Evaluation of dyskinesias in a pilot, randomized, placebo-controlled trialof remacemide in advanced Parkinson disease

Context: Long-term levodopa therapy for Parkinson disease commonly results in motor complications including "on-off" fluctuations and dyskinesias, but it is still unclear how best to assess treatment effects on dyskinesias in clinical trials. Objective: To compare several methods of rating levodopa-induced dyskinesia s to evaluate the effect of remacemide hydrochloride treatment in patients with advanced Parkinson disease. Design: Two-week multicenter randomized, double-blind, placebo-controlled, parallel-group study. Setting: Five academic sites of the Parkinson Study Group. Patients: Thirty-nine subjects at least 30 years old with idiopathic Parkin son disease and disabling dyskinesias. Interventions: Randomly received daily doses of 150 mg, 300 mg, or 600 mg o f remacemide hydrochloride or matching placebo for 2 weeks. Main Outcome Measures: The dyskinesia rating scales used were the Modified Goetz Dyskinesia Rating scale (MGDRS), a newly created Lang-Fahn Activities of Daily Living Dyskinesia scale (LFADLDS), and diary dyskinesia ratings. Results: Patient and investigator diaries showed excellent agreement in dys kinesia ratings. The MGDRS score correlated with clinic diary ratings of th e percentage of "on" time with dyskinesias, and the LFADLDS score correlate d with home and clinic diary assessments of percentage of on time with seve re dyskinesias. The MGDRS score did not correlate highly with the LFADLDS s core. This pilot study also validated previous results demonstrating the sa fety and tolerability of remacemide treatment for advanced Parkinson diseas e but did not result in any demonstrable improvement or worsening in dyskin esia measures. Conclusions: Diaries may provide a valid means of evaluating dyskinesias in clinical trials for Parkinson disease, but there remain other aspects of d yskinesias, as assessed by the MGDRS and LFADLDS, that are not reflected in diary ratings.