TY - JOUR
T1 - Long-term treatment with extended-release carbidopa-levodopa (IPX066) in early and advanced Parkinson's disease
T2 - A 9-month open-label extension trial
AU - Waters, Cheryl H.
AU - Nausieda, Paul
AU - Dzyak, Lyudmila
AU - Spiegel, Joerg
AU - Rudzinska, Monika
AU - Silver, Dee E.
AU - Tsurkalenko, Elena S.
AU - Kell, Sherron
AU - Hsu, Ann
AU - Khanna, Sarita
AU - Gupta, Suneel
N1 - Publisher Copyright:
© 2015 The Author(s).
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84937763232&partnerID=8YFLogxK
U2 - 10.1007/s40263-015-0242-2
DO - 10.1007/s40263-015-0242-2
M3 - Article
C2 - 25895021
AN - SCOPUS:84937763232
SN - 1172-7047
VL - 29
SP - 341
EP - 350
JO - CNS Drugs
JF - CNS Drugs
IS - 4
ER -