PMID- 25962554 OWN - NLM STAT- MEDLINE DCOM- 20160418 LR - 20210402 IS - 1873-5126 (Electronic) IS - 1353-8020 (Linking) VI - 21 IP - 7 DP - 2015 Jul TI - Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials. PG - 742-8 LID - S1353-8020(15)00175-3 [pii] LID - 10.1016/j.parkreldis.2015.04.022 [doi] AB - 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. CI - Copyright (c) 2015 AbbVie Inc, employer of authors K. Chatamra,W. Robieson, and J. Benesh. Published by Elsevier Ltd.. All rights reserved. FAU - Lew, Mark F AU - Lew MF AD - Department of Neurology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA. Electronic address: Mark.Lew@med.usc.edu. FAU - Slevin, John T AU - Slevin JT AD - Department of Neurology, University of Kentucky, Lexington, KY, USA. FAU - Kruger, Rejko AU - Kruger R AD - Department for Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany; Clinical and Experimental Neuroscience, Luxembourg Center for Systems Biomedicine, University of Luxembourg, Centre Hospitalier Luxembourg, Luxembourg. FAU - Martinez Castrillo, Juan Carlos AU - Martinez Castrillo JC AD - Servicio de Neurologia, IRYCIS, Hospital Ramon y Cajal de Madrid, Madrid, Spain. FAU - Chatamra, Krai AU - Chatamra K AD - AbbVie Inc., North Chicago, IL, USA. FAU - Dubow, Jordan S AU - Dubow JS AD - Formerly with AbbVie Inc., North Chicago, IL, USA. FAU - Robieson, Weining Z AU - Robieson WZ AD - AbbVie Inc., North Chicago, IL, USA. FAU - Benesh, Janet A AU - Benesh JA AD - AbbVie Inc., North Chicago, IL, USA. FAU - Fung, Victor S C AU - Fung VS AD - Department of Neurology, Westmead Hospital and Sydney Medical School, Sydney, Australia. LA - eng SI - ClinicalTrials.gov/NCT00335153 SI - ClinicalTrials.gov/NCT00357994 SI - ClinicalTrials.gov/NCT00660387 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150428 PL - England TA - Parkinsonism Relat Disord JT - Parkinsonism & related disorders JID - 9513583 RN - 0 (Antiparkinson Agents) RN - 0 (Drug Combinations) RN - 0 (Gels) RN - 46627O600J (Levodopa) RN - MNX7R8C5VO (Carbidopa) SB - IM MH - Antiparkinson Agents/*administration & dosage/metabolism MH - Carbidopa/*administration & dosage/metabolism MH - Double-Blind Method MH - Drug Combinations MH - Female MH - Gels MH - Humans MH - Internationality MH - Intestinal Absorption/*drug effects MH - Intubation, Gastrointestinal/methods MH - Jejunum/drug effects/metabolism MH - Levodopa/*administration & dosage/metabolism MH - Male OTO - NOTNLM OT - Dosing OT - Levodopa-carbidopa intestinal gel OT - Motor fluctuations OT - PEG-J procedure OT - Parkinson's disease EDAT- 2015/05/13 06:00 MHDA- 2016/04/19 06:00 CRDT- 2015/05/13 06:00 PHST- 2014/12/19 00:00 [received] PHST- 2015/03/30 00:00 [revised] PHST- 2015/04/26 00:00 [accepted] PHST- 2015/05/13 06:00 [entrez] PHST- 2015/05/13 06:00 [pubmed] PHST- 2016/04/19 06:00 [medline] AID - S1353-8020(15)00175-3 [pii] AID - 10.1016/j.parkreldis.2015.04.022 [doi] PST - ppublish SO - Parkinsonism Relat Disord. 2015 Jul;21(7):742-8. doi: 10.1016/j.parkreldis.2015.04.022. Epub 2015 Apr 28.