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

Grosset, D. G. , Dhall, R., Gurevich, T., Kassubek, J., Poewe, W. H., Rascol, O., Rudzinska, M., Cormier, J., Sedkov, A. and Oh, C. (2020) Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12-month pulmonary safety study. Parkinsonism and Related Disorders, 71, pp. 4-10. (doi: 10.1016/j.parkreldis.2019.12.012) (PMID:31927343)

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.

• Item Type: Articles
• Keywords: Efficacy, inhaled levodopa, motor fluctuations, off periods, safety.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Grosset, Professor Donald
• Authors: Grosset, D. G., Dhall, R., Gurevich, T., Kassubek, J., Poewe, W. H., Rascol, O., Rudzinska, M., Cormier, J., Sedkov, A., and Oh, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Parkinsonism and Related Disorders
• Publisher: Elsevier
• ISSN: 1353-8020
• ISSN (Online): 1873-5126
• Published Online: 23 December 2019
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Parkinsonism and Related Disorders 71:4-10
• Publisher Policy: Reproduced under a Creative Commons licence