Long‐term safety and efficacy of levodopa‐carbidopa intestinal gel in advanced Parkinson's disease

Abstract

A BST RACT : Background: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program. Methods: PD patients (n 5 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673). Safety and efficacy assessments were collected every 6 months. Results: Mean total duration of exposure to levodopacarbidopa intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall discontinuation rate was 34% (average annual discontinuation rate, 10%). Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event. Of patients in this extension study, 54% required jejunal tube replacement during the study, and 37% required percutaneous endoscopic gastrostomy tube replacement. Most patients were on levodopa monotherapy. Patients maintained reductions in "off" time and increases in mean "on" time without dyskinesia from initial levodopa-carbidopa intestinal gel infusion to he study end point (P < 0.001; n 5 81). Activities of daily living and quality-of-life assessments demonstrated significant improvements that persisted through the study. Conclusions: This long-term study demonstrates sustained and clinically meaningful benefits from levodopacarbidopa intestinal gel in advanced PD patients.--

Safety of Levodopa-Carbidopa Intestinal Gel Treatment in Patients with Advanced Parkinson’s Disease Receiving ≥2000 mg Daily Dose of Levodopa

“…Data were collected from patients with advanced PD who participated in a 12-week, randomized, double-blind, active-controlled parallel-group study [9] (NCT00660387/NCT0357994) and either the subsequent 52-week open-label extension study [12] (NCT00360568) or a separate 54-week open-label study [10] (NCT00335153). Patients were then eligible to enroll in an ongoing open-label, continued-access multinational extension study [11] (NCT00660673) where they could continue treatment until the product was available locally. e enrollment period was from November 2009 through October 2012.…”

“…Levodopa-carbidopa intestinal gel (LCIG, also known as carbidopa-levodopa enteral suspension in the United States) was developed to deliver continuous administration of levodopa treatment via percutaneous endoscopic gastrojejunostomy (PEG-J), resulting in improved motor function and fewer drug fluctuations in patients with advanced PD. Results from subsequent clinical studies using this approach have demonstrated improvements in clinical outcomes, including significant improvements in "Off " time and "On" time without troublesome dyskinesia (TSD), quality of life, and improvements in activities of daily living [8][9][10][11][12]. Although there is robust evidence for the clinical benefit of LCIG in patients with advanced PD, there are no studies assessing the safety and efficacy of high doses (≥2000 mg), and information on the use of high-dose LCIG is limited.…”

“…ese studies provide the largest dataset with longterm follow-up of LCIG in patients with advanced PD to date. e dataset was stratified to provide insights into patient populations that require high-dose levodopa [8][9][10][11][12].…”

Parkinson's disease: A Review about Pathogenesis, Pharmaceutical Treatment and Experimental Models

“…Therefore, intestinal gel infusions of L-dopa support the concept of continuous DA receptor stimulation needed to prevent dyskinesias induced by L-dopa. 10,142 In addition to motor complications and nausea, many other adverse effects may be associated with Ldopa treatment. Hallucinations and confusion are the most adverse effects e in the elderly and in those with preexisting cognitive dysfunction.…”

“…8 DA precursor (L-dopa) was found to be qualified in alleviating the symptoms of PD and till now, the main PD management is the chronic oral administration of L-dopa. 9,10 With the discovery of a toxin-induced PD in humans in the early1980, the second advance in PD research came. An illicitly manufactured opiate contaminated with 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) whose users rapidly produced progressive, L-dopa-responsive parkinsonism like to what reported in sporadic PD.…”