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Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules
OBJECTIVE: IPX203 is an investigational oral extended-release capsule formulation of carbidopa-levodopa (CD-LD). The aim of this study was to characterize the single-dose pharmacodynamics, pharmacokinetics, and safety of IPX203 in subjects with advanced Parkinson disease compared with immediate-rele...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654938/ https://www.ncbi.nlm.nih.gov/pubmed/30520758 http://dx.doi.org/10.1097/WNF.0000000000000314 |
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author | Modi, Nishit B. Mittur, Aravind Rubens, Robert Khanna, Sarita Gupta, Suneel |
author_facet | Modi, Nishit B. Mittur, Aravind Rubens, Robert Khanna, Sarita Gupta, Suneel |
author_sort | Modi, Nishit B. |
collection | PubMed |
description | OBJECTIVE: IPX203 is an investigational oral extended-release capsule formulation of carbidopa-levodopa (CD-LD). The aim of this study was to characterize the single-dose pharmacodynamics, pharmacokinetics, and safety of IPX203 in subjects with advanced Parkinson disease compared with immediate-release (IR) CD-LD and extended-release CD-LD (Rytary). METHODS: This was a randomized, open-label, rater-blinded, multicenter, single-dose crossover study. Blinded clinicians assessed subject's motor state and Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores for up to 10 hours postdose. Duration of effect was determined using improvement thresholds in the MDS-UPDRS part III. RESULTS: Levodopa concentrations increased rapidly and similarly across all 3 treatments and were sustained for a longer duration after IPX203 dosing. All treatments exhibited a rapid onset of pharmacodynamic effect, whereas IPX203 had a significantly longer duration of effect based on MDS-UPDRS part III scores compared with IR CD-LD (P < 0.0001) and Rytary (P ≤ 0.0290). IPX203 had a 2.7-hour advantage over IR CD-LD (P < 0.0001) and a 0.9-hour advantage over Rytary in “off” time (P = 0.023) and in “good on” time (2.6 hours more than IR CD-LD, P < 0.0001; 0.9 hours more than Rytary, P = 0.0259) as measured by the Investigator Assessment of Subject's Motor State. Subjects were 77% more likely to require rescue following IR CD-LD treatment compared with IPX203 (hazard ratio, 0.23; P < 0.0001). More subjects reported treatment-emergent adverse effects during IR CD-LD (28.0%) and IPX203 (19.2%) than during Rytary (8.0%) treatment. CONCLUSIONS: Compared with Rytary and IR CD-LD, IPX203 had a longer pharmacodynamic effect consistent with LD pharmacokinetics for the 3 treatments. The safety and tolerability of IPX203 were similar to those of IR CD-LD and Rytary. |
format | Online Article Text |
id | pubmed-7654938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-76549382020-11-16 Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules Modi, Nishit B. Mittur, Aravind Rubens, Robert Khanna, Sarita Gupta, Suneel Clin Neuropharmacol Original Articles OBJECTIVE: IPX203 is an investigational oral extended-release capsule formulation of carbidopa-levodopa (CD-LD). The aim of this study was to characterize the single-dose pharmacodynamics, pharmacokinetics, and safety of IPX203 in subjects with advanced Parkinson disease compared with immediate-release (IR) CD-LD and extended-release CD-LD (Rytary). METHODS: This was a randomized, open-label, rater-blinded, multicenter, single-dose crossover study. Blinded clinicians assessed subject's motor state and Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores for up to 10 hours postdose. Duration of effect was determined using improvement thresholds in the MDS-UPDRS part III. RESULTS: Levodopa concentrations increased rapidly and similarly across all 3 treatments and were sustained for a longer duration after IPX203 dosing. All treatments exhibited a rapid onset of pharmacodynamic effect, whereas IPX203 had a significantly longer duration of effect based on MDS-UPDRS part III scores compared with IR CD-LD (P < 0.0001) and Rytary (P ≤ 0.0290). IPX203 had a 2.7-hour advantage over IR CD-LD (P < 0.0001) and a 0.9-hour advantage over Rytary in “off” time (P = 0.023) and in “good on” time (2.6 hours more than IR CD-LD, P < 0.0001; 0.9 hours more than Rytary, P = 0.0259) as measured by the Investigator Assessment of Subject's Motor State. Subjects were 77% more likely to require rescue following IR CD-LD treatment compared with IPX203 (hazard ratio, 0.23; P < 0.0001). More subjects reported treatment-emergent adverse effects during IR CD-LD (28.0%) and IPX203 (19.2%) than during Rytary (8.0%) treatment. CONCLUSIONS: Compared with Rytary and IR CD-LD, IPX203 had a longer pharmacodynamic effect consistent with LD pharmacokinetics for the 3 treatments. The safety and tolerability of IPX203 were similar to those of IR CD-LD and Rytary. Lippincott Williams & Wilkins 2019 2018-12-21 /pmc/articles/PMC7654938/ /pubmed/30520758 http://dx.doi.org/10.1097/WNF.0000000000000314 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Original Articles Modi, Nishit B. Mittur, Aravind Rubens, Robert Khanna, Sarita Gupta, Suneel Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules |
title | Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules |
title_full | Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules |
title_fullStr | Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules |
title_full_unstemmed | Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules |
title_short | Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules |
title_sort | single-dose pharmacokinetics and pharmacodynamics of ipx203 in patients with advanced parkinson disease: a comparison with immediate-release carbidopa-levodopa and with extended-release carbidopa-levodopa capsules |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654938/ https://www.ncbi.nlm.nih.gov/pubmed/30520758 http://dx.doi.org/10.1097/WNF.0000000000000314 |
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