Pardoprunox as adjunct therapy to levodopa in patients with Parkinson's disease experiencing motor fluctuations: results of a double-blind, randomized, placebo-controlled, trial

Abstract

Aims: To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson's disease (PD) experiencing motor fluctuations.

Methods: Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale).

Results: Pardoprunox significantly reduced OFF time versus placebo (-1.62 h/day versus -0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid.

Conclusions: Pardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa-treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non-motor symptoms deserves further investigation.

Trial registration: ClinicalTrials.gov NCT00406588.