Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double-blind trials

Authors


  • Relevant conflicts of interest/financial disclosures: Cristina Sampaio is the chairperson of the permanent Steering Committee on the clinical development of pardoprunox and does not have any relevant personal financial interest to disclose. The research department to which Cristina Sampaio is affiliated has received research grants or fees from Astellas, Brane, Eisai, Fujisawa, Grünenthal, Kyowa, Lundbeck, Neurobiotech, Newron, Novartis, Schering-Plough, Serono, Servier, Solvay, UCB, and Xytis. Juliana Bronzova, Serge V. van de Witte, and Ad Theeuwes are employees of Solvay Pharmaceuticals (Solvay is now Abbott). Robert A. Hauser has received honoraria or consulting fees from Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Centopharm, Eisai Ltd., Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Novartis, Ortho McNeil, Pfizer, Prestwick, Schwarz Pharma, Schering, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, Valeant, and Vernalis. Anthony E. Lang has received honoraria or consulting fees from Boehringer Ingelheim, Ceregene, Eisai, GlaxoSmithKline, Medtronic, Novartis, Prestwick, Solvay (member of the pardoprunox Development Steering Committee), Teva, and Valeant. Olivier Rascol has received scientific grants or consulting fees from Boehringer Ingelheim, Eisai Ltd., GlaxoSmithKline, Lundbeck, Novartis, Schering-Plough, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, and UCB. Full financial disclosures and author roles may be found in the online version of this article.

Abstract

This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible-dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least-square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible-dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible-dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible-dose 12–42 mg/day showed the highest dropout rate due to treatment-emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment-emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment-emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society

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