Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials

• Published in: Parkinsonism & related disorders Vol. 21; no. 7; pp. 742 - 748
• Main Authors: Lew, Mark F, Slevin, John T, Krüger, Rejko, Martínez Castrillo, Juan Carlos, Chatamra, Krai, Dubow, Jordan S, Robieson, Weining Z, Benesh, Janet A, Fung, Victor S.C
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2015
• Subjects: Antiparkinson Agents - administration & dosage; Antiparkinson Agents - metabolism; Carbidopa - administration & dosage; Carbidopa - metabolism; Dosing; Double-Blind Method; Drug Combinations; Female; Gels; Humans; Internationality; Intestinal Absorption - drug effects; Intubation, Gastrointestinal - methods; Jejunum - drug effects; Jejunum - metabolism; Levodopa - administration & dosage; Levodopa - metabolism; Levodopa-carbidopa intestinal gel; Male; Motor fluctuations; Neurology; Parkinson's disease; PEG-J procedure; Motor fluctuations; Dosing; PEG-J procedure; Levodopa-carbidopa intestinal gel; Parkinson's disease
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2015.04.022

Abstract Background Levodopa-carbidopa intestinal gel (LCIG) provides continuous infusion and reduces “off” time in advanced Parkinson's disease (PD) patients with motor fluctuations despite optimized pharmacotherapy. Methods Clinical experience with 2 LCIG dosing paradigms from phase 3 studies was examined. In an open-label, 54-week study, LCIG was initiated as daytime monotherapy via nasojejunal (NJ) tube then switched to percutaneous endoscopic gastrojejunostomy (PEG-J) tube; adjunctive therapy was permitted 28 days postPEG-J. In a 12-week, double-blind, placebo-controlled, double-dummy trial, patients continued stable doses of existing anti-PD medications, but LCIG replaced daytime oral levodopa-carbidopa and was initiated directly via PEG-J. Results In the open-label study, 92% of 354 patients received monotherapy at post–PEG-J week 4; mean titration duration was 7.6 days; dosing remained stable post-titration (mean total daily dose [TDD] was 1572 mg at last visit). In the double-blind trial, 84% received polypharmacy; mean titration took 7.1 days for the LCIG arm (TDD post-titration: 1181 mg; n  = 37). At post–PEG-J week 4, mean “off” time with LCIG was reduced by 3.9 h (open-label/monotherapy study) and 3.7 h (double-blind/polypharmacy trial). NJ treatment (open-label study only) required an additional procedure with related adverse events (AEs) and withdrawals. The most common AEs during PEG-J weeks 1–4 in the open-label/monotherapy and double-blind/polypharmacy trials, respectively, were complication of device insertion (35%, 57%) and abdominal pain (26%, 51%). Discontinuations due to nonprocedure/nondevice AEs were low (2.2%, 2.7%). Conclusion These results support the option of initiating LCIG with or without NJ and as either monotherapy or polypharmacy.