Objective: Explore potential reasons for the lower rates of falls with ND0612 vs immediate-release levodopa/carbidopa (IR-LD/CD) therapy reported in the BouNDless study.

Background: Falls are a major cause of morbidity for people with Parkinson’s disease (PwP). We have previously reported that patients treated with an optimized ND0612 treatment regimen had lower rates of falls reported as treatment-emergent adverse events (TEAEs) in the double-blind phase of the BouNDless study (7% vs 12.2% with IR-LD/CD). [1]

Method: BouNDless was an active-controlled trial (NCT04006210) of an optimized ND0612 regimen vs IR-LD/CD in PwP experiencing ≥2.5h daily OFF-time. We explored the effect of ND0612 vs IR-LD/CD on factors previously reported to be associated with falls in PD. Postural instability and gait disorder (PIGD) was assessed by the change from the start of open-label ND0612 conversion to the end of the double-blind phase in the sum of MDS-UPDRS items 2.12 +2.13 +3.10 +3.11 +3.12; functional impact of freezing of gait (FOG) was assessed by MDS-UPDRS item 2.13; cognitive function was assessed by PDQ-39 cognitive domain scores; and impact on dyskinesia was assessed by Hauser diaries and TEAE reporting. Orthostatic hypotension (OH) was assessed via TEAE reporting and blood pressure (BP) assessment.

Results: Treatment with an optimized ND0612 regimen improved overall PIGD scores (improvement of 0.26 vs worsening of 0.02 with IR-LD/CD), reduced the functional impact of FOG (improvement of 0.37 vs worsening of 0.02 with IR-LD/CD), and improved cognition (improvement of 0.90 vs 0.31 with IR-LD/CD). The time spent per day with troublesome dyskinesia decreased from 0.71h to 0.45h with optimized ND0612 therapy and increased from 0.65h to 0.85h with IR-LD/CD; rates of dyskinesia reported as TEAEs were lower in the ND0612 group (2.3% vs 3.8% with IR-LD/CD). The incidence of OH reported as a TEAE with ND0612 was comparable to IR-LD/CD (1.5% vs 1.6%), however drops in BP (systolic BP of ≥20 mm Hg or diastolic BP of ≥10 mm Hg) were observed less frequently in the ND0612 group (24.2% vs. 29.0% with IR-LD/CD).

Conclusion: Taken together, these exploratory findings suggest that treatment with ND0612 has a positive effect on the various factors associated with increased falls in PD and support the observation of reduced falls as a TEAE with optimized ND0612 therapy.

References: [1] Espay AJ, Stocchi F, Pahwa R, et al. Safety and efficacy of continuous subcutaneous levodopa–carbidopa infusion (ND0612) for Parkinson’s disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial. Lancet Neurol; 2024; 23(5):465-476.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reduced-falls-with-nd0612-supportive-analyses-from-the-boundless-phase-3-study/