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CNS Drugs
Published in: CNS Drugs 4/2015

Open Access 01-04-2015 | Original Research Article

Long-Term Treatment with Extended-Release Carbidopa–Levodopa (IPX066) in Early and Advanced Parkinson’s Disease: A 9-Month Open-Label Extension Trial

Authors: Cheryl H. Waters, Paul Nausieda, Lyudmila Dzyak, Joerg Spiegel, Monika Rudzinska, Dee E. Silver, Elena S. Tsurkalenko, Sherron Kell, Ann Hsu, Sarita Khanna, Suneel Gupta

Published in: CNS Drugs | Issue 4/2015

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Abstract

Background and Objective

IPX066 is a multiparticulate extended-release formulation of carbidopa–levodopa, designed to produce prolonged therapeutic levodopa plasma concentrations. This 9-month open-label extension study assessed its long-term safety and clinical utility in early and advanced Parkinson’s disease (PD).

Methods

Participants were enrolled from two phase III IPX066 studies and one open-label phase II study. Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies. Adjustment was allowed throughout the extension. Clinical utility measures included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings.

Results

Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced patients were taking IPX066 three or four times daily (median: 1450 mg/day). Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa–levodopa, the median dosages correspond to ~500 and ~1015 mg/day of IR levodopa in early and advanced PD, respectively. Based on the plasma profiles previously observed in PD patients, the IPX066 regimens in the extension can be estimated to provide a levodopa C max (maximum plasma drug concentration) similar to or lower than that provided by IR regimens during the antecedent trials. UPDRS and PGI findings showed sustained treatment effects throughout the extension.

Conclusion

During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy.
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Metadata
Title
Long-Term Treatment with Extended-Release Carbidopa–Levodopa (IPX066) in Early and Advanced Parkinson’s Disease: A 9-Month Open-Label Extension Trial
Authors
Cheryl H. Waters
Paul Nausieda
Lyudmila Dzyak
Joerg Spiegel
Monika Rudzinska
Dee E. Silver
Elena S. Tsurkalenko
Sherron Kell
Ann Hsu
Sarita Khanna
Suneel Gupta
Publication date
01-04-2015
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 4/2015
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-015-0242-2

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