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Journal of Parkinson's Disease 2023Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD). (Observational Study)
Observational Study
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD).
OBJECTIVE
To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson's Disease - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713).
METHODS
DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care. The primary endpoint was change in patient-reported "Off" time to Month 36. Safety was assessed by monitoring serious adverse events (SAEs).
RESULTS
Significant improvements in "Off" time were maintained over 3 years (mean [SD]: -3.3 hours [3.7]; p < 0.001). There were significant improvements to Month 36 in total scores of the Unified Dyskinesia Rating Scale (-5.9 [23.7]; p = 0.044), Non-Motor Symptoms Scale (-14.3 [40.5]; p = 0.002), Parkinson's Disease Sleep Scale-2 (-5.8 [12.9]; p < 0.001), and Epworth Sleepiness Scale (-1.8 [6.0]; p = 0.008). Health-related quality of life and caregiver burden significantly improved through Months 24 and 30, respectively (Month 24, 8-item Parkinson's Disease Questionnaire Summary Index, -6.0 [22.5]; p = 0.006; Month 30, Modified Caregiver Strain Index, -2.3 [7.6]; p = 0.026). Safety was consistent with the well-established LCIG profile (SAEs: 54.9% of patients; discontinuations: 54.4%; discontinuations due to an adverse event: 27.2%). Of 106 study discontinuations, 32 patients (30.2%) continued LCIG outside the study.
CONCLUSION
DUOGLOBE demonstrates real-world, long-term, reductions in motor and non-motor symptoms in patients with aPD treated with LCIG.
Topics: Humans; Levodopa; Carbidopa; Parkinson Disease; Antiparkinson Agents; Prospective Studies; Quality of Life; Drug Combinations; Gels
PubMed: 37302039
DOI: 10.3233/JPD-225105 -
Therapeutic Delivery Jul 2019Accordion Pill (AP) is a novel gastric-retention oral delivery platform based on folded multilayer films (Intec Pharma, Jerusalem, Israel). Phase II clinical trials have... (Review)
Review
Accordion Pill (AP) is a novel gastric-retention oral delivery platform based on folded multilayer films (Intec Pharma, Jerusalem, Israel). Phase II clinical trials have evaluated gastric retention and pharmacokinetics (PK) of AP in healthy volunteers and efficacy and safety of AP containing carbidopa and levodopa (AP-CD/LD) in patients with Parkinson's disease (PD). AP was retained in the stomach for approximately 8 h, without special meal requirements. AP-CD/LD demonstrated improved absorption, more stable levodopa exposure and improved ON time compared with immediate-release CD/LD in advanced PD patients. AP provides a novel treatment platform for improving PK and efficacy for drugs with narrow absorption windows or poor solubility. Furthermore, AP allows multiple drug release profiles in a single capsule and can provide fixed-dose combinations.
Topics: Administration, Oral; Carbidopa; Delayed-Action Preparations; Gastrointestinal Tract; Half-Life; Humans; Levodopa; Parkinson Disease; Solubility
PubMed: 31203723
DOI: 10.4155/tde-2018-0067 -
The Medical Letter on Drugs and... Aug 2015
Review
Topics: Antiparkinson Agents; Carbidopa; Chemistry, Pharmaceutical; Drug Administration Routes; Drug Combinations; Drug Costs; Humans; Levodopa; Motor Activity; Parkinson Disease; Treatment Outcome
PubMed: 26218794
DOI: No ID Found -
Ideggyogyaszati Szemle Jan 2019For the treatment of advanced Parkinson's disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary.... (Review)
Review
For the treatment of advanced Parkinson's disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary. Although they may have similar impact on the health-related quality of life and disabilities associated with the disease, they have different indications, and inclusion- and exclusion criteria. Consequently, the patient population treated with DBS and LCIG may be different. In the present review, the authors try to help the process of selection of the optimal device-aided therapy for the patients with advanced Parkinson's disease.
Topics: Antiparkinson Agents; Carbidopa; Deep Brain Stimulation; Drug Combinations; Gels; Humans; Hungary; Levodopa; Parkinson Disease; Quality of Life
PubMed: 30785241
DOI: 10.18071/isz.72.0005 -
Journal of Neural Transmission (Vienna,... Nov 2023This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's... (Review)
Review
This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's disease (PD) possibly eligible for device-aided therapies (DATs). For the available screening tools, we describe the target therapies (subtypes of DAT), development methods, validation data, and their use in clinical practice. In addition, the historical background and potential utility of these screening tools are discussed. The challenges in developing and validating these tools are also addressed, taking into account the differences in population, the local health care organization, and resource availability.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Carbidopa; Levodopa; Drug Combinations; Gels
PubMed: 37500937
DOI: 10.1007/s00702-023-02656-z -
Turkish Journal of Medical Sciences Feb 2021Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment modality in the management of advanced Parkinson’s disease (PD) despite frequent adverse events and...
