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.