Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): A randomised, double-blind, parallel-group trial

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  • O. Rascol, Toulouse University Hospital
  • ,
  • D. J. Brooks
  • E. Melamed, Tel Aviv University Medical School
  • ,
  • W. Oertel, Philipps-Universität Marburg
  • ,
  • W. Poewe, Innsbruck University
  • ,
  • F. Stocchi, IRCCS Neuromed
  • ,
  • E. Tolosa, Universitat Pompeu Fabra, Barcelona

Background: Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. Methods: In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. Findings: 88 (13%) patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (-1·18 h rasagiline and -1·2 h entacapone vs placebo -0·4 h; p=0·0001, p<0·0001, respectively) and increased daily on-time without troublesome dyskinesia (0·85 h vs placebo 0·03 h; p=0·0005 for both). We recorded significant mean improvements in CGI scores (-0·86 rasagiline and -0·72 entacapone vs -0·37 placebo; p<0·0001, p=0·0002, respectively). Changes in UPDRS scores also significantly improved for activities of daily living during off-time (-1·71 and -1·38 vs placebo; p<0·0001, p=0·0006, respectively) and motor function during on-time (-2·94 and -2·73 vs placebo; both p<0·0001). Frequency of adverse events was similar for all treatments. Interpretation: Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

Original languageEnglish
JournalLancet
Volume365
Issue9463
Pages (from-to)947-954
Number of pages8
ISSN0140-6736
DOIs
Publication statusPublished - 12 Mar 2005
Externally publishedYes

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