Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12-month pulmonary safety study

Donald G. Grosset*, Rohit Dhall, Tanya Gurevich, Jan Kassubek, Werner H. Poewe, Olivier Rascol, Monika Rudzinska, Jennifer Cormier, Alexander Sedkov, Charles Oh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Introduction: CVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's disease patients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg). Methods: Patients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care. Pulmonary safety was assessed using spirometry and carbon monoxide diffusion capacity (DLCO). Exploratory efficacy endpoints, assessed only for CVT-301, included change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), patients achieving ON within 60 min and remaining ON at 60 min, Patient Global Impression of Change (PGIC) scale, and total daily OFF time. Results: Of 408 patients randomized, 310 completed the study (204 in CVT-301 and 106 in OC). Mean 12-month changes from baseline for CVT-301 were −0.105 L (FEV1) and −0.378 mL/min/mm Hg (DLCO), and for OC were −0.117 L and −0.722 mL/min/mm Hg, respectively. Between-group comparisons were not statistically significant. For FEV1/FVC the 12-month change was −0.3 and −1.6, respectively, which was a significant between-group difference. However, between-group differences were not significant at 3 and 9 months and all changes from baseline were small (<2.0%). UPDRS-III scores improved from predose to 60 min postdose at all assessments; 80%–85% of patients switched ON within 60 min and remained ON; and >75% reported improvement in PGIC. OFF time decreased by 1.32–1.42 h/day. Conclusion: CVT-301 84 mg induced no clinically significant differences in pulmonary function compared with the OC. Improvements in motor scores, OFF time, and patient-reported outcomes support clinical efficacy for up to 12 months.

Original languageEnglish
Pages (from-to)4-10
Number of pages7
JournalParkinsonism and Related Disorders
Volume71
DOIs
StatePublished - Feb 2020

Funding

FundersFunder number
AbbVie Israel and Neuroderm Ltd.
Desitin
INSERM-DHOS
Israeli Innovation Authority
Merck-Serono
Mundipharma
Prexton Therapeutics
Quintiles
XenoPort
Pfizer
GlaxoSmithKline
Merck
Sanofi
Medtronic
CHDI Foundation
Teva Pharmaceutical Industries
AbbVie
F. Hoffmann-La Roche
Śląski Uniwersytet Medyczny
Boehringer Ingelheim
Seventh Framework ProgrammeH2020
Ucb
Parkinson's Foundation
Acorda Therapeutics
Kyowa Kirin Pharmaceutical Development
European Commission
Agence Nationale de la Recherche
Centre Hospitalier Universitaire de Toulouse
Servier
H. Lundbeck A/S

    Keywords

    • Efficacy
    • Inhaled levodopa
    • Motor fluctuations
    • Off periods
    • Safety

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