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

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.

Figure 1

Mean change from baseline to final in daily “on” time. Bars are mean (standard deviation) for daily normalized “on” time measures. P values versus baseline are from a 1‐sample t test. A repeated‐measures model with the terms of treatment, country, baseline, and visit and the interaction terms treatment by visit and baseline by visit were used to compare treatment groups in the double‐blind study. LCIG, levodopa‐carbidopa intestinal gel; LC‐IR, immediate release levodopa‐carbidopa.

Figure 2

Mean change from baseline over time in daily “on” time. Data shown are mean daily normalized “on” time measures. P values (1‐sample t test) indicate significance when compared with baseline at ***P ≤ .001,**P ≤ 0.01, and *P ≤ 0.05. LCIG, levodopa‐carbidopa intestinal gel; LC‐IR, immediate release levodopa‐carbidopa; TSD, troublesome dyskinesia; BL, baseline; F, final.

Figure 3

Distribution of time spent in different motor symptoms based on PD diary data. Percentages are of 16 total waking hours. Double‐blind study n = 10 LCIG, 11 LC‐IR; open‐label study n = 139. LCIG, levodopa‐carbidopa intestinal gel; LC‐IR, immediate release levodopa‐carbidopa.