TY - JOUR
T1 - Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy
T2 - A randomised, placebo-controlled trial
AU - Poewe, Werner
AU - Seppi, Klaus
AU - Fitzer-Attas, Cheryl J.
AU - Wenning, Gregor K.
AU - Gilman, Sid
AU - Low, Phillip A.
AU - Giladi, Nir
AU - Barone, Paolo
AU - Sampaio, Cristina
AU - Eyal, Eli
AU - Rascol, Olivier
N1 - Funding Information:
This study was funded by Teva Pharmaceutical Industries and H Lundbeck A/S (Denmark). We thank the study investigators, Michael Schocke (Department of Radiology, Innsbruck Medical University) for assistance in the MRI substudy analysis, Elijahu Berkovich (Teva Pharmaceutical Industries), and Anita Chadha-Patel (ACP Clinical Communications, funded by Teva Pharmaceutical Industries) for medical writing support (literature searching, referencing, and editing).
Funding Information:
WP has received consulting fees from Teva, Boehringer Ingelheim, Genzyme, Solvay, and Novartis; lecture fees from Teva, Boehringer Ingelheim, Novartis, UCB, and Orion; and grant support from Boehringer Ingelheim and AstraZeneca. KS has received honoraria or consulting fees from AstraZeneca, Teva, UCB, Boehringer Ingelheim, Lundbeck, AOP Orphan Pharmaceuticals AG, Novartis, and the Movement Disorder Society, and grant support from Medical University Innsbruck, Oesterreichische Nationalbank, FWF Austrian Science Fund, the Michael J Fox Foundation, the Movement Disorder Society, and Boehringer-Ingelheim. CJF-A was previously employed by Teva Pharmaceutical Industries. GKW has received consulting or lecture fees from Affiris, AstraZeneca, Boehringer Ingelheim, Ever Pharma, Lundbeck, Neuropore, Orion, and UCB, and grant support from Medical University Innsbruck, Oesterreichische Nationalbank, FWF Austrian Science Fund, US MSA Coalition, Affiris, AstraZeneca, and Boehringer Ingelheim. NG served as the chairman of the safety committee of this study (data and safety monitoring board); he reviewed the safety measures of the protocol for completeness and adequacy before the protocol was finalised and joined the writing committee after study end; and was paid for his role by Teva Pharmaceutical Industries; serves on the International Advisory Board of Teva and Lundbeck in relation to rasagiline development and marketing; and has received honoraria, educational grants, and travel grants from Teva Pharmaceutical Industries. PB received grants from Lundbeck during the conduct of the study; and personal fees from Lundbeck, UCB, and Otsuka, and grants from Zambon, outside the submitted work. CS has received personal fees from AbbVie, Alkermes, AstraZeneca, Avanir, Biogen, Bristol-Myers Squibb, Chelsea, GlaxoSmithKline, Kyowa, Eli Lilly, Lundbeck, Neuroderm, Neurotrope, Otsuka, Pfizer, Roche, Sanofi, Servier, Shire, Takeda, and Teva, outside the submitted work. EE is employed by Teva Pharmaceutical Industries. OR has received consulting fees from GSK, Osmotica, Novartis, Schering-Plough, Boehringer Ingelheim, Abbott, and Teva and Lundbeck; lecture fees from Novartis, Boehringer Ingelheim, and Teva and Lundbeck; and grant support from Boehringer Ingelheim, GlaxoSmithKline, and Teva and Lundbeck. SG and PAL declare no competing interests.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015
Y1 - 2015
N2 - Background: Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. Methods: We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. Findings: We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). Interpretation: In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. Funding: Teva Pharmaceutical Industries and H Lundbeck A/S.
AB - Background: Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. Methods: We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. Findings: We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). Interpretation: In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. Funding: Teva Pharmaceutical Industries and H Lundbeck A/S.
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U2 - 10.1016/S1474-4422(14)70288-1
DO - 10.1016/S1474-4422(14)70288-1
M3 - Article
C2 - 25498732
AN - SCOPUS:84922568155
VL - 14
SP - 145
EP - 152
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4422
IS - 2
ER -