title: Levodopa-carbidopa intestinal gel in advanced Parkinson's disease open-label study: interim results.
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.
authors.affiliation: Center for Neurological Restoration, Cleveland Clinic, 9500 Euclid Ave, U-2, Cleveland, OH 44195, USA. fernanh@ccf.org
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.forename: Arvydas
authors.initials: A
authors.lastname: Vanagunas
authors.forename: Per
authors.initials: P
authors.lastname: Odin
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Espay
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: David G
authors.initials: DG
authors.lastname: Standaert
authors.forename: Krai
authors.initials: K
authors.lastname: Chatamra
authors.forename: Janet
authors.initials: J
authors.lastname: Benesh
authors.forename: Yili
authors.initials: Y
authors.lastname: Pritchett
authors.forename: Steven L
authors.initials: SL
authors.lastname: Hass
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lenz
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D005260:Female; D005782:Gels / Q000008:administration & dosage; D006801:Humans; D007260:Infusion Pumps; D007583:Jejunum / Q000187:drug effects*; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D005782:Gels; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa