Inhaled Levodopa Treats Off Periods in Phase III Trial

VANCOUVER—Inhaled levodopa significantly improves motor function during off periods in patients with Parkinson’s disease, according to phase III trial results presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders.

Levodopa inhalation powder, CVT-301, is being developed by Acorda Therapeutics in Ardsley, New York, for intermittent treatment of off periods. The treatment improved motor scores in a phase II study.

Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit, and colleagues conducted the phase III SPAN-PD study, a 12-week, double-blind, multinational trial, to assess the treatment’s efficacy and safety. The investigators randomized 339 patients 1:1:1 to inhaled placebo, CVT-301 (84 mg), or CVT-301 (60 mg) for use up to five times daily as needed.

Peter A. LeWitt, MD

Patients had idiopathic Parkinson’s disease and two or more hours per day of off time, excluding morning off time. Patients were receiving a stable dopa decarboxylase inhibitor and levodopa regimen, and they did not have chronic respiratory disease within the previous five years. Patients’ mean age was 63.3, and 73.5% were male.

The primary end point was change in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III motor score from predose to 30 minutes post dose with CVT-301 (84 mg) or placebo at week 12, when subjects were evaluated during an off period.

At 30 minutes, improvement in motor scores was significantly greater among patients who received CVT-301 (84 mg), compared with patients who received placebo (9.83 vs 5.91).

A greater proportion of patients who received CVT-301 were in an on state (ie, treatment benefited mobility, slowness, and stiffness) at 60 minutes, compared with patients who received placebo (57.7% of patients who received CVT-301 [84 mg], 55.6% of patients who received CVT-301 [60 mg], and 36.1% of patients who received placebo).

Motor improvement occurred as soon as 10 minutes after the 84-mg dose. Furthermore, a greater percentage of patients reported improvement in Patient Global Impression of Change with CVT-301 than with placebo.

Inhaled levodopa was generally well tolerated, and the adverse events and safety profile were consistent with those in a phase IIb study.

Cough was the most common adverse event with CVT-301 versus placebo (15% vs 1.8%). Other adverse events in the 84-mg group included upper respiratory tract infection (6.1%), nausea (5.3%), and sputum discoloration (5.3%).

—Jake Remaly