Inhaled Levodopa (CVT-301) for Treatment of off Periods in Parkinson's Disease: Efficacy as Assessed by 39-Item Parkinson's Disease Quality of Life (QoL) Questionnaire
LeWitt P, Hauser RA, Oh C, Qian J, Kenney C, and Abeynayake I. Inhaled Levodopa (CVT-301) for Treatment of off Periods in Parkinson's Disease: Efficacy as Assessed by 39-Item Parkinson's Disease Quality of Life (QoL) Questionnaire. J Mov Disord 2019; 34:S7-S8.
J Mov Disord
Objective: Pre-specified and post-hoc analyses investigated QoL changes as assessed by the 39-item Parkinson's Disease Questionnaire (PDQ-39) over the 12-week period of a phase 3 study (SPAN-PD) and its correlation with changes in Patient Global Impression of Change (PGIC). Background: Inbrija (CVT-301) is a levodopa inhalation powder developed for the intermittent treatment of OFF episodes in patients on a carbidopa/levodopa regimen. In the SPAN-PDSM study, CVT-301 84mg significantly improved motor function in patients experiencing OFF periods, as measured by lower UPDRS-III scores 30 minutes post-dose, evaluated at 12 weeks. Positive treatment effect was observed in PGIC. Methods: This was a 12-week study of PD patients experiencing motor fluctuations on a standard oral carbidopa/levodopa regimen. Patients were randomized to placebo, CVT-301 60mg or 84mg (1:1:1) for the treatment of OFF period symptoms as needed up to 5 times/day. PDQ-39 and PGIC were completed at baseline, 4, 8, and 12 weeks. A post-hoc analysis using an anchor-based approach examined the change in PDQ-39 domains (mobility and activities of daily living [ADL]). The PGIC (scored from 1["much improved"] to 7["much worse"]) was used as anchor for the 12-week study period. Results: Improvement in PDQ-39 ADL and mobility was linked to the minimum improvement in PGIC ("a little improved") with estimated changes of-1.979(P=0.01) for ADL and-1.335(P=0.06) for mobility scores when the 3 treatment arms were pooled. Estimated treatment differences vs placebo for the CVT-301 84-mg dose were-2.08, for ADL, and-2.19 for mobility. For both doses, treatment differences in ADL and mobility were above the estimates correlating with minimum improvement in PGIC. Conclusions: Patients treated with CVT-301 showed more improvement in ADL and mobility as assessed by PDQ-39 which correlated with improvement in PGIC as compared with placebo-treated patients at 12 weeks. Maintaining independence in ADL helps optimize QoL for PD patients.