A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study.
BACKGROUND
Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD).


OBJECTIVE
To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations.


METHODS
Multicenter, randomized, placebo-controlled, double-blind, parallel-group study.


METHODS
Parkinson disease patients (N = 472) with at least 21/2 hours of daily "off" (poor motor function) time, despite optimized treatment with other anti-PD medications.


METHODS
Rasagiline, 1.0 or 0.5 mg/d, or matching placebo.


METHODS
Change from baseline in total daily off time measured by patients' home diaries during 26 weeks of treatment, percentage of patients completing 26 weeks of treatment, and adverse event frequency.


RESULTS
During the treatment period, the mean adjusted total daily off time decreased from baseline by 1.85 hours (29%) in patients treated with 1.0 mg/d of rasagiline, 1.41 hours (23%) with 0.5 mg/d rasagiline, and 0.91 hour (15%) with placebo. Compared with placebo, patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day, and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day. Prespecified secondary end points also improved during rasagiline treatment, including scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (activities of daily living in the off state and motor performance in the "on" state). Rasagiline was well tolerated.


CONCLUSIONS
Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients. In light of recently reported benefits in patients with early illness, rasagiline is a promising new treatment for PD.
D000368:Aged; D000369:Aged, 80 and over; D000855:Anorexia / Q000139:chemically induced; D000978:Antiparkinson Agents / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D015431:Weight Loss / Q000187:drug effects
D000978:Antiparkinson Agents; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D007980:Levodopa