Effectiveness Of Levodopa-carbidopa Intestinal Gel Research Articles

Effects of Levodopa-Carbidopa Intestinal Gel Compared with Optimized Medical Treatment on Nonmotor Symptoms in Advanced Parkinson's Disease: INSIGHTS Study.

Nonmotor symptoms (NMS) are common in advanced Parkinson's disease (APD) and reduce health-related quality of life. The aim of the study was to evaluate levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) on NMS in APD. INSIGHTS was a phase 3b, open-label, randomized, multicenter study in patients with APD (LCIG or OMT, 26 weeks) (NCT02549092). Primary outcomes assessed were total NMS (NMS scale (NMSS) and PD sleep scale (PDSS-2)). Key secondary outcomes included the Unified PD Rating Scale (UPDRS) Part II, Clinical Global Impression of Change (CGI-C), and PD Questionnaire-8 (PDQ-8). Additional secondary measures of Patient Global Impression of Change (PGIC), King's PD Pain Scale (KPPS), and Parkinson Anxiety Scale (PAS) also were evaluated. Finally, safety was assessed. Out of 89 patients randomized, 87 were included in the analysis (LCIG, n = 43; OMT, n = 44). There were no significant differences in NMSS or PDSS-2 total score changes (baseline to Week 26) between LCIG and OMT; within-group changes were significant for NMSS (LCIG, p < 0.001; OMT, p = 0.005) and PDSS-2 (LCIG, p < 0.001; OMT, p < 0.001). Between-group treatment differences were nominally significant for UPDRS Part II (p = 0.006) and CGI-C (p < 0.001) at Week 26 in favor of LCIG; however, statistical significance could not be claimed in light of primary efficacy outcomes. PGIC (Week 26) and KPPS (Week 12) scores were nominally significantly reduced with LCIG versus OMT (p < 0.001; p < 0.05). There were no significant differences in PDQ-8 or PAS. Adverse events (AEs) were mostly mild to moderate; common serious AEs were pneumoperitoneum (n = 2) and stoma-site infection (n = 2) (LCIG). There were no significant differences between LCIG versus OMT in NMSS or PDSS-2; both LCIG and OMT groups significantly improved from baseline. AEs were consistent with the known safety profile.

Effects of Levodopa-Carbidopa Intestinal Gel on Dyskinesia and Non-Motor Symptoms Including Sleep: Results from a Meta-Analysis with 24-Month Follow-Up.

In advanced Parkinson's disease (PD), dyskinesias and non-motor symptoms such as sleep dysfunction can significantly impair quality of life, and high-quality management is an unmet need. To analyze changes in dyskinesia and non-motor symptoms (including sleep) among studies with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. A comprehensive literature review identified relevant studies examining LCIG efficacy. Outcomes of interest were dyskinesia (UDysRS, UPDRS IV item 32), overall non-motor symptoms (NMSS), mentation/behavior/mood (UPDRS I), and sleep/daytime sleepiness (PDSS-2, ESS). The pooled mean (95% confidence interval) change from baseline per outcome was estimated for each 3-month interval with sufficient data (i.e., reported by≥3 studies) up to 24 months using a random-effects model. Seventeen open-label studies evaluating 1243 patients with advanced PD were included. All outcomes of interest with sufficient data for meta-analysis showed statistically significant improvement within 6 months of starting LCIG. There were statistically significant improvements in dyskinesia duration as measured by UPDRS IV item 32 at 6 months (-1.10 [-1.69, -0.51] h/day) and 12 months (-1.35 [-2.07, -0.62] h/day). There were statistically and clinically significant improvements in non-motor symptoms as measured by NMSS scores at 3 months (-28.71 [-40.26, -17.15] points). Significant reduction of NMSS burden was maintained through 24 months (-17.61 [-21.52, -13.70] points). UPDRS I scores significantly improved at 3 months (-0.39 [-0.55, -0.22] points). Clinically significant improvements in PDSS-2 and ESS scores were observed at 6 and 12 months in individual studies. Patients with advanced PD receiving LCIG showed significant sustained improvements in the burden of dyskinesia and non-motor symptoms up to 24 months after initiation.

Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel.

Background:It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated.Objective:Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms.Methods:This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms.Results:A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time.Conclusion:Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.

