Inhaled drugs offer advantages, such as rapid onset of action, but require 
formulations and delivery systems that reproducibly and conveniently administer 
the drug. CVT-301 is a powder formulation of levodopa delivered by a 
breath-actuated inhaler that has been developed for treating OFF episodes (motor 
fluctuations between doses of standard oral levodopa) in patients with 
Parkinson's disease (PD). We present preclinical, phase 1, and phase 2 results 
for CVT-301. In dogs insufflated with a levodopa powder, plasma levodopa peaked 
in all animals 2.5 min after administration; in contrast, in dogs dosed orally 
with levodopa plus carbidopa, plasma levodopa was not detected until 30 min 
after administration. In 18 healthy persons, comparisons between inhaled CVT-301 
and oral carbidopa/levodopa showed analogous differences in pharmacokinetics. 
Among 24 PD patients inhaling CVT-301 as a single 50-mg dose during an OFF 
episode, 77% showed an increase in plasma levodopa (>400 ng/ml) within 10 min 
versus 27% for oral dosing with carbidopa/levodopa at a 25-mg/100-mg dose. 
Improvements in timed finger tapping and overall motor function (Part III of the 
Unified Parkinson's Disease Rating Scale) were seen 5 and 15 min after 
administration, the earliest assessment time points. For average and best 
change, the improvements were statistically significant compared to placebo. The 
most common adverse event was cough; all cough events were mild to moderate, 
occurred at the time of inhalation, resolved rapidly, and became less frequent 
after initial dosing. These results support further development of CVT-301 for 
better management of PD.