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

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.