Safety and Tolerability of Pardoprunox, a New Partial Dopamine Agonist, in a Randomized, Controlled Study of Patients with Advanced Parkinson’s DiseaseHauser R.A.a · Bronzova J.b · Sampaio C.c · Lang A.E.d · Rascol O.e · Theeuwes A.b · van de Witte S.V.b
aUniversity of South Florida, Tampa, Fla., USA; bSolvay Pharmaceuticals B.V., Weesp, The Netherlands; cLaboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal; dToronto Western Hospital, University of Toronto, Toronto, Ont., Canada; eUniversity Hospital of Toulouse, Clinical Investigation Center, Departments of Neurosciences and Clinical Pharmacology, INSERM UMR 825, Toulouse, France
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Aims: To investigate the safety and tolerability of pardoprunox (SLV308), a novel partial dopamine agonist, as an adjunct to levodopa in patients with advanced Parkinson’s disease, using two titration schedules. Methods: Patients were randomized to pardoprunox (n = 51) or placebo (n = 11). Pardoprunox was titrated to the highest tolerated dose (range, 0.3–42 mg/day) over 7 weeks, using a gradual dose escalation without intermediate steps (group 1) or with intermediate steps (group 2). Results: The cumulative drop-out rate was greater in group 1 (without intermediate steps, 56.0%) than in group 2 (with intermediate steps, 34.6%), or with placebo (9.1%). In group 2, doses up to 18 mg/day were well tolerated with a cumulative drop-out rate of 7.7% (2/26) and a drop-out rate due to adverse events of 4.0% (1/26). The most common adverse events reported were nausea, vomiting, headache, and dizziness. There was a trend for reduced OFF time (p = 0.054) in the combined pardoprunox group compared to placebo. Conclusions: The pardoprunox safety and tolerability profile as an adjunct to levodopa was improved using a gradual titration schedule that included intermediate dose steps. Using this titration, doses up to 18 mg/day were well tolerated.
© 2009 S. Karger AG, Basel
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