title: Comparison of IPX066 with carbidopa-levodopa plus entacapone in advanced PD patients.
abstract: BACKGROUND
  IPX066, an investigational extended-release carbidopa-levodopa (CD-LD) preparation, has demonstrated a rapid attainment and prolonged maintenance of therapeutic LD plasma concentrations in advanced Parkinson's disease (PD). This phase-3 crossover study assessed its efficacy and safety vs. CD-LD plus entacapone (CL + E).
  
  
  METHODS
  At baseline, all patients had motor fluctuations despite a stable regimen of CL + E or CD-LD-entacapone combination tablets (CLE). The study included a 6-week conversion from CL + E or CLE to IPX066, followed by two 2-week, double-blind crossover treatment periods in randomized order, one on IPX066 (and placebo CL + E), the other on CL + E (and placebo IPX066), separated by 1-week open-label IPX066 treatment. The primary efficacy measure was mean percent daily "off" time during waking hours (from patient diaries).
  
  
  RESULTS
  Of 91 randomized patients, 84 completed the study. Their median daily LD dosage was 1495 mg from IPX066 and 600 mg from CL + E, corresponding, after correction for bioavailability, to an approximately 22% higher LD exposure on IPX066. Compared with CL + E, IPX066 demonstrated a lower percent "off" time (24.0% vs. 32.5%; p < 0.0001), lower "off" time (3.8 vs. 5.2 h/day; p < 0.0001), and higher "on" time without troublesome dyskinesia (11.4 vs. 10.0 h/day; p < 0.0001). Other endpoints, including patient-reported treatment preference, also favored IPX066 (p < 0.05). During double-blind treatment, 20.2% and 13.6% of patients reported adverse events on IPX066 and CL + E, respectively. The most common were dyskinesia (4 patients), insomnia (3), and confusional state (3) for IPX066, and fall (2) for CL + E.
  
  
  CONCLUSIONS
  In advanced PD, IPX066 showed improved efficacy, compared with CL + E, and appeared to be well tolerated.
authors.affiliation: Institute for Research and Medical Care (IRCCS) San Raffaele, Rome, Italy. Electronic address: fabrizio.stocchi@fastwebnet.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.affiliation: Impax Laboratories, Hayward, CA, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Hsu
authors.affiliation: Impax Laboratories, Hayward, CA, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Khanna
authors.affiliation: Quest Research Institute, Farmington Hills, MI, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ellenbogen
authors.affiliation: Neurozentrum Achim, Niedersachsen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mahler
authors.affiliation: The Parkinson's Institute and Clinical Center, Sunnyvale, CA, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Liang
authors.affiliation: Saarland University, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dillmann
authors.affiliation: Impax Laboratories, Hayward, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Rubens
authors.affiliation: Impax Laboratories, Hayward, CA, USA.
authors.forename: Sherron
authors.initials: S
authors.lastname: Kell
authors.affiliation: Impax Laboratories, Hayward, CA, USA.
authors.forename: Suneel
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002230:Carbidopa / Q000627:therapeutic use*; D002396:Catechols / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D016138:Walking
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D004338:Drug Combinations; D009570:Nitriles; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa
keywords: Entacapone; IPX066; Levodopa; Motor fluctuations; Parkinson's disease; “Off” time