The Cost Effectiveness of Levodopa-Carbidopa Intestinal Gel in the Treatment of Advanced Parkinson's Disease in England.

BackgroundParkinson’s disease is a progressive neurodegenerative disease, which significantly impacts patients’ quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson’s disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory.ObjectiveWe aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson’s disease in England, using real-world data.MethodsA Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson’s disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted.ResultsTotal costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG.ConclusionsThe base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01132-y.

Patient and caregiver outcomes with levodopa-carbidopa intestinal gel in advanced Parkinson\u2019s disease

Levodopa-carbidopa intestinal gel (LCIG) has shown to be efficacious in motor and non-motor symptoms (NMS). Nevertheless, studies with patient Quality of Life (QoL) as a primary endpoint are scarce. To assess the effect of LCIG on Advanced Parkinson’s Disease (APD) patients QoL. Secondarily, the impact on motor symptoms and NMS, emotional well-being, treatment satisfaction, and caregiver QoL, stress, disease burden, anxiety, depression, and work impairment were also investigated. In this prospective, 6-month multicenter postmarketing observational study, LCIG was administered to 59 patients with APD. Endpoints were assessed using validated scales and questionnaires. LCIG significantly improved patient QoL (PDQ-39 mean change ± standard deviation from baseline, −12.8 ± 14.6; P < 0.0001), motor symptoms (UPDRS-III in “On,” −6.5 ± 11.8; P = 0.0002), NMS (NMSS, −35.7 ± 31.1; P < 0.0001), mood (Norris/Bond-Lader VAS, −6.6 ± 21.1; P = 0.0297), fatigue (PFS-16, −0.6 ± 1.0; P = 0.0003), depression (BDI-II, −5.1 ± 9.4; P = 0.0002), anxiety (BAI, −6.2 ± 9.6; P < 0.0001), and patient treatment satisfaction (SATMED-Q, 16.1 ± 16.8; P < 0.0001). There were significant correlations between the change from baseline to 6 months between PDQ-39 and UPDRS-IV, NMSS, BAI, BDI-II, AS, and PFS-16 scores, and Norris/Bond-Lader alertness/sedation factor. Caregiver anxiety also improved (Goldberg anxiety scale, −1.1 ± 1.0; P = 0.0234), but the clinical relevance of this finding is questionable. The serious adverse events reported were similar to those previously described for LCIG. In patients with APD, LCIG improves QoL, motor symptoms and NMS, emotional well-being, and satisfaction with the treatment. Improvement in patient QoL is associated with improvements in motor complications, NMS, anxiety, depression, apathy and fatigue. Improvements in patients’ QoL does not correspond with improvements in caregivers’ QoL or burden.

Levodopa‐Carbidopa Intestinal Gel Reduces Dyskinesia in Parkinson's Disease in a Randomized Trial

ABSTRACTBackgroundThere are limited data regarding the effectiveness of levodopa‐carbidopa intestinal gel (LCIG) for dyskinesia.ObjectiveCompare the effectiveness of LCIG versus oral optimized medical treatment (OMT) for dyskinesia in patients with advanced Parkinson's disease (PD) using the Unified Dyskinesia Rating Scale (UDysRS).MethodsThis phase 3b, open‐label, multicenter, 12‐week, interventional study (NCT02799381) randomized 63 LCIG naïve patients with advanced PD (UDysRS ≥30) to LCIG (N = 30) or OMT (N = 33) treatment. Dyskinesia impact was assessed at baseline through week 12 using the UDysRS. PD‐related motor and non‐motor symptoms, and quality of life (QoL) were also assessed.ResultsDyskinesias measured by UDysRS were significantly reduced in the LCIG group (n = 24; −17.37 ± 2.79) compared with the OMT group (n = 26; −2.33 ± 2.56) after 12 weeks (−15.05 ± 3.20; 95% CI, −21.47 to −8.63; P < 0.0001). At week 12, LCIG versus OMT also demonstrated significant improvements in “On” time without troublesome dyskinesia (P = 0.0001), QoL (P < 0.0001), global impression of change (P < 0.0001), activities of daily living (P = 0.0006), and Unified Parkinson's Disease Rating Scale (UPDRS) Part III (P = 0.0762). Treatment‐emergent adverse events were reported in 27 (44.3%) patients (LCIG, 18 [64.3%]; OMT, 9 [27.3%]). Serious adverse events occurred in 2 (7.1%) LCIG‐treated patients.ConclusionsLCIG significantly reduced dyskinesia compared with OMT. LCIG showed efficacy for treatment of troublesome dyskinesia in patients with advanced PD while demonstrating benefits in both motor and non‐motor symptoms and QoL. © 2021 AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

