Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials
| Autor: | Jordan Dubow, Rejko Krüger, John T. Slevin, Juan Carlos Martínez Castrillo, Janet Benesh, Krai Chatamra, Victor S.C. Fung, Mark F. Lew, Weining Z. Robieson |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Abdominal pain medicine.medical_specialty Internationality Parkinson's disease Levodopa-carbidopa intestinal gel Clinical Neurology Antiparkinson Agents Levodopa Pharmacotherapy Double-Blind Method Humans Medicine Dosing Adverse effect Intubation Gastrointestinal Polypharmacy PEG-J procedure business.industry Carbidopa Motor fluctuations Surgery Clinical trial Drug Combinations Jejunum Intestinal Absorption Dose optimization Neurology Anesthesia Female Neurology (clinical) medicine.symptom Geriatrics and Gerontology business Complication Gels |
| Zdroj: | Parkinsonism & Related Disorders. 21(7):742-748 |
| ISSN: | 1353-8020 |
| DOI: | 10.1016/j.parkreldis.2015.04.022 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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