BACKGROUND/AIM
Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment modality in the management of advanced Parkinson’s disease (PD) despite frequent adverse events and different rates of dropouts. Efficacy and safety data regarding Turkish patients on LCIG are limited. This study aims to report in detail the efficacy and adverse effect profile of LCIG among advanced PD patients from a Turkish center for movement disorders.
MATERIALS AND METHODS
Twenty-two patients (50% male) who started receiving LCIG between December 2014 and March 2020 were recruited. The efficacy of LCIG was assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS III), Clinical Global İmprovement (CGI) scale, and Quality of Life scale (PDQ8). Improvements in gait disorders and nonmotor features were also questioned. Adverse events (AE) were collated into 3 topics: related to percutaneous endoscopic gastrojejunostomy (PEG-J), device-related, and LCIG infusion-related.
RESULTS
Mean age and pre-LCIG disease duration were 66.7 (8.8) and 13.3 (8.0) years respectively. UPDRS III scores and H-Y scale assessments significantly improved. Better quality of life scores, clinical global improvements, and improvements in dysarthria, dysphagia, and gait were observed. None of our patients dropped out or died during a mean 17.5-month (12.3) period. Overall 20 (90.9%) patients experienced at least one AE. Twelve patients had PEG-J–related complications; three had acute abdomen. Eight (36.4%) patients had device-associated problems. Half of the patients required at least one additional endoscopic procedure and 7 had a device replaced. Mean body weight decreased from 69.5 to 62.5 kg and seven patients had newly onset PNP at a follow-up electromyography. Dyskinesia related to LCIG infusion was observed in 5 (22.7%) patients. There was no significant increase in hallucination among patients.
CONCLUSION
LCIG is an efficient treatment modality in the management of Turkish patients with advanced Parkinson’s disease. Although most of the patients had at least one AE, none of them dropped out. Patient selection, patient compliance, and collaborative management are important steps affecting the success of modality.
Topics: Abdomen, Acute; Aged; Carbidopa; Catheterization; Deglutition Disorders; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Dysarthria; Dyskinesias; Endoscopy; Female; Gait; Gels; Humans; Intestines; Levodopa; Male; Mental Status and Dementia Tests; Middle Aged; Parkinson Disease; Quality of Life; Severity of Illness Index; Treatment Outcome; Turkey
PubMed: 32718129
DOI: 10.3906/sag-2005-96 -
Cells Apr 2022The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa/dopa decarboxylase inhibitor formulations through...
The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa/dopa decarboxylase inhibitor formulations through an increase in levodopa plasma bioavailability. Catechol-O-methyltransferase inhibitors influence the homocysteine metabolism associated with levodopa/dopa decarboxylase application. The objectives of this study were to compare the impact of additional single-day entacapone or opicapone intake on the pharmacokinetic plasma behaviour of levodopa, 3-O-methyldopa and total homocysteine in 15 Parkinson's disease patients, with concomitant scoring of motor symptoms, under standardized conditions. The patients received opicapone plus two doses of 100 mg levodopa/carbidopa and, one week later, two doses of levodopa/carbidopa/entacapone or vice versa. Levodopa, 3-O-methyldopa and total homocysteine were determined with reversed-phase high-performance liquid chromatography. Levodopa bioavailability and its maximum concentration were higher with opicapone. The computed peak-to-trough difference was lower after the second levodopa administration with entacapone. The fluctuation index of levodopa did not differ between both conditions. 3-O-methyldopa decreased on both days. Homocysteine levels did not significantly vary between both conditions. A significant homocysteine decrease occurred with entacapone, but not with opicapone. Motor behaviour improved with entacapone, but not with opicapone. Opicapone baseline scores were significantly better, and thus the potential for the improvement in motor symptoms was lower compared with the entacapone condition. The higher levodopa bioavailability with opicapone suggests that it is more efficacious than entacapone for the amelioration of "off" phenomena in fluctuating patients when co-administered with a levodopa/dopa decarboxylase inhibitor regimen. Both compounds prevented an increase in homocysteine, which is a metabolic marker for an impaired capacity in the performance of methylation processes.