Long-term effectiveness of levodopa-carbidopa intestinal gel on motor and non-motor symptoms in advanced Parkinson\u2019s disease: results of the Italian GLORIA patient population

IntroductionThe GLORIA registry included 375 advanced Parkinson’s disease (PD) patients and evaluated the efficacy and safety of a 24-month levodopa-carbidopa intestinal gel (LCIG) treatment in routine medical care. This analysis focuses on the Italian population, 60 patients treated with LCIG in 7 specialised PD care centres.MethodsHours of “Off” and “On” time were assessed with a modified version of the Unified Parkinson’s Disease Rating Scale (UPDRS) part IV items 39 and 32. Motor fluctuations, dyskinesia, non-motor symptoms, quality of life and safety were evaluated.ResultsOverall, 42 (70%) out of 60 patients completed the registry. LCIG treatment reduced “Off” time (− 3.3 ± 2.7 h at month 24 (M24), P < 0.0001), increased “On” time with dyskinesia (− 2.6 ± 5.2 h at M12, P = 0.0160), and improved UPDRS II and UPDRS III total scores at M24 (− 4.5 ± 10.6, P = 0.0333 and − 4.9 ± 11.7, P = 0.0229, respectively), Non-Motor Symptom Scale (NMSS) total score (− 21.8 ± 28.5, P < 0.0001) and Parkinson’s Disease Questionnaire-8 item (PDQ-8) total score (− 12.5 ± 23.9, P = 0.0173) versus previous oral therapy. Adverse drug reactions (ADR) possibly or probably related to treatment were reported in 16 (28.6%) patients. Decreased weight (7.1%), polyneuropathy (7.1%) and abdominal pain (5.4%) were the most frequent ADRs while device malfunction (5.4%) and medical device change (5.4%) were the most reported device complaints.ConclusionsLCIG improved motor fluctuations, non-motor symptoms and quality of life over 24 months while tolerability was consistent with the established safety profile.

Video analysis of long-term effects of levodopa-carbidopa intestinal gel on gait and posture in advanced Parkinson's disease.

Gait and posture parameters of ten advanced Parkinson's disease (PD) patients were assessed before and after starting levodopa-carbidopa intestinal gel (LCIG) treatment by means of both objective video analysis and clinical assessment. After 3years of treatment, gait and posture remained stable. A slower gait velocity at baseline significantly correlates with a higher axial and motor severity at follow-up. This pilot study suggests that validated video analysis software may support the clinical assessment of axial signs in PD patients who are candidates for device-aided therapies.

Effect of Intestinal Levodopa-Carbidopa Infusion on Pharyngeal Dysphagia: Results from a Retrospective Pilot Study in Patients with Parkinson's Disease.

Background Pharyngeal dysphagia is a common symptom of Parkinson's disease (PD) leading to severe complications. PD-related pharyngeal dysphagia (PDrPD) may significantly improve in up to half of patients following acute oral levodopa challenge. Objective The aim of this study was to investigate the effects of levodopa-carbidopa intestinal gel (LCIG) on PDrPD. Methods Forty-five PD patients under LCIG treatment were available for retrospective analysis. In all patients with PDrPD who underwent flexible endoscopic evaluation of swallowing (FEES) in the clinical “on-state” both before and after implementation of LCIG treatment, FEES videos were systematically reassessed. PDrPD was characterized using a PD-specific FEES score evaluating premature bolus spillage, penetration/aspiration, and pharyngeal residue. Further, the duration of white-out was assessed, as a parameter for pharyngeal bradykinesia. Results Eleven patients with PDrPD (mean age 74.6 ± 4.4 years; mean Hoehn and Yahr stage 3.8 ± 0.6) received FEES both before and after the onset of LCIG treatment. The mean swallowing score improved from 14.9 ± 7.3 to 13.0 ± 6.9 after implementation of LCIG; however, this difference was not significant (p=0.312). Premature bolus spillage decreased significantly (p=0.002) from 5.4 ± 1.1 to 3.6 ± 1.0, and white-out duration decreased significantly (p=0.002) from 984 ± 228 ms to 699 ± 131 ms after implementation of LCIG. Conclusions LCIG may affect PDrPD and reduce premature bolus spillage and pharyngeal bradykinesia. Future studies with larger sample sizes are required to follow-up on these pilot results and identify which factors predict a good response of PDrPD to LCIG treatment.

