Dataset Information

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

ABSTRACT:

Introduction

A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and patterns of motor-symptom control throughout the waking day were compared between CLES and IR-CL.

Methods

Post hoc analyses of APD patient-diary data from the phase 3 randomized controlled trial were used to compare changes in time to ON-woTD after waking, motor-symptom control throughout the waking day, occurrence of extreme fluctuations between OFF and "on" with troublesome dyskinesia, and motor-state transitions with CLES versus IR-CL from baseline to week 12.

Results

The sample included 33 CLES-treated and 30 IR-CL-treated patients. Among the CLES group, the percentage of patient days achieving ON-woTD within 30 min of waking was three times higher at week 12 versus baseline (33% vs. 11%, p = 0.0043); no significant change occurred with IR-CL. When the waking day was divided into four 4-h periods, CLES versus IR-CL treatment produced significantly greater reductions in OFF during three periods, and two periods had increased ON-woTD. Fewer CLES-treated patients had extreme fluctuations at week 12 (3% vs. 23%, p = 0.0224) compared to IR-CL-treated patients. From baseline to week 12, CLES-treated patients had greater reductions in the average number of motor-state transitions compared to IR-CL-treated patients (- 1.6, p = 0.0295).

Conclusion

CLES-treated patients experienced a more rapid onset of ON-woTD after waking and greater consistency of ON-woTD throughout their waking day than IR-CL-treated patients.

SUBMITTER: Pahwa R

PROVIDER: S-EPMC9095782 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

Pahwa Rajesh R Aldred Jason J Gupta Niodita N Terasawa Emi E Garcia-Horton Viviana V Steffen David R DR Kandukuri Prasanna L PL Chaudhari Vivek S VS Jalundhwala Yash J YJ Bao Yanjun Y Kukreja Pavnit P Isaacson Stuart H SH

Neurology and therapy 20220222 2

<h4>Introduction</h4>A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and ...[more]

PMID: 35192177

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Project description:BackgroundLevodopa-induced motor complications are a significant concern in the treatment of Parkinson's disease (PD). Dopamine decarboxylase inhibitors (DCIs) such as benserazide (BSZ) and carbidopa (CD) are commonly used in conjunction with levodopa to manage PD symptoms. However, their association with motor complications remains unclear.MethodsWe performed a retrospective pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) data from Q1 2004 to Q2 2024. The study included only adverse event reports (AERs) related to oral administration of drugs indicated for PD. We concentrated on motor complications, selecting two system organ classes (SOCs) associated with motor fluctuations and dyskinesia: nervous system disorders and general disorders/administration site conditions. Disproportionality analysis and Bayesian methods were utilized to identify and assess motor complication signals associated with BSZ and CD. A signal was deemed significant if it met the following criteria: reporting odds ratio (ROR) ≥ 3 with a 95% confidence interval (CI) lower bound >1, information component (IC) 95% CI lower bound >0, and empirical Bayes geometric mean (EBGM) 95% CI lower bound >2.ResultsThe analysis identified 8,744 AERs related to motor complications, recording 19,482 adverse events (AEs). The study highlighted motor complications such as dyskinesia, the on-off phenomenon, freezing episodes, and wearing-off, linked to the oral use of both BSZ and CD. Dyskinesia showed high RORs for both BSZ (16.5, 95% CI 14.76-18.45) and CD (13.81, 95% CI 13.02-14.65). The on-off phenomenon demonstrated a more pronounced ROR for BSZ at 170.74 (95% CI 145.03-201.01) compared to CD at 67.5 (95% CI 59.46-76.63). Wearing-off was notably higher for CD, with an ROR of 7.66 (95% CI 7.08-8.28), compared to BSZ's ROR of 3.03 (95% CI 2.37-3.88).ConclusionThe findings indicate that the choice of DCI affects the risk profile of motor complications in PD. BSZ is associated with increased risks of dyskinesia and the on-off phenomenon, whereas CD is linked to a higher risk of wearing-off. Future research should explore the mechanisms underlying these differences to guide the selection of the most appropriate DCI for individual patients.

Dataset Information

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

Introduction

Methods

Results

Conclusion

Publications

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

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