Topics: Antiparkinson Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Carbidopa; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Homocysteine; Humans; Levodopa; Nitriles; Oxadiazoles; Parkinson Disease
PubMed: 35563817
DOI: 10.3390/cells11091511 -
Clinical Pharmacology in Drug... Apr 2023This phase 1 study assessed the safety, tolerability, and pharmacokinetics of a single 24-hour continuous subcutaneous dose of foslevodopa/foscarbidopa in healthy adult...
This phase 1 study assessed the safety, tolerability, and pharmacokinetics of a single 24-hour continuous subcutaneous dose of foslevodopa/foscarbidopa in healthy adult Japanese (N = 24), Han Chinese (N = 8), and White (N = 24) participants. Three doses of foslevodopa/foscarbidopa were evaluated in healthy participants for this study: 480/24, 960/48, and 1440/72 mg/day. Serial blood samples for measurement of levodopa, carbidopa, foslevodopa, foscarbidopa, and 3-O-methyldopa concentrations were collected for 48 hours after foslevodopa/foscarbidopa administration. Safety and tolerability were assessed throughout the study. Point estimates for ratios of central values indicated that the exposure difference between Japanese and White participants was <10%. The maximum concentration and area under the plasma concentration-time curve for both LD and CD following foslevodopa/foscarbidopa continuous subcutaneous infusion were comparable between Han Chinese and White participants. Point estimates for ratios of central values indicated that the exposure difference between Han Chinese and White participants was <14%. The regimens tested were generally well tolerated, and no new safety issues were identified in this study. There were no clinically meaningful differences in LD and CD exposures or pharmacokinetics following administration of foslevodopa/foscarbidopa among White, Japanese, and Han Chinese participants.
Topics: Adult; Humans; Area Under Curve; Dopamine Agonists; Asian People; Carbidopa; White People
PubMed: 36394144
DOI: 10.1002/cpdd.1201 -
Drugs of Today (Barcelona, Spain : 1998) May 2015Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes... (Review)
Review
Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials.
Topics: Amantadine; Antiparkinson Agents; Carbidopa; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease; Practice Guidelines as Topic; Treatment Outcome
PubMed: 26097904
DOI: 10.1358/dot.2015.51.5.2313726 -
The New England Journal of Medicine Jan 2019Levodopa is the main treatment for symptoms of Parkinson's disease. Determining whether levodopa also has a disease-modifying effect could provide guidance as to when in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Levodopa is the main treatment for symptoms of Parkinson's disease. Determining whether levodopa also has a disease-modifying effect could provide guidance as to when in the course of the disease the treatment with this drug should be initiated.
METHODS
In a multicenter, double-blind, placebo-controlled, delayed-start trial, we randomly assigned patients with early Parkinson's disease to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group). The primary outcome was the between-group difference in the mean change from baseline to week 80 in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS; scores range from 0 to 176, with higher scores signifying more severe disease). Secondary analyses included the progression of symptoms, as measured by the UPDRS score, between weeks 4 and 40 and the noninferiority of early initiation of treatment to delayed initiation between weeks 44 and 80, with a noninferiority margin of 0.055 points per week.
RESULTS
A total of 445 patients were randomly assigned: 222 to the early-start group and 223 to the delayed-start group. The mean (±SD) UPDRS score at baseline was 28.1±11.4 points in the early-start group and 29.3±12.1 points in the delayed-start group. The change in UPDRS score from baseline to week 80 was -1.0±13.1 points and -2.0±13.0 points, respectively (difference, 1.0 point; 95% confidence interval [CI], -1.5 to 3.5; P=0.44); this finding of no significant between-group difference at week 80 implies that levodopa had no disease-modifying effect. Between weeks 4 and 40, the rate of progression of symptoms, as measured in UPDRS points per week, was 0.04±0.23 in the early-start group and 0.06±0.34 in the delayed-start group (difference, -0.02; 95% CI, -0.07 to 0.03). The corresponding rates between weeks 44 and 80 were 0.10±0.25 and 0.03±0.28 (difference, 0.07; two-sided 90% CI, 0.03 to 0.10); the difference in the rate of progression between weeks 44 and 80 did not meet the criterion for noninferiority of early receipt of levodopa to delayed receipt. The rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups.
CONCLUSIONS
Among patients with early Parkinson's disease who were evaluated over the course of 80 weeks, treatment with levodopa in combination with carbidopa had no disease-modifying effect. (Funded by the Netherlands Organization for Health Research and Development and others; LEAP Current Controlled Trials number, ISRCTN30518857 .).
Topics: Aged; Antiparkinson Agents; Carbidopa; Disease Progression; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Time-to-Treatment
PubMed: 30673543
DOI: 10.1056/NEJMoa1809983