PEG-J Administration of Therapeutic Agents for Neurological Disorders: Levodopa-Carbidopa Intestinal Gel for Advanced Parkinsonʼs Disease

Abstract

Purpose: To determine whether PEG-J administration of levodopa-carbidopa intestinal gel (LCIG) is an effective method for the treatment of advanced Parkinson's disease (PD). Methods: Levodopa is the most effective treatment for PD. With advanced disease, irregular gastric emptying impedes standard oral levodopa effectiveness leading to “On”/”Off” motor fluctuations and dyskinesias. Two phase 3 clinical studies enrolled advanced PD patients with persistent motor fluctuations despite optimized oral therapy. For this novel treatment, involving the collaboration of neurologists and gastroenterologists, all patients underwent a PEG-J procedure for infusion of LCIG (or placebo gel) directly to the proximal jejunum. A 12-week, randomized, double-blind, double-dummy trial compared the effectiveness of LCIG with standard oral levodopa (LC-oral) at reducing motor fluctuations and improving quality of life. A 54-week open-label international trial examined the long-term safety and efficacy of LCIG. “Off” time (when medication is no longer effective and motor symptoms return), the Unified Parkinson's Disease Rating Scale (UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39) were examined. Adverse events (AEs) were recorded. Results: 71 patients were enrolled in the double-blind, double-dummy trial (n=37 LCIG, 34 LC-Oral), with a mean PD duration of 10.9 years. The reduction in “off” time (P<0.01), improvement in UPDRS Part II (activities of daily living) score (P<0.01) and improvement in PDQ-39 Summary Index (P<0.05) was greater in the LCIG group than in the LC-oral group. Three hundred fifty four patients were enrolled in the long-term, open-label study. As with the double-blind trial, “off” time, UPDRS Part II score and PDQ-39 Summary Index versus baseline were improved at all visits (through Week 54; P<0.01). Most patients (97% in double-blind, 91% in open-label) experienced at least 1 AE; serious AEs occurred in 17% (double-blind) and 31% (open-label). AEs led to discontinuation in 4.2% (double-blind) and 7.6% (open-label). Most AEs were known AEs associated with either levodopa, underlying PD or the procedure and the device. Conclusion: Intrajejunal infusion of LCIG via PEG-J is a novel approach for the long-term delivery of medication in gel form, which improved motor fluctuations and the quality of life in advanced PD patients with limited treatment options. The range of PEG-J complications was within standard ranges reported in the literature and was not increased in this ambulatory patient cohort. Disclosure - Michael Epstein: Dr. Epstein served on the data adjudication panel for this study and has received compensation from AbbVie for serving as a consultant. Dr. Epstein also serves as a lecturer for AbbVie. David Johnson: Dr. Johnson served on the data adjudication panel for this study and has received compensation from AbbVie for serving as a consultant. Robert Hawes: Dr. Hawes served on the data adjudication panel for this study and has received compensation from AbbVie for serving as a consultant. Nathan Schmulewitz: Dr. Schmulewitz serves as a medical advisor and speaker for AbbVie. Arvydas Vanagunas: Dr. Vanagunas has received compensation from AbbVie and CVS Caremark's Pharmacy & Therapeutics Committee for serving as a consultant and has been a scientific advisory board member for AbbVie. Cindy Zadikoff: CZ was a study investigator and has received compensation from AbbVie for serving as a consultant and participating in scientific advisory boards. Rod Gossen: served as executive secretary for this study and is employed by a consulting agency under contract with AbbVie. Susan Eaton, Krai Chatamra, Weining Robieson, Jordan Dubow and Janet Benesh are employees of AbbVie and hold AbbVie stock and/or stock options. AbbVie participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. Michelle M. Koutsantonis, of AbbVie, provided medical writing assistance in the development of this publication. This research was supported by an industry grant from AbbVie.