Evaluation of the safety and tolerability of rasagiline in the treatment of the early stages of Parkinson's disease.

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).

Limitations: 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.