title: A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Henry Ford Hospital and Wayne State University School of Medicine, West Bloomfield, Michigan, USA. plewitt1@hfhs.org.
authors.forename: Peter A
authors.initials: PA
authors.lastname: LeWitt
authors.affiliation: University of South Florida Byrd Parkinson Disease and Movement Disorders Center, Tampa, Florida, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.affiliation: Institute of Neurological Sciences, Glasgow, United Kingdom.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Grosset
authors.affiliation: IRCCS San Raffaele, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Saint-Hilaire
authors.affiliation: Quest Research Institute and Michigan Institute for Neurological Disorders, Farmington Hills, Michigan, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ellenbogen
authors.affiliation: 4Pharma AB, Stockholm, Sweden.
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.affiliation: Virginia Mason Medical Center, Seattle, Washington, USA.
authors.forename: Neil B
authors.initials: NB
authors.lastname: Hampson
authors.affiliation: Acorda Therapeutics, Chelsea, Massachusetts, USA.
authors.forename: Tia
authors.initials: T
authors.lastname: DeFeo-Fraulini
authors.affiliation: Acorda Therapeutics, Chelsea, Massachusetts, USA.
authors.forename: Martin I
authors.initials: MI
authors.lastname: Freed
authors.affiliation: Clintrex LLC, Rye, New York, USA.
authors.forename: Karl D
authors.initials: KD
authors.lastname: Kieburtz
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D015259:Dopamine Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D015259:Dopamine Agents; D007980:Levodopa
keywords: CVT-301; Parkinson's disease; clinical trial; levodopa; motor fluctuations