title: Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials.
abstract: BACKGROUND
  Levodopa-carbidopa intestinal gel (LCIG) provides continuous infusion and reduces "off" time in advanced Parkinson's disease (PD) patients with motor fluctuations despite optimized pharmacotherapy.
  
  
  METHODS
  Clinical experience with 2 LCIG dosing paradigms from phase 3 studies was examined. In an open-label, 54-week study, LCIG was initiated as daytime monotherapy via nasojejunal (NJ) tube then switched to percutaneous endoscopic gastrojejunostomy (PEG-J) tube; adjunctive therapy was permitted 28 days postPEG-J. In a 12-week, double-blind, placebo-controlled, double-dummy trial, patients continued stable doses of existing anti-PD medications, but LCIG replaced daytime oral levodopa-carbidopa and was initiated directly via PEG-J.
  
  
  RESULTS
  In the open-label study, 92% of 354 patients received monotherapy at post-PEG-J week 4; mean titration duration was 7.6 days; dosing remained stable post-titration (mean total daily dose [TDD] was 1572 mg at last visit). In the double-blind trial, 84% received polypharmacy; mean titration took 7.1 days for the LCIG arm (TDD post-titration: 1181 mg; n = 37). At post-PEG-J week 4, mean "off" time with LCIG was reduced by 3.9 h (open-label/monotherapy study) and 3.7 h (double-blind/polypharmacy trial). NJ treatment (open-label study only) required an additional procedure with related adverse events (AEs) and withdrawals. The most common AEs during PEG-J weeks 1-4 in the open-label/monotherapy and double-blind/polypharmacy trials, respectively, were complication of device insertion (35%, 57%) and abdominal pain (26%, 51%). Discontinuations due to nonprocedure/nondevice AEs were low (2.2%, 2.7%).
  
  
  CONCLUSIONS
  These results support the option of initiating LCIG with or without NJ and as either monotherapy or polypharmacy.
authors.affiliation: Department of Neurology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA. Electronic address: Mark.Lew@med.usc.edu.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lew
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Slevin
authors.affiliation: Department for Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Clinical and Experimental Neuroscience, Luxembourg Center for Systems Biomedicine, University of Luxembourg, Centre Hospitalier Luxembourg, Luxembourg.
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
authors.affiliation: Servicio de Neurología, IRYCIS, Hospital Ramón y Cajal de Madrid, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martínez Castrillo
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Krai
authors.initials: K
authors.lastname: Chatamra
authors.affiliation: Formerly with AbbVie Inc., North Chicago, IL, USA.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Dubow
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Benesh
authors.affiliation: Department of Neurology, Westmead Hospital and Sydney Medical School, Sydney, Australia.
authors.forename: Victor S C
authors.initials: VS
authors.lastname: Fung
mesh_terms: D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000378:metabolism; D002230:Carbidopa / Q000008:administration & dosage* / Q000378:metabolism; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005782:Gels; D006801:Humans; D038622:Internationality; D007408:Intestinal Absorption / Q000187:drug effects*; D007441:Intubation, Gastrointestinal / Q000379:methods; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D005782:Gels; D007980:Levodopa; D002230:Carbidopa
keywords: Dosing; Levodopa-carbidopa intestinal gel; Motor fluctuations; PEG-J procedure; Parkinson's disease