Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson's disease

Robert A Hauser; Stuart H Isaacson; Aaron Ellenbogen; Beth E Safirstein; Daniel D Truong; Steven F Komjathy; Deena M Kegler-Ebo; Ping Zhao; Charles Oh

doi:10.1016/j.parkreldis.2019.03.026

Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson's disease

Parkinsonism Relat Disord. 2019 Jul:64:175-180. doi: 10.1016/j.parkreldis.2019.03.026. Epub 2019 Mar 30.

Authors

Robert A Hauser¹, Stuart H Isaacson², Aaron Ellenbogen³, Beth E Safirstein⁴, Daniel D Truong⁵, Steven F Komjathy⁶, Deena M Kegler-Ebo⁶, Ping Zhao⁶, Charles Oh⁶

Affiliations

¹ University of South Florida, Tampa, FL, USA. Electronic address: rhauser@health.usf.edu.
² Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA.
³ Quest Research Institute, Bingham Farms, MI, USA.
⁴ MD Clinical, Hallandale Beach, FL, USA.
⁵ The Truong Neuroscience Institute, Orange Coast Memorial Medical Center, Fountain Valley, CA, USA; Department of Psychiatry and Neuroscience, University of California Riverside, Riverside, CA, USA.
⁶ Acorda Therapeutics, Inc., Ardsley, NY, USA.

PMID: 30992235
DOI: 10.1016/j.parkreldis.2019.03.026

Abstract

Background: CVT-301 (Inbrija) is a self-administered orally inhaled levodopa approved for the intermittent treatment of OFF episodes in patients with Parkinson's disease (PD) treated with carbidopa/levodopa. Prior studies only evaluated CVT-301 after the first ON of the day.

Objective and methods: The objective of this study was to evaluate the safety and tolerability of CVT-301 for early morning OFF. Using a randomized, double-blind, 2-way crossover design, eligible patients in the morning OFF state (having not received PD medication overnight) received a single dose of CVT-301 84 mg or placebo on 2 dosing days, immediately after their first morning oral carbidopa/levodopa dose. Safety assessments included treatment-emergent adverse events, vital signs, and patient- and examiner-reported dyskinesia. An exploratory efficacy assessment was examiner-rated time-to-ON with carbidopa/levodopa + CVT-301 vs carbidopa/levodopa + placebo.

Results: Of the 36 patients (mean age 62.9 years) who enrolled and completed the study, 9 (25.0%) reported treatment-emergent adverse events following CVT-301 administration; 4 (11.1%) reported treatment-emergent adverse events following placebo. The most common adverse event was cough (4 [11.1%] for CVT-301 vs 1 [2.8%] for placebo), which was typically mild and transient. Incidence of asymptomatic orthostatic hypotension (CVT-301, 6; placebo, 7) and examiner-rated dyskinesia were similar for both (36-39% mild, 3-6% moderate, and 0% severe). Median time-to-ON was 25.0 min following carbidopa/levodopa + CVT-301 and 35.5 min following carbidopa/levodopa + placebo (P = 0.26). At 30 min, more patients had turned ON following carbidopa/levodopa + CVT-301 administration (66.7%), compared with carbidopa/levodopa + placebo (44.5%) (P = 0.040).

Conclusion: Single doses of CVT-301 84 mg administered with oral carbidopa/levodopa for early morning OFF symptoms were well-tolerated, with no notable safety concerns.

Keywords: CVT-301; Carbidopa; Inbrija; Inhalation; Levodopa; OFF periods.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Inhalation
Aged
Antiparkinson Agents / administration & dosage*
Carbidopa / therapeutic use
Cross-Over Studies
Double-Blind Method
Drug Combinations
Female
Humans
Levodopa / administration & dosage*
Levodopa / therapeutic use
Male
Middle Aged
Parkinson Disease / drug therapy*

Substances

Antiparkinson Agents
Drug Combinations
carbidopa, levodopa drug combination
Levodopa
Carbidopa