Early treatment benefits of ropinirole prolonged release in Parkinson's disease patients with motor fluctuations.

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE-PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2-24 mg/day) versus placebo in patients with moderate-to-advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in "off" time (adjusted mean treatment difference [AMTD] - 0.7 hours; 95% confidence interval [CI], -1.1, -0.2; P = 0.0029), and "on" time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, -3.1; 95%CI, -4.4, -1.8; P < 0.0001), activities of daily living score (AMTD, -1.1; 95%CI, -1.7, -0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once-daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation.

Orally disintegrating selegiline in Parkinson patients with dopamine agonist-related adverse effects.

OBJECTIVE: To determine whether adding orally disintegrating selegiline (ODS) while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations, and impulse control disorders (ICDs) without compromising efficacy in Parkinson disease (PD) patients. METHODS: This was a 12-week open-label study of 60 PD patients with motor fluctuations and DA-related AEs of EDS, pedal edema, hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25 mg once daily, and down titration of the DA was started with a goal of a 50% reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further reductions of the DA were allowed if the AEs were not resolved. RESULTS: The addition of ODS allowed a reduction in the mean daily dose of pramipexole from 2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73% with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n = 25). Mean activities of daily living and motor scores from the Unified Parkinson's Disease Rating Scale as well as quality-of-life scores were significantly improved without an increase in daily "off" time. The most common AEs, most of which resolved after titration, were worsening of PD, nausea/vomiting, dyskinesia, increased off time, body aches, insomnia, orthostatic hypotension, and increased anxiety and depression. CONCLUSIONS: In most subjects, the addition of ODS with decreasing dosages of DAs substantially reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.

Ropinirole 24-hour prolonged release and ropinirole immediate release in early Parkinson's disease: a randomized, double-blind, non-inferiority crossover study.

OBJECTIVE: This study compares once-daily ropinirole 24-h prolonged release and three-times-daily ropinirole immediate release in patients with early Parkinson's disease. METHODS: This multicentre, double-blind, non-inferiority crossover study involved 161 patients randomized to one of four formulation sequences: (1) immediate release-immediate release-prolonged release; (2) immediate release-prolonged release-prolonged release; (3) prolonged release-prolonged release-immediate release; (4) prolonged release-immediate release-immediate release. During a 12-week dose-titration period, ropinirole immediate release was titrated according to the approved labelling; titration of ropinirole 24-h prolonged release started at a higher dose and was more rapid. Patients then entered three consecutive, flexible-dose, 8-week maintenance periods. At the end of the first maintenance period, half of the patients in each formulation group switched to the same or closest dose of the alternative formulation; remaining patients switched at the end of the second maintenance period. RESULTS: At the end of titration, before the first dose switch, there were substantial reductions in mean Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. During maintenance periods, both groups showed similar efficacy on the UPDRS motor score. Overall mean (standard error) change from period baseline was -0.1 (0.28) for ropinirole 24-h prolonged release, and 0.6 (0.30) for ropinirole immediate release (adjusted mean treatment difference -0.7; 95% confidence interval [CI]: -1.51, 0.10; p = 0.0842). The upper limit of the 95% CI was less than the predefined threshold of 3 points for non-inferiority. Ropinirole 24-h prolonged release was well-tolerated when titrated more rapidly than ropinirole immediate release; overnight switching between formulations was also well-tolerated. Study limitations included complexity of the non-inferiority study design and the forced dose-titration schedule. CONCLUSION: Ropinirole 24-h prolonged release was effective and well-tolerated in patients with early Parkinson's disease.