Improvements in nocturnal symptoms with ropinirole prolonged release in patients with advanced Parkinson's disease

Background: The 24-week, double-blind Efficacy and Safety Evaluation in PD-Adjunct (EASE-PD Adjunct) study randomized patients with advanced Parkinsons disease (PD) suboptimally controlled with levodopa to once-daily placebo or adjunctive ropinirole prolonged release (2-24 mg/day). We investigated the effect of ropinirole prolonged release on nocturnal symptoms in these patients. Methods: Total and grouped item PD Sleep Scale (PDSS) scores were analyzed post hoc in patients with baseline PDSS total scores <= 100 (troublesome nocturnal symptoms) and > 100. Results: Baseline PDSS total score was <= 100 in 93 of 198 (47%) and 89 of 189 (47%) patients receiving ropinirole prolonged release and placebo, respectively; this subgroup displayed evidence at baseline of greater daily awake 'off' time, reduced nighttime sleep and worse quality of life, than the PDSS > 100 subgroup. Significant improvements with ropinirole prolonged release versus placebo in PDSS score from baseline to Week 24 last observation carried forward were observed for those with baseline PDSS mu 100 [ adjusted mean treatment difference 9.0 (95% CI: 2.76, 15.33; P = 0.0051)], but not > 100. The PDSS <= 100 subgroup demonstrated treatment benefits for PDSS groupings of motor symptoms on waking and global quality of sleep. Changes in daytime sleepiness were similar between treatment groups. The PDSS > 100 subgroup demonstrated significant treatment benefit for global quality of sleep. The unadjusted odds ratio for a positive response with ropinirole prolonged release relative to placebo, for the PDSS <= 100 subgroup, was 2.90 (95% CI: 1.42, 5.95, P = 0.004). Conclusions: Once-daily ropinirole prolonged release improves nocturnal symptoms in patients with advanced PD not optimally controlled with levodopa who suffer troublesome nocturnal disturbance.