The effect of functional status impairment on nursing home admission risk among patients with advanced Parkinson’s disease

Aims: To estimate the relationship between functional status (FS) impairment and nursing home admission (NHA) risk in Parkinson’s disease (PD) patients, and quantify the effect of advanced PD (APD) treatment on NHA risk relative to standard of care (SoC).Materials and methods: PD patients were identified in the Medicare Current Beneficiary Survey (MCBS) (1992–2010). A working definition based on the literature and clinical expert input determined APD status. A logit model estimated the relationship between FS impairment and NHA risk. The effect of levodopa-carbidopa intestinal gel (LCIG) on NHA risk relative to SoC was simulated using clinical trial data (control: optimized oral levodopa-carbidopa IR, ClinicalTrials.gov NCT00660387 and NCT0357994).Results: Non-advanced PD and APD significantly increased NHA risk when controlling for demographics (p < 0.01). APD status was no longer significant after controlling for FS limitations, implying that FS limitations explain the increased NHA risk in APD patients. Reduced impairment in FS in patients with APD treated with LCIG reduced risk of NHA by 13.5% relative to SoC.Limitations: This study applies clinical trial results to real-world data. LCIG treatment might have a different effect on NHA risk for the nationally representative population than the effect measured in the trial. Both data sources employ different instruments to measure FS, instrument wording and study follow-up differed, which might bias our estimates. Finally, there lacks consensus on a definition of APD. The prevalence of APD in this study is high, perhaps due to the specific definition used.Conclusions: Patients with APD experience a higher risk in NHA than those with non-advanced disease. This increased risk in NHA in patients with APD is explained by greater limitations in FS. The relative reduction in risk of NHA for the APD population treated with LCIG is quantitatively similar to doubling Medicaid home care services.

Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study

BackgroundTreatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). However, adverse events (AEs) are frequent. ObjectiveTo describe AEs associated with LCIG treatment and the main reasons for treatment discontinuation. We also looked for factors that were potentially predictive of serious AEs and assessed the effectiveness of and satisfaction with LCIG. MethodWe retrospectively analyzed data on AEs in patients treated with LCIG at a French university medical center. For patients still receiving treatment at last follow-up, effectiveness was assessed according to the Clinical Global Impression (CGI) scale and the Movement Disorders Society – Unified Parkinson's Disease Rating Scale motor score. ResultsOf the 63 patients treated with LCIG for a mean (range) of 19 months (8–47), 57 (90%) experienced at least one AE (340 AEs in total). Most of the AEs (in 69.8% of the patients) were related to percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) or affected the gastrointestinal tract (granuloma, leakage, or a local infection). Device-related AEs (such as PEG-J removal and device occlusion) were frequent (in 63.5% of patients). Forty-three patients (68%) required at least one additional endoscopic procedure. Dopatherapy-related AEs occurred in 30 patients (48%). Most of the AEs occurred long after treatment initiations, and only a small proportion led to discontinuation. On the CGI scale, 53 patients (84.4%) considered that their condition had improved during LCIG treatment. ConclusionDespite the high frequency of AEs, patients with advanced PD gain clinical benefit from treatment with LCIG. This treatment requires a competent, multidisciplinary team on site.

Impact of Disease Duration in Effectiveness of Treatment with Levodopa-Carbidopa Intestinal Gel and Factors Leading to Discontinuation.

