title: Pardoprunox in early Parkinson's disease: results from 2 large, randomized double-blind trials.
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.
authors.affiliation: Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Lisboa, Portugal. crissampaio@mail.telepac.pt
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: Juliana
authors.initials: J
authors.lastname: Bronzova
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Serge V
authors.initials: SV
authors.lastname: van de Witte
authors.forename: And Ad
authors.initials: AA
authors.lastname: Theeuwes
mesh_terms: D000368:Aged; D000977:Antiparasitic Agents / Q000627:therapeutic use*; D001583:Benzoxazoles / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000977:Antiparasitic Agents; D001583:Benzoxazoles; D010879:Piperazines; C480679:pardoprunox