Once-Weekly Subcutaneous Delivery of Polymer-Linked Rotigotine (SER-214) Provides Continuous Plasma Levels in Parkinson's Disease Patients.
Parkinson's disease
continuous delivery
polymer-rotigotine
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
25
11
2019
revised:
18
02
2020
accepted:
21
02
2020
pubmed:
7
4
2020
medline:
28
4
2021
entrez:
7
4
2020
Statut:
ppublish
Résumé
Extensive scientific and clinical evidence indicates that continuous delivery of a dopaminergic agent is associated with significant reduction in motor complications compared with intermittent oral dosing with the same agent. There has been an intensive effort to develop a method of providing continuous plasma levels of a dopaminergic agent that avoids the need for surgical therapy or an infusion system. Studies in MPTP-treated monkeys demonstrate that once-weekly injections of polymer-linked rotigotine provide continuous plasma levels and antiparkinsonian benefits. We performed a multicenter open-label, multiple-ascending-dose-ranging cohort study to evaluate the safety, tolerability, and pharmacokinetics of polymer-linked rotigotine in PD patients. A total of 19 patients were evaluated in 4 cohorts in doses of 20 50, 100, and 200 mg of polymer-linked rotigotine, administered subcutaneously once weekly. The study demonstrated remarkably stable dose-related plasma levels of total and free rotigotine with no accumulation or dumping. Treatment was generally safe and well tolerated. One subject in the 50-mg group discontinued because of hives, which cleared rapidly with antihistamine treatment. This study demonstrates that once-a-week subcutaneous administration of polymer-linked rotigotine provides relatively constant plasma levels of rotigotine and is safe and well tolerated. These findings suggest that this convenient method of delivery of rotigotine has the potential to treat or prevent motor complications in PD patients without the need for a surgical procedure or an infusion system. This approach may also prove applicable to other agents such as apomorphine that can be linked to this polymer © 2020 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Extensive scientific and clinical evidence indicates that continuous delivery of a dopaminergic agent is associated with significant reduction in motor complications compared with intermittent oral dosing with the same agent. There has been an intensive effort to develop a method of providing continuous plasma levels of a dopaminergic agent that avoids the need for surgical therapy or an infusion system. Studies in MPTP-treated monkeys demonstrate that once-weekly injections of polymer-linked rotigotine provide continuous plasma levels and antiparkinsonian benefits.
METHODS
We performed a multicenter open-label, multiple-ascending-dose-ranging cohort study to evaluate the safety, tolerability, and pharmacokinetics of polymer-linked rotigotine in PD patients.
RESULTS
A total of 19 patients were evaluated in 4 cohorts in doses of 20 50, 100, and 200 mg of polymer-linked rotigotine, administered subcutaneously once weekly. The study demonstrated remarkably stable dose-related plasma levels of total and free rotigotine with no accumulation or dumping. Treatment was generally safe and well tolerated. One subject in the 50-mg group discontinued because of hives, which cleared rapidly with antihistamine treatment.
CONCLUSIONS
This study demonstrates that once-a-week subcutaneous administration of polymer-linked rotigotine provides relatively constant plasma levels of rotigotine and is safe and well tolerated. These findings suggest that this convenient method of delivery of rotigotine has the potential to treat or prevent motor complications in PD patients without the need for a surgical procedure or an infusion system. This approach may also prove applicable to other agents such as apomorphine that can be linked to this polymer © 2020 International Parkinson and Movement Disorder Society.
Substances chimiques
Dopamine Agonists
0
Polymers
0
Tetrahydronaphthalenes
0
Thiophenes
0
rotigotine
87T4T8BO2E
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1055-1061Informations de copyright
© 2020 International Parkinson and Movement Disorder Society.
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