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

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 etilevodopa-carbidopa 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.