Levodopa–carbidopa intestinal gel in advanced Parkinson's disease open-label study: Interim results

• Published in: Parkinsonism & related disorders 2013-03, Vol.19 (3), p.339-345
• Main Authors: Fernandez, Hubert H, Vanagunas, Arvydas, Odin, Per, Espay, Alberto J, Hauser, Robert A, Standaert, David G, Chatamra, Krai, Benesh, Janet, Pritchett, Yili, Hass, Steven L, Lenz, Robert A
• Format: Article
• Language: English
• Subjects: Aged; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - adverse effects; Basal ganglia; Carbidopa - administration & dosage; Carbidopa - adverse effects; Drug Combinations; Female; Gels - administration & dosage; Humans; Infusion Pumps; Jejunum - drug effects; Levodopa - administration & dosage; Levodopa - adverse effects; Levodopa–carbidopa intestinal gel; Male; Middle Aged; Motor fluctuations; Neurology; Parkinson Disease - drug therapy; Parkinson's disease; PEG-J procedure; Pump administration
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2012.11.020

Abstract Levodopa–carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson's disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients ( n  = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson's Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean “Off” time was 6.7 h/day. “Off” time was reduced by a mean of 3.9 (±3.2) h/day and “On” time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common.