Inhaled levodopa (CVT-301 84mg) significantly improves motor function during off periods in Parkinson's disease (PD) subjects: A phase 3 study (SPAN-PD™)
LeWitt PA, Fernandez HH, Hauser RA, Isaacson SH, Lew M, Pahwa R, Saint-Hilaire M, Waters C, Sedkov A, and Oh C. Inhaled levodopa (CVT-301 84mg) significantly improves motor function during off periods in Parkinson's disease (PD) subjects: A phase 3 study (SPAN-PD™). Mov Disord 2017; 32(9):e1-e2.
Objective: To evaluate efficacy and safety of CVT-301 vs placebo in PD subjects during OFF periods. Background: CVT-301, an investigational, inhaled therapy that delivers levodopa to the lungs, is intended to treat OFF periods for patients on a dopa-decarboxylase inhibitor/levodopa regimen. Methods: A 12-week, double-blind, placebo-controlled study of PD subjects experiencing motor fluctuations. Subjects were randomized to placebo, CVT-301 84mg or 60mg (1:1:1). Treatment was up to 5 times daily. Efficacy analyses were performed using a prespecified hierarchical testing. Primary efficacy endpoint: change in UPDRS part III score at 30min from pre-to postdose with CVT-301 84mg vs placebo at week 12 evaluated during an OFF period. Key secondary endpoints: ON responders within 60min; change in UPDRS part III score at 20min postdose; improvement in PGIC; change in UPDRS part III score at 10min postdose; and total daily OFF time. Safety profile, including pulmonary function, was assessed. Nominal P-values are presented for key secondary endpoints that were not statistically significant due to the hierarchy. Results: 339 randomized subjects received at least 1 dose of CVT-301 or placebo; 290 completed the study (mean age 63.3years, mean PD duration 8.3years, mean total OFF time 5.5hours). Primary endpoint was 29.8 for 84mg vs 25.9 for placebo (P50.009). At week-12, 58% on 84mg vs 36% on placebo were ON responders within 60min (P<0.05), and 71% on 84mg vs 46% on placebo reported improvement in PGIC (nominal P<0.05). 84mg vs placebo improved in UPDRS part III at 10min, which was sustained for 1hour. Most common AE for 84mg vs placebo was cough (14.9% vs 1.8%). Spirometry data showed no significant pulmonary safety indicators. Conclusion: Findings confirmed that compared with placebo, CVT-301 84mg showed a clinically meaningful response in the treatment of OFF periods, based on the Shulman criteria. CVT-301 was generally well tolerated.