title: Long-Term Treatment with Extended-Release Carbidopa-Levodopa (IPX066) in Early and Advanced Parkinson's Disease: A 9-Month Open-Label Extension Trial.
abstract: 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 Cmax (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.
  
  
  CONCLUSIONS
  During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy.
authors.affiliation: Columbia University Medical Center, New York, NY, USA, cw345@columbia.edu.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Waters
authors.forename: Paul
authors.initials: P
authors.lastname: Nausieda
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Dzyak
authors.forename: Joerg
authors.initials: J
authors.lastname: Spiegel
authors.forename: Monika
authors.initials: M
authors.lastname: Rudzinska
authors.forename: Dee E
authors.initials: DE
authors.lastname: Silver
authors.forename: Elena S
authors.initials: ES
authors.lastname: Tsurkalenko
authors.forename: Sherron
authors.initials: S
authors.lastname: Kell
authors.forename: Ann
authors.initials: A
authors.lastname: Hsu
authors.forename: Sarita
authors.initials: S
authors.lastname: Khanna
authors.forename: Suneel
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa