A Randomized, Double-Blind, Placebo-Controlled Trial of Safinamide as Add-on Therapy in Early Parkinson's Disease Patients

被引:95
作者
Stocchi, Fabrizio [1 ]
Borgohain, Rupam [2 ]
Onofrj, Marco [3 ]
Schapira, Anthony H. V. [4 ]
Bhatt, Mohit [5 ]
Lucini, Valentina [6 ]
Giuliani, Rodolfo [6 ]
Anand, Ravi [7 ]
机构
[1] IRCCS San Raffaele, Dept Neurosci, I-00163 Rome, Italy
[2] Nizams Inst Med Sci, Dept Neurol, Hyderabad, Andhra Pradesh, India
[3] Chieti Pescara Univ, Dept Neurol, Chieti, Italy
[4] UCL Inst Neurol, Dept Clin Neurosci, London, England
[5] Movement Disorder Clin, Bombay, Maharashtra, India
[6] Newron Pharmaceut, Dept Dev, Milan, Italy
[7] APC, St Moritz, Switzerland
关键词
safinamide; Parkinson's disease; add-on; motor function; alpha-aminoamide; dopamine; B INHIBITION; LEVODOPA; DYSKINESIAS; PRAMIPEXOLE; ROPINIROLE; 5-YEAR;
D O I
10.1002/mds.23954
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Safinamide is an alpha-aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add-on to dopamine agonist (DA) therapy in early-stage PD. In this 24-week, double-blind study, patients with early PD receiving a stable dose of a single DA were randomized to once-daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty-nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were -3.90 for safinamide 200 mg, -6.0 for safinamide 100 mg and -3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: -0.4; 95% confidence interval (CI): -2.3-1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: -1.9; 95% CI: -3.7 to -0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation. (C) 2011 Movement Disorder Society
引用
收藏
页码:106 / 112
页数:7
相关论文
共 20 条
[1]  
[Anonymous], PARK DIS DIAGN MAN P
[2]  
Bonuccelli Ubaldo, 2006, Expert Rev Neurother, V6, P81, DOI 10.1586/14737175.6.1.81
[3]   Safinamide: Beyond MAO-B inhibition [J].
Caccia, C. ;
Salvati, P. ;
Rossetti, S. ;
Anand, R. .
PARKINSONISM & RELATED DISORDERS, 2007, 13 :S99-S99
[4]   Safinamide - From molecular targets to a new anti-Parkinson drug [J].
Caccia, C. ;
Maj, R. ;
Calabresi, M. ;
Maestroni, S. ;
Faravelli, L. ;
Curatolo, L. ;
Salvati, P. ;
Fariello, R. G. .
NEUROLOGY, 2006, 67 (07) :S18-S23
[5]   Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition [J].
Cattaneo, C ;
Caccia, C ;
Matzo, A ;
Maj, R ;
Fariello, RG .
CLINICAL NEUROPHARMACOLOGY, 2003, 26 (04) :213-217
[6]   Impact of pramipexole on the onset of levodopa-related dyskinesias [J].
Constantinescu, Radu ;
Romer, Megan ;
McDermott, Michael P. ;
Kamp, Cornelia ;
Kieburtz, Karl .
MOVEMENT DISORDERS, 2007, 22 (09) :1317-1319
[7]   A RATING SCALE FOR DEPRESSION [J].
HAMILTON, M .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1960, 23 (01) :56-62
[8]  
Holloway RG, 2004, ARCH NEUROL-CHICAGO, V61, P1044
[9]   Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society- European Section. Part I: Early (uncomplicated) Parkinson's disease [J].
Horstink, M. ;
Tolosa, E. ;
Bonuccelli, U. ;
Deuschl, G. ;
Friedman, A. ;
Kanovsky, P. ;
Larsen, J. P. ;
Lees, A. ;
Oertel, W. ;
Poewe, W. ;
Rascol, O. ;
Sampaio, C. .
EUROPEAN JOURNAL OF NEUROLOGY, 2006, 13 (11) :1170-1185
[10]   Effects of Expectation on Placebo-Induced Dopamine Release in Parkinson Disease [J].
Lidstone, Sarah C. ;
Schulzer, Michael ;
Dinelle, Katherine ;
Mak, Edwin ;
Sossi, Vesna ;
Ruth, Thomas J. ;
de la Fuente-Fernandez, Raul ;
Phillips, Anthony G. ;
Stoessl, A. Jon .
ARCHIVES OF GENERAL PSYCHIATRY, 2010, 67 (08) :857-865