TY - JOUR
T1 - Initiation and dose optimization for levodopa-carbidopa intestinal gel
T2 - Insights from phase 3 clinical trials
AU - Lew, Mark F.
AU - Slevin, John T.
AU - Krüger, Rejko
AU - Martínez Castrillo, Juan Carlos
AU - Chatamra, Krai
AU - Dubow, Jordan S.
AU - Robieson, Weining Z.
AU - Benesh, Janet A.
AU - Fung, Victor S.C.
N1 - Funding Information:
Dr. Lew has been a study investigator and a speaker for Teva, USWM, Ipsen, and UCB; an advisor/consultant to Teva, USWM, Ipsen, Schering-Plough, Merz, Abbott, Impax, and Baxter; a researcher for the NIH, Abbott/AbbVie, Schering-Plough, Parkinson's Study Group, USWM, The Michael J. Fox Foundation for Parkinson's Research, Synosia Pharmaceuticals, Merz, and Ipsen; and received foundation grants from the National Parkinson's Disease Foundation, HollyRod Foundation, and Gene and Kathy Monroe Foundation.
Funding Information:
Dr. Krüger has received research grants from the German Research Council, The Michael J. Fox Foundation, Fritz Thyssen Foundation, the Federal Ministry for Education Germany and Research, and the Fonds National de la Recherche Luxembourg; has been a study investigator for Medtronic GmbH and AbbVie Inc.; and has received speaker's honoraria from Medtronic GmbH, St. Jude Medical, and AbbVie Inc..
Publisher Copyright:
© 2015 AbbVie Inc, employer of authors K. Chatamra,W. Robieson, and J. Benesh.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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 1572mg at last visit). In the double-blind trial, 84% received polypharmacy; mean titration took 7.1 days for the LCIG arm (TDD post-titration: 1181mg; n=37). At post-PEG-J week 4, mean "off" time with LCIG was reduced by 3.9h (open-label/monotherapy study) and 3.7h (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.
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 1572mg at last visit). In the double-blind trial, 84% received polypharmacy; mean titration took 7.1 days for the LCIG arm (TDD post-titration: 1181mg; n=37). At post-PEG-J week 4, mean "off" time with LCIG was reduced by 3.9h (open-label/monotherapy study) and 3.7h (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.
KW - Dosing
KW - Levodopa-carbidopa intestinal gel
KW - Motor fluctuations
KW - PEG-J procedure
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84930762500&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2015.04.022
DO - 10.1016/j.parkreldis.2015.04.022
M3 - Article
C2 - 25962554
AN - SCOPUS:84930762500
SN - 1353-8020
VL - 21
SP - 742
EP - 748
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 7
ER -