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

Lancet. 2005 Mar;365(9463):947-54. doi: 10.1016/S0140-6736(05)71083-7.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Catechol O-Methyltransferase Inhibitors
  • Catechols / administration & dosage
  • Catechols / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / prevention & control*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Humans
  • Indans / administration & dosage*
  • Indans / adverse effects
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Monoamine Oxidase Inhibitors / administration & dosage*
  • Monoamine Oxidase Inhibitors / adverse effects
  • Nitriles
  • Parkinson Disease / drug therapy*


  • Antiparkinson Agents
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Indans
  • Monoamine Oxidase Inhibitors
  • Nitriles
  • rasagiline
  • Levodopa
  • entacapone