A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations

Abstract

Background: Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration. Objective: To determine the efficacy, safety, and tolerability of etilevodopa in patients with PD who have motor fluctuations. Design: A double-blind, randomized, comparative clinical trial. Setting: Forty-four sites in the United States and Canada. Patients: Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing. Intervention: Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks. Main Outcome Measure: Change from baseline in total daily TTON as measured using home diaries. Results: The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopacarbidopa group and 0.79 hour in the levodopa-carbidopa group (P=.24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P=.20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias. Conclusion: Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa. ©2006 American Medical Association. All rights reserved.