HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.

AbstractBACKGROUND:
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.
AuthorsO Rascol, D J Brooks, E Melamed, W Oertel, W Poewe, F Stocchi, E Tolosa, LARGO study group
JournalLancet (London, England) (Lancet) 2005 Mar 12-18 Vol. 365 Issue 9463 Pg. 947-54 ISSN: 1474-547X [Electronic] England
PMID15766996 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Indans
  • Monoamine Oxidase Inhibitors
  • Nitriles
  • rasagiline
  • Levodopa
  • entacapone
Topics
  • Administration, Oral
  • Aged
  • Antiparkinson Agents (administration & dosage, adverse effects)
  • Catechol O-Methyltransferase Inhibitors
  • Catechols (administration & dosage, adverse effects)
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Dyskinesia, Drug-Induced (etiology, prevention & control)
  • Enzyme Inhibitors (administration & dosage, adverse effects)
  • Humans
  • Indans (administration & dosage, adverse effects)
  • Levodopa (administration & dosage, adverse effects)
  • Monoamine Oxidase Inhibitors (administration & dosage, adverse effects)
  • Nitriles
  • Parkinson Disease (drug therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: