Mark F Lew1, John T Slevin2, Rejko Krüger3, Juan Carlos Martínez Castrillo4, Krai Chatamra5, Jordan S Dubow6, Weining Z Robieson5, Janet A Benesh5, Victor S C Fung7. 1. Department of Neurology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA. Electronic address: Mark.Lew@med.usc.edu. 2. Department of Neurology, University of Kentucky, Lexington, KY, USA. 3. Department for Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Clinical and Experimental Neuroscience, Luxembourg Center for Systems Biomedicine, University of Luxembourg, Centre Hospitalier Luxembourg, Luxembourg. 4. Servicio de Neurología, IRYCIS, Hospital Ramón y Cajal de Madrid, Madrid, Spain. 5. AbbVie Inc., North Chicago, IL, USA. 6. Formerly with AbbVie Inc., North Chicago, IL, USA. 7. Department of Neurology, Westmead Hospital and Sydney Medical School, Sydney, Australia.
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.
RCT Entities:
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.
Authors: Melissa Deanna Shepard; Kate Perepezko; Martijn P G Broen; Jared Thomas Hinkle; Ankur Butala; Kelly A Mills; Julie Nanavati; Nicole Mercado Fischer; Paul Nestadt; Gregory Pontone Journal: J Neurol Neurosurg Psychiatry Date: 2019-01-19 Impact factor: 10.154
Authors: Stephen W Pedersen; Martin Suedmeyer; Louis W C Liu; Dirk Domagk; Alison Forbes; Lars Bergmann; Koray Onuk; Ashley Yegin; Teus van Laar Journal: J Multidiscip Healthc Date: 2017-01-04
Authors: David G Standaert; Ramon L Rodriguez; John T Slevin; Michael Lobatz; Susan Eaton; Krai Chatamra; Maurizio F Facheris; Coleen Hall; Kavita Sail; Yash J Jalundhwala; Janet Benesh Journal: Mov Disord Clin Pract Date: 2017-09-20