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Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease
Background: CVT-301, an inhaled levodopa (LD) formulation, is under development for relief of OFF periods in Parkinson's disease (PD). Previously, we reported that CVT-301 improved OFF symptoms relative to placebo. In this study, we evaluate pulmonary function in patients treated with a single...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994675/ https://www.ncbi.nlm.nih.gov/pubmed/29161531 http://dx.doi.org/10.1089/jamp.2016.1354 |
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author | LeWitt, Peter A. Pahwa, Rajesh Sedkov, Alexander Corbin, Ann Batycky, Richard Murck, Harald |
author_facet | LeWitt, Peter A. Pahwa, Rajesh Sedkov, Alexander Corbin, Ann Batycky, Richard Murck, Harald |
author_sort | LeWitt, Peter A. |
collection | PubMed |
description | Background: CVT-301, an inhaled levodopa (LD) formulation, is under development for relief of OFF periods in Parkinson's disease (PD). Previously, we reported that CVT-301 improved OFF symptoms relative to placebo. In this study, we evaluate pulmonary function in patients treated with a single dose of CVT-301 or placebo for 3 hours, or received multiple doses/day for 4 weeks. Methods: As part of two phase 2 studies, pulmonary safety and tolerability of CVT-301 were evaluated in PD patients experiencing motor fluctuations (≥2 hours OFF/day), Hoehn and Yahr stage 1–3, and forced expiratory volume in 1 second/forced vital capacity ratio ≥75% of predicted (in ON state). In study A, patients received single doses of oral carbidopa/LD and each of the following via the inhaled route: placebo and 25 and 50 mg LD fine particle dose (FPD) CVT-301. In study B, patients received up to 3 inhaled doses/day of 35 mg (weeks 1–2) and 50 mg LD FPD CVT-301 (weeks 3–4) versus placebo. Assessments included spirometry and treatment-emergent adverse events (TEAEs). Results: In study A, (n = 24) mean age ± standard deviation was 61.3 ± 7.4 years, mean time since diagnosis was 10.5 ± 4.6 years, and mean duration of LD treatment 8.4 ± 3.7 years. Assessment of pulmonary function (predose to 3 hours postdose) showed that spirometry findings were within normal ranges, regardless of treatment groups, or motor status at screening. In study B, (n = 86) mean age was 62.4 ± 8.7 years, time since PD diagnosis was 9.4 ± 3.9 years, and duration of LD treatment 7.8 ± 3.9 years. Longitudinal assessment of pulmonary function over 4 weeks showed no significant difference in spirometry between CVT-301 versus placebo groups. In both studies, the most common CVT-301 TEAE was mild-to-moderate cough (study A: 21%; study B: 7% vs. 2% in placebo). Other common TEAEs in study B were dizziness and nausea. Conclusion: Acute and longitudinal assessment of pulmonary function showed that CVT-301 treatment was not associated with acute airflow obstruction in this population. CVT-301 was generally safe and well tolerated. |
format | Online Article Text |
id | pubmed-5994675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Mary Ann Liebert, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59946752018-06-12 Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease LeWitt, Peter A. Pahwa, Rajesh Sedkov, Alexander Corbin, Ann Batycky, Richard Murck, Harald J Aerosol Med Pulm Drug Deliv Original Research Background: CVT-301, an inhaled levodopa (LD) formulation, is under development for relief of OFF periods in Parkinson's disease (PD). Previously, we reported that CVT-301 improved OFF symptoms relative to placebo. In this study, we evaluate pulmonary function in patients treated with a single dose of CVT-301 or placebo for 3 hours, or received multiple doses/day for 4 weeks. Methods: As part of two phase 2 studies, pulmonary safety and tolerability of CVT-301 were evaluated in PD patients experiencing motor fluctuations (≥2 hours OFF/day), Hoehn and Yahr stage 1–3, and forced expiratory volume in 1 second/forced vital capacity ratio ≥75% of predicted (in ON state). In study A, patients received single doses of oral carbidopa/LD and each of the following via the inhaled route: placebo and 25 and 50 mg LD fine particle dose (FPD) CVT-301. In study B, patients received up to 3 inhaled doses/day of 35 mg (weeks 1–2) and 50 mg LD FPD CVT-301 (weeks 3–4) versus placebo. Assessments included spirometry and treatment-emergent adverse events (TEAEs). Results: In study A, (n = 24) mean age ± standard deviation was 61.3 ± 7.4 years, mean time since diagnosis was 10.5 ± 4.6 years, and mean duration of LD treatment 8.4 ± 3.7 years. Assessment of pulmonary function (predose to 3 hours postdose) showed that spirometry findings were within normal ranges, regardless of treatment groups, or motor status at screening. In study B, (n = 86) mean age was 62.4 ± 8.7 years, time since PD diagnosis was 9.4 ± 3.9 years, and duration of LD treatment 7.8 ± 3.9 years. Longitudinal assessment of pulmonary function over 4 weeks showed no significant difference in spirometry between CVT-301 versus placebo groups. In both studies, the most common CVT-301 TEAE was mild-to-moderate cough (study A: 21%; study B: 7% vs. 2% in placebo). Other common TEAEs in study B were dizziness and nausea. Conclusion: Acute and longitudinal assessment of pulmonary function showed that CVT-301 treatment was not associated with acute airflow obstruction in this population. CVT-301 was generally safe and well tolerated. Mary Ann Liebert, Inc. 2018-06-01 2018-06-01 /pmc/articles/PMC5994675/ /pubmed/29161531 http://dx.doi.org/10.1089/jamp.2016.1354 Text en © Peter A. LeWitt, et al. 2017; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Research LeWitt, Peter A. Pahwa, Rajesh Sedkov, Alexander Corbin, Ann Batycky, Richard Murck, Harald Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease |
title | Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease |
title_full | Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease |
title_fullStr | Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease |
title_full_unstemmed | Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease |
title_short | Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease |
title_sort | pulmonary safety and tolerability of inhaled levodopa (cvt-301) administered to patients with parkinson's disease |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994675/ https://www.ncbi.nlm.nih.gov/pubmed/29161531 http://dx.doi.org/10.1089/jamp.2016.1354 |
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