Post hoc exploratory analysis of the effect of foslevodopa/foscarbidopa continuous subcutaneous infusion on nocturia in patients with Parkinson’s disease

Introduction

Parkinson’s disease (PD) non-motor symptom burden, including nocturia and sleep disturbances, worsens with disease progression. Continuous dopaminergic drug delivery with nocturnal infusion in PD demonstrated improvements in sleep and nocturia. Foslevodopa/foscarbidopa (LDp/CDp) provides 24-hour continuous drug delivery of levodopa/carbidopa (LD/CD) prodrugs via continuous subcutaneous infusion (CSCI).

Methods

Least-squares mean nocturia changes (measured via Parkinson’s Disease Sleep Scale-2 item 8) in patients with PD from a randomized 12-week phase 3 trial of LDp/CDp CSCI versus oral LD/CD (NCT04380142) and a 52-week open-label LDp/CDp CSCI phase 3 trial (NCT03781167) were analyzed post hoc via mixed-effects regression and analysis of covariance. Correlation coefficients at baseline (BL) and in change from BL to week 12 or week 52 (Δ BL-wk 12 or Δ BL-wk 52) for nocturia and quality of life (QoL, measured as Parkinson’s Disease Questionnaire [PDQ-39] Summary Index score) were calculated via Spearman’s test.

Results

This exploratory analysis demonstrated significant and sustained improvement in nocturia symptoms from BL with LDp/CDp treatment in both the randomized (to week 12; n = 44; nominal p ≤ 0.01) and open-label (to weeks 6, 13, 26, and 52; with n = 176, 149, 107, and 75, respectively; nominal p ≤ 0.001 for all) trials. Nocturia improvement was significantly greater in LDp/CDp- versus oral-treated patients (n = 59; nominal p ≤ 0.05). A significant positive correlation between nocturia and QoL was shown at BL and between Δ BL-wk 12 in the randomized trial (nominal p ≤ 0.05 for both), while open-label results showed no significant correlations.

Conclusions

LDp/CDp-treated patients with PD demonstrated significantly improved nocturia with 24-hour therapy, 12-week nocturia improvements were significantly greater than oral therapy, and patient-reported nocturia may correlate with QoL.