Levodopa-carbidopa intestinal gel (LCIG) is effective in the treatment of advanced Parkinson's disease (PD). However, the patients' profile that might benefit from treatment with LCIG has not been characterized. This retrospective study explored the influence of disease duration (DD) on the effectiveness of LCIG and identified factors associated with treatment discontinuation in a cohort of advanced PD patients. Patients initiating LCIG therapy between Jan-2006 and Dec-2011 in 18 Spanish centers were included. Effectiveness in treating motor symptoms (MSs), non-motor symptoms (NMSs), and adverse events (AEs) occurrence was compared in DD≥10 or <10 years and LCIG continuation/discontinuation groups. Factors associated with LCIG discontinuation were evaluated using univariate and multivariate analyses. Overall, 177 PD patients were included (52.5% male; mean age 70.6±8.4 years; mean LCIG duration 35.6±18.6 months). Patients with DD≥10 years (n = 125) experienced less reduction in "off" time (-29%) than those with DD <10 years (-38%; n = 51; p = 0.021), and reported more severe AEs (32.8% vs. 17.6%; p = 0.043). DD did not significantly influence changes in NMSs or discontinuation rates. Fifty-four patients discontinued LCIG therapy, factors associated with discontinuation were higher percentages of waking day in the "off" state (OR, 1.028; 95% CI, 1.002-1.055; p = 0.0360) and in the "on" state with troublesome dyskinesia (OR, 1.032; 95% CI, 1.002-1.064; p = 0.0376) at baseline. Advanced PD patients with DD <10 years might benefit more from treatment with LCIG than patients with a longer DD. Although MSs severity at baseline was statistically associated with LCIG discontinuation, the probability was very low with little clinical significance.

Sleep Quality and Levodopa Intestinal Gel Infusion in Parkinson’s Disease: A Pilot Study

Background Sleep problems in patients with advanced Parkinson's disease (PD) have a deleterious impact on quality of life. Objective To assess the effect of levodopa-carbidopa intestinal gel (LCIG) infusion on sleep quality in advanced PD patients. Methods Seven patients participated in a prospective pilot study. Before and after 6 months of LCIG infusion, an overnight polysomnography was performed and the Epworth Sleepiness Scale, fatigue scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory, and the Hamilton Anxiety Rating Scale were administered. Results PSG showed low sleep efficiency. REM sleep without atony was found in 5 patients. After 6 months of LCIG infusion, the percentage of REM sleep decreased as well as the number of arousals especially due to reduction of spontaneous arousals and periodic leg movements during REM sleep, but differences were not statistically significant. Also, scores of all study questionnaires showed a tendency to improve. Conclusion The results show a trend toward an improvement of sleep quality after 6 months of LCIG infusion, although differences as compared to pretreatment values were not statistically significant. The sleep architecture was not modified by LCIG. Further studies with larger study samples are needed to confirm these preliminary findings.

Effect of levodopa-carbidopa intestinal gel in advanced Parkinson’s disease patients

Effect of levodopa-carbidopa intestinal gel in advanced Parkinson’s disease patients

Effect of Levodopa-carbidopa Intestinal Gel on Non-motor Symptoms in Patients with Advanced Parkinson's Disease.

BackgroundLevodopa‐carbidopa intestinal gel (LCIG; carbidopa‐levodopa enteral suspension in the United States), delivered via percutaneous gastrojejunostomy (PEG‐J) and titrated in the inpatient setting, is an established treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. However, long‐term prospective data on the efficacy of LCIG on non‐motor symptoms and the safety of outpatient titration are limited.MethodsIn this 60‐week, open‐label phase 3b study, LCIG titration was initiated in an outpatient setting following PEG‐J placement in PD patients. The efficacy of LCIG on motor and non‐motor symptoms, quality of life, and safety was assessed.ResultsThirty‐nine patients were enrolled in the study and 28 patients completed the treatment. A majority of patients (54%) completed outpatient titration within the first week of LCIG infusion. LCIG led to significant reductions from baseline in Non‐Motor Symptom Scale (NMSS) total score (least squares mean ± SE = −17.6 ± 3.6, P < 0.001) and 6 of the NMSS domain scores (sleep/fatigue, attention/memory, gastrointestinal tract, urinary, sexual function, miscellaneous) at week 12. These reductions were maintained at week 60 with the exception of the urinary domain. “Off” time (−4.9 ± 0.5 hours/day, P < 0.001) and “On” time without troublesome dyskinesia (−4.3 ± 0.6 hours/day, P < 0.001) were improved at week 60. Adverse events (AEs) were reported in 37 (95%) patients.Conclusions LCIG treatment led to reductions in non‐motor symptom burden and motor fluctuations in advanced PD patients. The safety profile was consistent with previous studies that used inpatient titration and outpatient titration did not appear to pose additional risk.

