BACKGROUND: Although levodopa is the most effective oral PD therapy, many 
patients experience motor fluctuations, including sudden loss of dose effect and 
delayed benefit. CVT-301 is a levodopa inhalation powder with the potential for 
rapid onset of action. The objective of this study was to evaluate CVT-301 
self-administered by PD patients to relieve OFF episodes.
METHODS: PD patients with ≥2 hours per day of OFF time despite oral levodopa ≥4 
times per day were randomized to CVT-301 or placebo for 4 weeks, to be used up 
to 3 times per day for OFF episodes. After 2 weeks, the study-drug dose was 
escalated from 35 to 50 mg. The primary end point was mean change in UPDRS Part 
III score from a predose OFF state to the average of postdose scores obtained at 
10, 20, 30, and 60 minutes, as assessed in-clinic at the end of week 4. Home 
diaries were recorded.
RESULTS: Eighty-six patients used the study drug at an average frequency of 2.1 
times per day for CVT-301 and for placebo. At 4 weeks, least-squares mean change 
in UPDRS Part III score favored CVT-301 by 7.0 points (P < 0.001). A treatment 
effect was evident at 10 minutes. At 4 weeks, least-squares mean OFF-time change 
from baseline favored CVT-301 by 0.9 hours per day (P = 0.045). The most 
frequently reported adverse events in the CVT-301 group were dizziness, cough, 
and nausea, each in 7% (3 of 43 patients).
CONCLUSIONS: CVT-301 self-administered during OFF episodes provided rapid 
improvement of motor function, and daily OFF time was significantly reduced at 
the higher dose. CVT-301 was generally safe and well-tolerated. © 2016 The 
Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of 
International Parkinson and Movement Disorder Society.