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
- PMID: 15766996
- DOI: 10.1016/S0140-6736(05)71083-7
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
Abstract
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.
Comment in
-
Rasagiline for motor complications in Parkinson's disease.Lancet. 2005 Mar 12-18;365(9463):914-6. doi: 10.1016/S0140-6736(05)71056-4. Lancet. 2005. PMID: 15766976 No abstract available.
Similar articles
-
Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial.Lancet Neurol. 2016 Feb;15(2):154-165. doi: 10.1016/S1474-4422(15)00336-1. Epub 2015 Dec 23. Lancet Neurol. 2016. PMID: 26725544 Clinical Trial.
-
[Rasagiline in monotherapy in patients with early stages of Parkinson's disease and in combined and adjunct therapy to levodopa with moderate and advanced stages].Rev Neurol. 2013 Jan 1;56(1):25-34. Rev Neurol. 2013. PMID: 23250679 Review. Spanish.
-
Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in Parkinson's disease.Eur J Neurol. 2011 Dec;18(12):1373-8. doi: 10.1111/j.1468-1331.2011.03512.x. Epub 2011 Sep 6. Eur J Neurol. 2011. PMID: 21895884 Clinical Trial.
-
Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease.Clin Ther. 2007 Sep;29(9):1825-49. doi: 10.1016/j.clinthera.2007.09.021. Clin Ther. 2007. PMID: 18035186 Review.
-
Rasagiline for motor complications in Parkinson's disease.Lancet. 2005 Mar 12-18;365(9463):914-6. doi: 10.1016/S0140-6736(05)71056-4. Lancet. 2005. PMID: 15766976 No abstract available.
Cited by
-
Some Novel Therapies in Parkinson's Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature.Biomedicines. 2024 Feb 29;12(3):549. doi: 10.3390/biomedicines12030549. Biomedicines. 2024. PMID: 38540162 Free PMC article. Review.
-
Efficacy and safety of adjunctive oral therapy in Parkinson's disease with motor complications: a systematic review and network meta-analysis.BMJ Neurol Open. 2024 Feb 10;6(1):e000573. doi: 10.1136/bmjno-2023-000573. eCollection 2024. BMJ Neurol Open. 2024. PMID: 38352047 Free PMC article.
-
Levodopa use in Australia: an analysis of Pharmaceutical Benefits Scheme 10% data.BMJ Neurol Open. 2024 Jan 18;6(1):e000484. doi: 10.1136/bmjno-2023-000484. eCollection 2024. BMJ Neurol Open. 2024. PMID: 38268755 Free PMC article.
-
The effect of rasagiline on swallowing function in Parkinson's disease.Heliyon. 2023 Dec 12;10(1):e23407. doi: 10.1016/j.heliyon.2023.e23407. eCollection 2024 Jan 15. Heliyon. 2023. PMID: 38187336 Free PMC article.
-
Safety comparisons among monoamine oxidase inhibitors against Parkinson's disease using FDA adverse event reporting system.Sci Rep. 2023 Nov 6;13(1):19272. doi: 10.1038/s41598-023-44142-2. Sci Rep. 2023. PMID: 37935702 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical