Safety Of Levodopa-carbidopa Intestinal Gel Research Articles

Real-world effect of age on long-term effectiveness and safety of levodopa-carbidopa intestinal gel: post hoc analysis from the DUOGLOBE study

Real-world effect of age on long-term effectiveness and safety of levodopa-carbidopa intestinal gel: post hoc analysis from the DUOGLOBE study

Real-world Effect of Age on Long-term Effectiveness and Safety of Levodopa-Carbidopa Intestinal Gel: A Post Hoc Analysis From the Prospective, Multinational, Observational DUOGLOBE Study (P9-11.007)

Real-world Effect of Age on Long-term Effectiveness and Safety of Levodopa-Carbidopa Intestinal Gel: A Post Hoc Analysis From the Prospective, Multinational, Observational DUOGLOBE Study (P9-11.007)

Efficacy and safety of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients stratified by baseline Hoehn and Yahr stage

Background: Assess baseline disease severity efficacy of levodopa-carbidopa intestinal gel(LCIG) on motor fluctuations, non-motor symptoms(NMS), axial symptoms, and quality of life(QoL) in advanced Parkinson's disease(aPD) patients.

A post hoc comparison of levodopa-carbidopa intestinal gel daytime monotherapy vs polytherapy safety and efficacy in patients with advanced Parkinson's disease: Results from 6 phase 3/3b open-label studies

IntroductionAs Parkinson's disease (PD) progresses, the number/frequency of PD medications tend to increase, which is correlated with decreased patient compliance and suboptimal control of PD symptoms. We investigated efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) daytime monotherapy (with or without nighttime oral levodopa-carbidopa) compared with polytherapy (LCIG with ≥1 adjunctive PD therapy) in advanced PD patients. MethodsThis post hoc descriptive study compared LCIG stable daytime monotherapy with LCIG stable polytherapy in all six phase 3/3b open-label studies from both US and international sites; because of study design variability, pooling data for comparison was not appropriate. Efficacy assessments included PD diary data (mean change from baseline in “Off” time and “On” time with or without troublesome dyskinesia), mean Unified PD Rating Scale scores (Parts II and III), and 39-item Parkinson's Disease Questionnaire (PDQ-39) summary index. Adverse events were also assessed. ResultsOverall, LCIG daytime monotherapy and polytherapy demonstrated similar efficacy/safety profiles in advanced PD patients, regardless of treatment duration or population. LCIG monotherapy vs. polytherapy groups experienced similar mean decreases in “Off” time (4.6 vs. 4.1 h/day) and similar increases in “On” time without troublesome dyskinesia (4.6 vs. 4.1 h/day). In most studies, PDQ-39 summary index scores were reduced from baseline by ≥5 points, regardless of patient population or study duration. Adverse events not related to the procedure/device were similar in both groups. ConclusionOur data suggest that, for appropriate patients, LCIG monotherapy can provide a more simplified treatment option with similar efficacy and safety.

Safety of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinsonʼs Disease Patients: Interim Results of a U.S. Subset in the DUOGLOBE Observational Study

Introduction: Levodopa-carbidopa intestinal gel (LCIG) (also known in the US as carbidopa-levodopa enteral suspension [CLES]) is a long-term treatment option for advanced Parkinson's disease (PD) patients and administered via percutaneous gastrojejunostomy (PEG-J) and an external pump. Objective of this interim analysis in a US patient subset in the DUOGLOBE observational study was to investigate routine clinical practice of PEG-J insertion, component replacements of the device and associated safety/tolerability.2834_A Figure 1. Percentage of patients with number of component replacements based on type of proceduralist performing the PEG-J insertion occurring in the first 6 months of treatment.2834_B Figure 2. Summary of treatment-emergent Serious Adverse Events occurring in the first 6 months of treatment in a US patient subsetMethods: DUOGLOBE is an ongoing observational multi-country study with a 3 year follow-up. This interim analysis included patients recruited at 19 US sites who had at least the PEG-J insertion procedure performed. The safety profile of these patients was investigated regarding the type of proceduralist performing the PEG-J insertion, type of tubing used, frequency of tube replacements and Serious Adverse Events (SAEs) reported. This interim analysis was not powered for comparison between groups due to limited number of patients. Results: Twenty-seven US patients were included in the interim analysis. 16 (59%) had PEG-J insertion performed by a gastroenterologist (GI) with 13 (81%) completing the first 6 months of the study. 11 subjects (41%) had an interventional radiologist (IR) perform the procedure with 8 (73%) completing the first 6 months of the study. Out of the entire US subset, 81.5% of patients had no tube replacements during the first 6 months with overall similar percentages of subjects with 0/1/2/3 tube replacements between the two types of proceduralists (GI: 0-75%, 1-25%, 2-0%, 3-0%; IR: 0-90.9%, 1-0%, 2-9.1%, 3-0%) during the first 6 months of the study (figure 1). Of the 5 tube replacements, 4 were performed by a GI using AbbVie proprietary tubing and 1 was performed by an IR using non-AbbVie tubing. The incidence of treatment-emergent SAEs is summarized in Table 1. Conclusion: In this interim analysis of the US subset of a multi-country observational study with CLES, limited by small patient numbers, GIs more frequently performed PEG-J insertion than IRs with similar percentage of subjects completing the first 6 months of the study. Frequency of tube replacements and AEs leading to drug withdrawn were similar between GIs and IRs.

Safety and efficacy of levodopa-carbidopa intestinal gel: results from an open-label extension study in Japanese, Korean and Taiwanese patients with advanced Parkinson's disease.

