Long-Term Safety and Maintenance of Efficacy of Levodopa-Carbidopa Intestinal Gel: An Open-Label Extension of the Double-Blind Pivotal Study in Advanced Parkinson's Disease Patients

Abstract

Background: Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously via intrajejunal percutaneous gastrostomy tube. Objective: To examine long-term safety, efficacy and quality of life of LCIG in an open-label extension study. Methods: Patients received 52 weeks of open-label LCIG treatment following a 12-week double-blind, double-dummy trial in which they were randomized to either LCIG or immediate-release oral levodopa-carbidopa. Patient cohort designation was by receipt of LCIG in the preceding trial randomization (continuing-LCIG vs. LCIG-naïve patients). Results: Sixty-two of 66 subjects in the double-blind proceeded to the open-label extension. Most subjects (95%) reported ≥1 adverse event (AE); only 3 subjects (4.8%) discontinued due to AEs. AE incidence declined gradually over 52 weeks. Serious AEs were reported by 23%. LCIG-naïve patients (N = 29) showed a decrease in "Off" time and an increase in "On" time without troublesome dyskinesia (change from baseline to final visit in mean [SD] hours = −2.34 [2.78] P < 0.001 and 2.19 [3.70] P = 0.005, respectively), while continuing-LCIG patients (N = 33) showed sustained "Off" time duration and further improvement in "On" time without troublesome dyskinesia (−0.42 [2.67] P = 0.377 and 1.00 [2.58] P = 0.036, respectively). The majority of patients in both groups (LCIG-naïve, continuing-LCIG, respectively) were rated 'Much Improved' or 'Very Much Improved' at final visit on the Clinical Global Impression-Improvement scale (69.0%, 69.7%). Conclusions: Continuing-LCIG patients continued to derive benefit from LCIG while the magnitude of improvement among LCIG-naïve patients was similar to that observed for patients on LCIG in the preceding double-blind study. The overall AE profile was consistent with previous phase 3 clinical trials involving the LCIG system.

An Observational Study of the Effect of Levodopa–Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson’s Disease Patients

“…The safety results were consistent with the established safety profile of LCIG [11, 12, 17]; no new safety concerns were reported or detected. The most common AEs were related to maintenance of the stoma site.…”

“…These results extend current findings, which have focused primarily on the effect of LCIG on motor complications [10–12, 14]. As it has recently been suggested that there is a relationship between improvements in motor UPDRS and NMSS scores [18], assessing the effect of both motor and non-motor symptoms on quality of life will be a boon to patients with advanced PD.…”

“…Results from this prospective, multicenter, observational study showed significant improvements in activities of daily living, motor and non-motor symptoms, and quality-of-life scores, with safety results in accord with the known safety profile of LCIG [11, 12, 17]. These results extend current findings, which have focused primarily on the effect of LCIG on motor complications [10–12, 14].…”

Effect of levodopa-carbidopa intestinal gel on resting tremors in patients with advanced Parkinson’s disease

“…Observed improvements in tremors with LCIG treatment could be because levodopa/carbidopa is dosed continuously, resulting in reduced plasma levodopa fluctuations when compared with oral dosing, thus allowing patients to achieve the more effective dose needed to control resting tremors. Improved tolerability (e.g., fewer dyskinesias) seen with continuously dosed levodopa allows for larger doses of levodopa, if necessary, when compared with oral therapy; 5,8,9 the overall higher dose of levodopa/carbidopa administered to patients in this study compared with typical oral dosing may have improved control of resting tremors. However, the dose of levodopa/carbidopa increased to a similar degree in the mild and significant resting tremor subgroups, yet there was a larger improvement in resting tremor in the significant baseline tremor subgroup.…”

“…4 LCIG treatment via PEG-J significantly reduces ‘Off’ time and significantly increases ‘On’ time without troublesome dyskinesia (TSD). 5,8,9 …”