Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results.

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.

• Authors: Hubert H Fernandez, David G Standaert, Robert A Hauser, Anthony E Lang, Victor S C Fung, Fabian Klostermann, Mark F Lew, Per Odin, Malcolm Steiger, Eduard Z Yakupov, Sylvain Chouinard, Oksana Suchowersky, Jordan Dubow, Coleen M Hall, Krai Chatamra, Weining Z Robieson, Janet A Benesh, Alberto J Espay
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 30 Issue 4 Pg. 500-9 (Apr 2015) ISSN: 1531-8257 [Electronic] United States
• PMID: 25545465 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Chemical References

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

Topics

• Adult
• Aged
• Antiparkinson Agents (therapeutic use)
• Carbidopa (therapeutic use)
• Drug Combinations
• Female
• Gels (therapeutic use)
• Humans
• Intestines (drug effects, physiology)
• Levodopa (therapeutic use)
• Male
• Middle Aged
• Parkinson Disease (drug therapy)
• Prospective Studies
• Severity of Illness Index
• Treatment Outcome