Category: Parkinson’s Disease: Clinical Trials
Objective: This analysis aims to study the evolution of OFF and ON patterns during a 12-hour daily period in patients with Parkinson’s disease (PD) and motor fluctuations (MF) following the administration of each levodopa (LD)/carbidopa (CD) intake.
Background: Optimising LD treatment regimens through catechol-O-methyltransferase (COMT) inhibition is an effective strategy in the management of MF in patients with PD. Study 203 demonstrated that adding the COMT inhibitor opicapone (OPC) to LD/CD therapy increases LD systemic exposure and decreases OFF-time in patients with PD and MF. This post-hoc analysis evaluated the OFF/ON patterns in patients included in Study 203 treated with LD/CD therapy, before OPC was added.
Method: Study 203 was an exploratory, open-label, modified cross-over trial. All participants received LD/CD 500/125 mg, administered as 5 daily intakes of 100/25 mg every 3 hours for 2 weeks and were then randomly (1:1) assigned to LD/CD 400/100 mg given in 4 or 5 daily intakes plus OPC 50 mg for 2 additional weeks. LD 12-hour pharmacokinetics (PK) was the primary outcome, with the last daily intake being excluded from the PK analysis; 12-hour patient ON/OFF monitoring was a key secondary outcome. This study evaluated ON/OFF patterns in patients treated with the LD/CD 500/125 mg regimen before randomisation.
Results: Overall, 24 patients were recruited and received the LD/CD 500/125 mg regimen [table1]. For all daily intakes, the mean total ON-time was 5h 49mins and the mean total OFF-time was 6h 15mins [figure1]. The total OFF-time was divided into time-to-ON (2h 52mins) and ‘wearing-off’ (3h 23mins), which represented 45.9% and 54.1% of the total OFF-time, respectively.
Conclusion: The current analysis suggests that in LD-treated patients with ‘wearing-off’ MF time-to-ON following a dose of LD is responsible for nearly half of total daily OFF-time.
Supported by Bial.
To cite this abstract in AMA style:
J. Ferreira, W. Poewe, O. Rascol, F. Stocchi, A. Antonini, J. Moreira, B. Guimarães, J-F. Rocha. Characterisation of OFF-Time in Levodopa-Treated Parkinson’s Patients: A Post-hoc Analysis of an Exploratory Trial [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/characterisation-of-off-time-in-levodopa-treated-parkinsons-patients-a-post-hoc-analysis-of-an-exploratory-trial/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/characterisation-of-off-time-in-levodopa-treated-parkinsons-patients-a-post-hoc-analysis-of-an-exploratory-trial/