Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials

Parkinsonism Relat Disord. 2015 Jul;21(7):742-8. doi: 10.1016/j.parkreldis.2015.04.022. Epub 2015 Apr 28.

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%).

Conclusion: These results support the option of initiating LCIG with or without NJ and as either monotherapy or polypharmacy.

Trial registration: ClinicalTrials.gov NCT00335153 NCT00357994 NCT00660387.

Keywords: Dosing; Levodopa-carbidopa intestinal gel; Motor fluctuations; PEG-J procedure; Parkinson's disease.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / metabolism
  • Carbidopa / administration & dosage*
  • Carbidopa / metabolism
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Gels
  • Humans
  • Internationality
  • Intestinal Absorption / drug effects*
  • Intubation, Gastrointestinal / methods
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Levodopa / administration & dosage*
  • Levodopa / metabolism
  • Male

Substances

  • Antiparkinson Agents
  • Drug Combinations
  • Gels
  • Levodopa
  • Carbidopa

Associated data

  • ClinicalTrials.gov/NCT00335153
  • ClinicalTrials.gov/NCT00357994
  • ClinicalTrials.gov/NCT00660387