title: Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials.
abstract: BACKGROUND
  Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours.
  
  
  OBJECTIVE
  To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting.
  
  
  METHODS
  Patients had ≥2.5 hours/day of "off" time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided.
  
  
  RESULTS
  Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily "off" time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE.
  
  
  CONCLUSIONS
  Among PD patients with substantial "off" time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.
authors.affiliation: Wisconsin Institute for Neurologic and Sleep Disorders, Milwaukee, WI, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nausieda
authors.affiliation: Impax Laboratories, Inc., Hayward, CA, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Hsu
authors.affiliation: University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Elmer
authors.affiliation: Charlotte Neurological Services, Port Charlotte, FL, USA.
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Gil
authors.affiliation: Saarland University, Homburg/Saar, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Spiegel
authors.affiliation: University of Miami, Miami, FL, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Singer
authors.affiliation: Impax Laboratories, Inc., Hayward, CA, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Khanna
authors.affiliation: Impax Laboratories, Inc., Hayward, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Rubens
authors.affiliation: Impax Laboratories, Inc., Hayward, CA, USA.
authors.forename: Sherron
authors.initials: S
authors.lastname: Kell
authors.affiliation: Impax Laboratories, Inc., Hayward, CA, USA.
authors.forename: Nishit B
authors.initials: NB
authors.lastname: Modi
authors.affiliation: Impax Laboratories, Inc., Hayward, CA, USA.
authors.forename: Suneel
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002396:Catechols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D004338:Drug Combinations; D009570:Nitriles; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa
keywords: Levodopa; Parkinson’s disease; dyskinesia; extended-release; off-time; on-time