Effect of levodopa-carbidopa intestinal gel on dyskinesia in advanced Parkinson's disease patients

Mov Disord. 2016 Apr;31(4):530-7. doi: 10.1002/mds.26528. Epub 2016 Jan 28.

Abstract

Objective: The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia.

Methods: Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by ≥1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n = 11 levodopa-carbidopa intestinal gel, n = 12 oral levodopa-carbidopa; open label: n = 144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed.

Results: Although not significantly different from oral levodopa treatment (P > .05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline = 3.1 [1.7], change from baseline to final = -1.8 [1.8], P = .014), increase in "on" time without troublesome dyskinesia (baseline = 7.4 [2.2], change = 4.4 [3.6], P = .004), and decrease in "off" time (baseline = 5.5 [1.3], change = -2.7 [2.8], P = .015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r = -.073, P = .842; open label: r = -0.001, P = .992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure.

Conclusion: Our exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease.

Keywords: Parkinson's disease; carbidopa-levodopa enteral suspension; dyskinesia; infusion; levodopa-carbidopa intestinal gel; percutaneous endoscopic gastrojejunostomy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Mucosal
  • Aged
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacology
  • Carbidopa / administration & dosage*
  • Carbidopa / adverse effects
  • Carbidopa / pharmacology
  • Double-Blind Method
  • Drug Combinations
  • Dyskinesia, Drug-Induced / prevention & control*
  • Female
  • Gels
  • Humans
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Levodopa / pharmacology
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • Drug Combinations
  • Gels
  • carbidopa, levodopa drug combination
  • Levodopa
  • Carbidopa