blind study aimed to assess the safety and tolerability of rasagiline compared to the dopaminergic agonist pramipexole in the treatment of early PD.
  
  
  METHODS
  Patients with early, untreated idiopathic PD were randomized to receive 1 mg rasagiline (n = 53) or 1.5 mg pramipexole (n = 56) daily. The primary outcome was the number of patients experiencing a 'clinically important adverse event' (classified as a serious adverse event, an event leading to withdrawal or severe according to the patient). Safety outcomes were evaluated by the investigator and the patient. Analysis of the primary criterion was a comparative analysis using the chi-squared test. The Wilcoxon Mann-Whitney test was conducted to test the severity of patient-reported adverse events. Other tests performed include a covariance analysis and Student's t-tests.
  
  
  RESULTS
  Mean disease duration was 3.4 months, and mean age was 62.6 years. Of patients taking pramipexole, 44.6% reported at least one 'clinically important' adverse event compared to 32.1% of patients taking rasagiline; non-inferiority of rasagiline was reached, with a difference in proportions of -12.6% [confidence interval of -27.8%; 2.6%]. There were no significant differences in clinical effectiveness between the treatments, measured by clinical and patient global impression of improvement (CGI-I, PGI-I) and PDQ-8 scales. A significant decrease in the incidence of gastrointestinal symptoms (p = 0.015) and sleep disorders (p = 0.027) was reported by physicians in the rasagiline group compared to the pramipexole group; the propensity to sleepiness improved significantly in the rasagiline group (p = 0.020), and worsened in the pramipexole group (p = 0.042).
  
  
  CONCLUSIONS
  Limitations of this study include the limited sample size due to the lower than anticipated recruitment and the accidental inclusion of a patient who had taken contraindicated medication.
  
  
  CONCLUSIONS
  In this study, the safety profile of rasagiline had clinically favorable differences in gastrointestinal and sleep adverse events compared to pramipexole, whilst showing comparable clinician and patient-rated clinical effectiveness as a monotherapy for the treatment of early idiopathic PD.
authors.affiliation: Centre Hospitalier du Pays d’Aix, Aix-en-Provence, France.
authors.forename: François
authors.initials: F
authors.lastname: Viallet
authors.forename: Séverine
authors.initials: S
authors.lastname: Pitel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lancrenon
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects; D052160:Benzothiazoles / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D012893:Sleep Wake Disorders / Q000139:chemically induced; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D000077487:Pramipexole