Objective: To investigate the impact of foslevodopa/foscarbidopa (LDp/CDp) on nonmotor symptoms (NMS) in adults with advanced Parkinson’s disease (aPD).

Background: LDp/CDp, a 24-hour per day continuous subcutaneous infusion of levodopa (LD) and carbidopa (CD) prodrugs, has demonstrated a positive risk/benefit motor profile in adults with aPD. However, there is limited data on its impact on NMS.

Method: This post hoc analysis used data on NMS from 2 phase 3 clinical trials of adults with aPD treated with LDp/CDp: a 12-week double-blind double-dummy randomized controlled trial (RCT) of LDp/CDp vs oral LD/CD (NCT04380142) and a 52-week open-label safety trial (OLST) of LDp/CDp (NCT03781167). NMS improvement was measured as a decrease from baseline on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale items of subscale I (MDS-UPDRS-I: Nonmotor Experiences of Daily Living).

Results: In the 12-week RCT, participants in the LDp/CDp group (N = 46) compared with the oral LD/CD group (N = 62) had numerically greater least square (LS) mean (standard deviation [SD]) improvements from baseline on the MDS‑UPDRS‑I single items of pain and other sensations (‑0.67 [0.18] vs ‑0.30 [0.16], P = .066) and urinary problems (‑0.25 [0.15] vs 0.04 [0.14], P = .080); however, they had numerically more constipation (‑0.04 [0.13] vs ‑0.34 [0.12], P = .052) and significantly more hallucinations and psychosis (0.25 [0.10] vs 0.01 [0.09], P = .042). In the 52-week OLST, participants (N = 133) experienced significant improvement from baseline for LS mean (SD) sleep problems (‑0.60 [1.34], P ≤ .001), daytime sleepiness (‑0.20 [1.03], P = .010), pain and other sensations[MK1] (‑0.20 [1.26], P = .048), urinary problems (‑0.30 [1.06], P = .002), and fatigue (‑0.20 [1.21], P = .028). However, cognitive impairment (0.30 [0.92], P ≤ .001) and hallucinations and psychosis (0.40 [0.91], P ≤ .001) increased significantly.

Conclusion: These preliminary data suggest possible beneficial effects of LDp/CDp on certain NMS—such as sleep, daytime sleepiness, urinary symptoms, and pain, perhaps with longer-term use. The item for hallucinations and psychosis increased in the setting of the studies, where the possibility to adjust nighttime dosing was limited (OLST) or not available (RCT). This indicates further research is warranted and may support refined patient selection.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-foslevodopa-foscarbidopa-treatment-on-nonmotor-symptom-burden-in-advanced-parkinsons-disease/