Objective:

Evaluate the long-term safety, tolerability, and efficacy of foslevodopa/foscarbidopa (LDp/CDp) in people with advanced Parkinson's disease (PD) treated through week 96 of an open-label extension study (OLES).

Background:

LDp/CDp 24-hour/day continuous subcutaneous infusion reduced motor fluctuations and showed a favorable risk/benefit profile in patients with PD in a 52-week(W), open-label, phase 3 study (NCT03781167). Patients who completed the parent study were eligible for this OLES (NCT04379050).

Design/Methods:

The parent study enrolled adults with idiopathic levodopa-responsive PD and inadequately controlled motor fluctuations. The OLES comprised a 96W primary treatment period (PTP) and an optional extended treatment period (ETP). LDp/CDp base infusions were individually optimized between 600–4250 mg LD equivalents/24h. The primary endpoint was safety/tolerability. Secondary endpoints included change in daily normalized "Off" and "On" time and morning akinesia (awakening in the "Off" state). All patients have reached the PTP W96 final visit for this planned interim analysis (data cutoff May 15, 2024). Efficacy data are presented through W96; safety reporting includes the PTP and ETP.

Results:

Of 129 patients in the OLES, 96 (74.4%) completed the 96W PTP; the most common reason for discontinuation was adverse event (AE, n=13[10.3%]). At OLES baseline, the mean(SD) LDp/CDp total daily dose was 1098.3[747.7] mg/day, and at 96W was 2002.9(770.5) mg/day. Treatment-related improvements in "On" and "Off" time and morning akinesia observed during the parent study were generally sustained through the OLES: mean [SD] changes from OLES baseline to W96 (n=81) in "On" time without troublesome dyskinesia (-0.6[3.2] hours, P=.090) and "Off" time (0.7[3.0] hours, P=0.58). At OLES W96, 24.1% of patients reported morning akinesia; 77.7% reported morning akinesia before LDp/CDp initiation in the parent study. Overall, 92.2% of patients experienced ≥1 AE in the OLES.

Conclusions: