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

Abstract

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 dyskinesias 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 Parkinson disease and disabling dyskinesias.

Interventions: Randomly received daily doses of 150 mg, 300 mg, or 600 mg of 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 dyskinesia ratings. The MGDRS score correlated with clinic diary ratings of the percentage of "on" time with dyskinesias, and the LFADLDS score correlated with home and clinic diary assessments of percentage of on time with severe dyskinesias. The MGDRS score did not correlate highly with the LFADLDS score. This pilot study also validated previous results demonstrating the safety and tolerability of remacemide treatment for advanced Parkinson disease but did not result in any demonstrable improvement or worsening in dyskinesia measures.

Conclusions: Diaries may provide a valid means of evaluating dyskinesias in clinical trials for Parkinson disease, but there remain other aspects of dyskinesias, as assessed by the MGDRS and LFADLDS, that are not reflected in diary ratings.