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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 12-18; 365(9463):947-54.Lct

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.

Authors+Show Affiliations

Clinical Investigation Centre, Department of Clinical Pharmacology, University Hospital, Toulouse, France. rascol@cict.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15766996

Citation

Rascol, O, et al. "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 (London, England), vol. 365, no. 9463, 2005, pp. 947-54.
Rascol O, Brooks DJ, Melamed E, et al. 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;365(9463):947-54.
Rascol, O., Brooks, D. J., Melamed, E., Oertel, W., Poewe, W., Stocchi, F., & Tolosa, E. (2005). 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 (London, England), 365(9463), 947-54.
Rascol O, et al. 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 12-18;365(9463):947-54. PubMed PMID: 15766996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Rascol,O, AU - Brooks,D J, AU - Melamed,E, AU - Oertel,W, AU - Poewe,W, AU - Stocchi,F, AU - Tolosa,E, AU - ,, PY - 2005/3/16/pubmed PY - 2005/4/9/medline PY - 2005/3/16/entrez SP - 947 EP - 54 JF - Lancet (London, England) JO - Lancet VL - 365 IS - 9463 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/15766996/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)71083-7 DB - PRIME DP - Unbound Medicine ER -