Objectives:Levodopa-carbidopa intestinal gel (LCIG) was developed to reduce motor complications in Parkinson’s disease (PD) caused by pulsatile levodopa plasma concentrations following oral levodopa administration. Dyskinesia and ‘wearing off’ symptoms can vary between Asian and Caucasian patients with PD, thus highlighting the importance of assessing the effectiveness of LCIG in an Asian population. Efficacy and safety of LCIG were previously assessed in a 12-week open-label study; we report the efficacy and safety of at least 52 weeks of LCIG treatment in Japanese, Taiwanese, and Korean patients with advanced PD in the ongoing extension study.Methods:In this interim analysis of a phase III, open-label, multicenter extension study in Japan, South Korea, and Taiwan [ClinicalTrials.gov identifier: NCT02082249/JapiCTI-142482], the mean change from baseline to final visit in ‘off’ time, as reported in the PD symptom diary, was normalized to a 16-h waking day. Changes in Parkinson’s Disease Questionnaire-39 (PDQ-39) summary index and domains scores were also analyzed. Adverse events (AEs) were recorded.Results:Of the 28 patients enrolled (21 Japanese, 3 Taiwanese, 4 Korean), 27 completed at least 52 total weeks of treatment, and 25 patients were continuing in the study at data cutoff. The mean [standard deviation (SD)] ‘off’ time was significantly reduced by 4.6 (3.1) h/day (p < 0.001, n = 28). Patients experienced significant improvements in quality of life, as recorded by the mean change from baseline in PDQ-39 summary index (p < 0.001). All patients had at least one AE; three patients (11%) discontinued due to an AE. There were two deaths (sepsis and drowning), both of which the investigator considered unrelated to LCIG treatment.Conclusions:These data suggest that LCIG treatment is efficacious, safe, and well tolerated in Japanese, Taiwanese, and Korean patients with advanced PD, thus confirming the consistency of LCIG treatment in patients with advanced PD.

Global long-term registry on efficacy and safety of levodopa-carbidopa intestinal gel in advanced Parkinson’s disease patients (GLORIA) – final results in a subgroup of patients with dyskinesia at baseline (S4.001)

Global long-term registry on efficacy and safety of levodopa-carbidopa intestinal gel in advanced Parkinson’s disease patients (GLORIA) – final results in a subgroup of patients with dyskinesia at baseline (S4.001)

Efficacy and safety of levodopa-carbidopa intestinal gel from a study in Japanese, Taiwanese, and Korean advanced Parkinson's disease patients.

In a previous multinational, randomized, double-blind, double-dummy study, levodopa–carbidopa intestinal gel (LCIG) was tolerable and significantly improved ‘off’ time in advanced Parkinson’s disease (PD) patients. However, efficacy and safety in the Asian population has not yet been demonstrated. In this open-label study, efficacy and safety of LCIG were assessed in Japanese, Korean, and Taiwanese advanced PD patients with motor complications not adequately controlled by available PD medication. The patients were treated with LCIG monotherapy for 12 weeks. The primary end point was the mean change from baseline to week 12 in ‘off’ time, as reported in the PD Symptom Diary, normalized to a 16 h waking day and analyzed by a mixed-model repeated-measures analysis. Adverse events (AEs) were recorded. Thirty-one patients were enrolled (23 Japanese, 4 Taiwanese, 4 Korean) and 28 (90%) completed the study. For those who completed the study, the mean (s.d.) total daily levodopa dose from LCIG was 1,206.3 (493.6) mg/day at final visit (n=28); last observation carried forward (n=30) was 1,227.6 (482.8) mg/day. There was a significant mean change (s.d.) of −4.6 (3.0) hours of ‘off’ time from baseline (mean (s.d.)=7.4 (2.3)) to week 12 (n=29), P<0.001. All the patients had an AE, with the most frequently reported being incision site pain (42%); 1 (3.2%) discontinued treatment because of an AE and later died because of sepsis, which the investigator considered unrelated to LCIG treatment. These results suggest that LCIG is efficacious and tolerable in Japanese, Taiwanese, and Korean advanced PD patients.

Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel from an Open-Label Study in Japanese, Taiwanese, and Korean Patients with Advanced Parkinson’s Disease (P5.362)

Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel from an Open-Label Study in Japanese, Taiwanese, and Korean Patients with Advanced Parkinson’s Disease (P5.362)

Gastrointestinal safety of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients: GLORIA long-term registry interim results

Gastrointestinal safety of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients: GLORIA long-term registry interim results

Gastrointestinal safety of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients: GLORIA long-term registry interim results

Gastrointestinal safety of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients: GLORIA long-term registry interim results

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (I3-3B)

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (I3-3B)

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (P3.004)

Global Long-Term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results on Non-Motor Symptoms (P3.004)

Global Long-term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results in a Subgroup of Patients with Dyskinesia at Baseline (P1.192)

Global Long-term Registry on Efficacy and Safety of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced Parkinson’s Disease in Routine Care (GLORIA) - Interim Results in a Subgroup of Patients with Dyskinesia at Baseline (P1.192)

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study

Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥ 30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4.04 h (SE 0.65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2.14 h (0.66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference -1.91 h [95% CI -3.05 to -0.76]; p=0.0015). Mean on-time without troublesome dyskinesia increased by 4.11 h (SE 0.75) in the intestinal gel group and 2.24 h (0.76) in the immediate-release oral group (difference 1.86 [95% CI 0.56 to 3.17]; p=0.0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. AbbVie.