Effect of levodopa-carbidopa intestinal gel on dyskinesia: design of an open-label, randomized multicenter 12-week study in advanced Parkinson’s disease patients (P1.024)

Effect of levodopa-carbidopa intestinal gel on dyskinesia: design of an open-label, randomized multicenter 12-week study in advanced Parkinson’s disease patients (P1.024)

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

Resting tremors occur in more than 70% of patients with advanced Parkinson’s disease (PD). PD patients with resting tremors are typically treated with oral dopaminergic therapy or non-dopaminergic agents. However, treatment response with these medications is inconsistent and often unsatisfactory. Levodopa-carbidopa intestinal gel (LCIG, also known in the United States as carbidopa-levodopa enteral suspension (CLES)), administered continuously by a portable pump via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube, significantly improves motor complications in patients with advanced PD. This was a post hoc analysis of a large phase 3, 12-month, open-label study evaluating long-term safety and efficacy of LCIG via PEG-J tube (NCT00335153). Unified Parkinson’s Disease Rating Scale Part III Question 20 total scores at baseline, measuring resting tremors, were used to stratify patients into three subgroups (none, mild, or significant baseline resting tremors). Out of 354 enrolled patients, 286 had baseline and post-PEG-J assessments of resting tremors and were included in this analysis. At baseline the majority of patients (69%) had no resting tremors, whereas 13% had mild resting tremors, and 18% had significant resting tremors. A complete resolution in resting tremors after 12 months of LCIG treatment was reported for 78% and 70% of patients with mild and significant baseline resting tremors, respectively. Improvements in motor complications and quality of life occurred regardless of degree of baseline resting tremors. LCIG may provide more consistent and sustained improvements in resting tremors that were not well-controlled with optimized oral medication among patients with advanced PD.

Effect of Levodopa-Carbidopa Intestinal Gel on Resting Tremor in Patients with Advanced Parkinson’s Disease (P2.344)

Effect of Levodopa-Carbidopa Intestinal Gel on Resting Tremor in Patients with Advanced Parkinson’s Disease (P2.344)

Effect of levodopa-carbidopa intestinal gel on dyskinesia in advanced Parkinson's disease patients.

ABSTRACTObjectiveThe purpose of this study was to assess the effect of levodopa‐carbidopa intestinal gel (carbidopa‐levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia.MethodsPost hoc analyses of patient data from a 12‐week, randomized, double‐blind study and a 54‐week open‐label study were performed. Efficacy was assessed in the subgroup of patients defined by ≥1 hour of “on” time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n = 11 levodopa‐carbidopa intestinal gel, n = 12 oral levodopa‐carbidopa; open label: n = 144 levodopa‐carbidopa intestinal gel). The changes in “off” time, “on” time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa‐carbidopa intestinal gel were analyzed.ResultsAlthough not significantly different from oral levodopa treatment (P > .05) in the double‐blind study, levodopa‐carbidopa intestinal gel treatment resulted in a reduction from baseline in “on” time with troublesome dyskinesia (mean [standard deviation] hours: baseline = 3.1 [1.7], change from baseline to final = −1.8 [1.8], P = .014), increase in “on” time without troublesome dyskinesia (baseline = 7.4 [2.2], change = 4.4 [3.6], P = .004), and decrease in “off” time (baseline = 5.5 [1.3], change = −2.7 [2.8], P = .015). Similar trends were found in the open‐label study. An increase in levodopa‐carbidopa intestinal gel dose was not significantly correlated with increased “on” time with troublesome dyskinesia in either study (double blind: r = −.073, P = .842; open label: r = −0.001, P = .992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure.ConclusionOur exploratory analyses suggest that optimizing levodopa delivery with levodopa‐carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society

Effects of levodopa-carbidopa intestinal gel on non-motor symptoms and safety of outpatient titration: A new phase 3 study in patients with advanced Parkinson's disease

Effects of levodopa-carbidopa intestinal gel on non-motor symptoms and safety of outpatient titration: A new phase 3 study in patients with advanced Parkinson's disease