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Introduction <p>We evaluated continuous subcutaneously administered foslevodopa/foscarbidopa (LDp/CDp) in younger patients earlier within advanced Parkinson’s disease (aPD).</p> Methods <p>This phase&#xa0;3 trial included patients aged ≥ 30&#xa0;years with levodopa-responsive PD, Mini-Mental State Examination score ≥ 24, and levodopa equivalent dose ≥ 400&#xa0;mg/day.&#xa0;Patients were considered by the investigator as inadequately controlled on current oral/transdermal therapy and experienced ≥ 2.5&#xa0;h/day “Off” time, with recognizable “On”/“Off” states. Patients were randomized (1:1) to LDp/CDp plus placebo capsules or orally administered immediate-release levodopa/carbidopa plus placebo infusion.&#xa0;This post&#xa0;hoc exploratory analysis focused on younger patients (≤ 65&#xa0;years) earlier within aPD (Hoehn and Yahr stage ≤ 2 [“On” state], ≤ 5&#xa0;years since motor fluctuations started). Outcomes included change from baseline (CFB) to week&#xa0;12 in “Off” and “On” time, Movement Disorder Society&#xa0;Unified PD Rating Scale (MDS-UPDRS) II, 39-item PD Questionnaire (PDQ-39), and PD Sleep Scale-2 (PDSS-2).</p> Results <p>Twenty-six patients met subgroup criteria (LDp/CDp, <i>n</i> = 13; orally administered levodopa/carbidopa, <i>n</i> = 13). Despite small sample sizes, at week&#xa0;12, LDp/CDp was associated with significantly greater improvements in “Off” time (mean [SD] CFB − 3.7 [3.1] vs − 1.6 [2.9]&#xa0;h; <i>P</i> = 0.0011), “On” time without troublesome dyskinesia (+ 3.9 [3.3] vs + 1.4 [3.8]&#xa0;h; <i>P</i> = 0.0011), and PDSS-2 (− 6.4 [4.6] vs − 1.8 [3.1]; <i>P</i> = 0.0220) vs orally administered levodopa/carbidopa. Mean (SD) CFB to week&#xa0;12 (LDp/CDp vs orally administered levodopa/carbidopa) was + 4.2 (2.8) vs + 1.9 (4.6)&#xa0;h for “On” time without dyskinesia (<i>P</i> = 0.0878), − 3.0 (6.4) vs − 0.9 (3.5) for MDS-UPDRS&#xa0;II (<i>P</i> = 0.3539), and − 9.9 (7.4) vs − 1.9 (9.4) for PDQ-39 (<i>P</i> = 0.0534). For most assessments, treatment differences were numerically larger in the subgroup vs the overall population. Safety findings were consistent with the overall population.</p> Conclusions <p>LDp/CDp was associated with significantly greater improvements in motor function and sleep vs orally administered levodopa/carbidopa in younger patients earlier within aPD whose symptoms were inadequately controlled by oral/transdermal therapies. Larger real-world studies are needed to confirm findings.</p> Trial Registration <p>ClinicalTrials.gov identifier, NCT04380142.</p>

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Foslevodopa/Foscarbidopa in Younger Patients Earlier Within Advanced Parkinson’s Disease: Post Hoc Analysis of a Randomized Trial

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  • 发表日期：

    2025年12月1日

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  • Angelo Antonini,
  • Bruno Bergmans,
  • Drew S. Kern,
  • Florin Gandor,
  • Noriko Nishikawa,
  • David G. Standaert,
  • Bjoern Fritz,
  • Resmi Gupta,
  • Toshiki Nozaki,
  • Megha B. Shah,
  • Lars Bergmann,
  • Thomas Kimber

摘要

Introduction

We evaluated continuous subcutaneously administered foslevodopa/foscarbidopa (LDp/CDp) in younger patients earlier within advanced Parkinson’s disease (aPD).

Methods

This phase 3 trial included patients aged ≥ 30 years with levodopa-responsive PD, Mini-Mental State Examination score ≥ 24, and levodopa equivalent dose ≥ 400 mg/day. Patients were considered by the investigator as inadequately controlled on current oral/transdermal therapy and experienced ≥ 2.5 h/day “Off” time, with recognizable “On”/“Off” states. Patients were randomized (1:1) to LDp/CDp plus placebo capsules or orally administered immediate-release levodopa/carbidopa plus placebo infusion. This post hoc exploratory analysis focused on younger patients (≤ 65 years) earlier within aPD (Hoehn and Yahr stage ≤ 2 [“On” state], ≤ 5 years since motor fluctuations started). Outcomes included change from baseline (CFB) to week 12 in “Off” and “On” time, Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) II, 39-item PD Questionnaire (PDQ-39), and PD Sleep Scale-2 (PDSS-2).

Results

Twenty-six patients met subgroup criteria (LDp/CDp, n = 13; orally administered levodopa/carbidopa, n = 13). Despite small sample sizes, at week 12, LDp/CDp was associated with significantly greater improvements in “Off” time (mean [SD] CFB − 3.7 [3.1] vs − 1.6 [2.9] h; P = 0.0011), “On” time without troublesome dyskinesia (+ 3.9 [3.3] vs + 1.4 [3.8] h; P = 0.0011), and PDSS-2 (− 6.4 [4.6] vs − 1.8 [3.1]; P = 0.0220) vs orally administered levodopa/carbidopa. Mean (SD) CFB to week 12 (LDp/CDp vs orally administered levodopa/carbidopa) was + 4.2 (2.8) vs + 1.9 (4.6) h for “On” time without dyskinesia (P = 0.0878), − 3.0 (6.4) vs − 0.9 (3.5) for MDS-UPDRS II (P = 0.3539), and − 9.9 (7.4) vs − 1.9 (9.4) for PDQ-39 (P = 0.0534). For most assessments, treatment differences were numerically larger in the subgroup vs the overall population. Safety findings were consistent with the overall population.

Conclusions

LDp/CDp was associated with significantly greater improvements in motor function and sleep vs orally administered levodopa/carbidopa in younger patients earlier within aPD whose symptoms were inadequately controlled by oral/transdermal therapies. Larger real-world studies are needed to confirm findings.

Trial Registration

ClinicalTrials.gov identifier, NCT04380142.