Category: Parkinson’s Disease: Clinical Trials
Objective: To evaluate time to ON without troublesome dyskinesia (‘good ON’) and patterns of motor-state stability throughout the day in patients with advanced Parkinson’s disease (aPD) treated with foslevodopa/foscarbidopa (LDP/CDP) vs oral levodopa/carbidopa (LD/CD).
Background: The goal of 24-hr subcutaneous infusion of LDP/CDP is to enable continuous dopaminergic stimulation and stable plasma LD concentrations. Temporal patterns of motor-symptom improvements throughout the day have not been established for LDP/CDP.
Method: Diary data collecting motor-states (OFF, good ON, ON with troublesome dyskinesia, asleep) at 30-min intervals over 3 days (normalized to 16-hr waking days) were collected from a 12-week (W), controlled Phase 3 trial of LDP/CDP vs LD/CD in aPD patients (NCT04380142). In post-hoc analysis, adjusted linear regression models assessed changes at W12 relative to baseline and between treatment groups for time to good ON after waking, and for motor states throughout the day at 30-min and 4-hr intervals, as well as average number of daily motor fluctuations, a proxy for motor-state stability.
Results: Complete baseline and W12 diary data were available for 46 LDP/CDP and 60 LD/CD patients. At W12, LDP/CDP patients reached good ON faster (means: 28.9 vs 82.9 min; p=0.004) and nearly twice as frequently within 30 min after waking (84.7% vs 47.6%; p<0.001) vs LD/CD. OFF was reduced throughout the day for LDP/CDP patients with only 13.8% (vs 57.8%; p<0.001) reporting OFF within 30 min after waking vs LD/CD. Analysis of 4-hr intervals showed LDP/CDP patients had significant increases in good ON and reductions in OFF at W12 relative to baseline, which was sustained through the day (Fig 1 and 2). Although the number of daily motor fluctuations was comparable at baseline (means: 12.6 vs 11.1; p=0.178), at study end, LDP/CDP patients reported significantly fewer daily fluctuations (means: 4.7 vs 7.2; p<0.001) with 64.5% reporting ≤6 fluctuations/day vs 38.6% in LD/CD (Fig 3).
Conclusion: Patients on LDP/CDP more commonly reported good ON after awakening and had greater stability of their good ON time throughout the day, with fewer motor fluctuations compared to LD/CD patients. Consistent motor-symptom control and reduced fluctuations demonstrate the stability offered by LDP/CDP over the day.
To cite this abstract in AMA style:
R. Pahwa, M. Soileau, D. Standaert, V. Fung, T. Kimber, I. Malaty, A. Merola, A. Epstein, C. Yan, A. Alobaidi, A. Shewale, N. Fisseha, A. Jeong, M. Facheris, P. Kukreja, J. Zamudio, J. Aldred. Rapid onset of good ON time and improvement in motor-state stability in aPD patients after treatment with continuous subcutaneous foslevodopa/foscarbidopa [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/rapid-onset-of-good-on-time-and-improvement-in-motor-state-stability-in-apd-patients-after-treatment-with-continuous-subcutaneous-foslevodopa-foscarbidopa/. Accessed June 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/rapid-onset-of-good-on-time-and-improvement-in-motor-state-stability-in-apd-patients-after-treatment-with-continuous-subcutaneous-foslevodopa-foscarbidopa/