Levodopa‐carbidopa intestinal gel in advanced Parkinson's disease: Final 12‐month, open‐label results

Hubert H Fernandez,Janet A Benesh,Victor S.C Fung,Fabian Klostermann,Coleen M Hall,David G Standaert,Sylvain Chouinard,Jordan Dubow,Oksana Suchowersky,Eduard Z Yakupov,Weining Z Robieson,Alberto J Espay,Malcolm Steiger,Krai Chatamra,Mark F Lew,Per Odin,Robert A Hauser,Anthony E Lang

doi:10.1002/mds.26123

Abstract

Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. l-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces l-dopa-plasma–level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day “off” time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, “on” time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Highlights

Full financial disclosures and author roles may be found in the online version of this article
Ninety-four patients (26.6%) were on L-dopa monotherapy, whereas 259 (73.2%) were receiving 2 Parkinson’s disease (PD) medications in any combination (primarily dopamine agonists [55.4% of all patients], amantadine [29.9%], and catechol-O-methyltransferase (COMT) inhibitors [28.2%]), all of which were discontinued before L-dopa-carbidopa intestinal gel (LCIG) treatment
LCIG was initiated as monotherapy, replacing both oral L-dopa and other adjunctive PD medications in patients with PD who experienced severe motor complications despite optimized pharmacological therapy

Summary

Patients and Methods

The safety and efficacy of LCIG were evaluated in patients with advanced PD experiencing motor fluctuations despite optimized medical therapy in an openlabel, phase III, 12-month study (ClinicalTrials.gov: NCT00335153). The study methodology has been reported on[22] and is summarized below. The study protocol was approved by the institutional review board/ethics committee at all 86 centers in 16 countries.

Study Design

Results

Discussion