Improvement in Motor Consistency and Stability with Foslevodopa/Foscarbidopa in Advanced Parkinson’s Disease: Post Hoc Analysis of Two Phase 3 Clinical Trials

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INTRODUCTION: People with advanced Parkinson's disease (aPD) frequently experience unpredictable "Off" time and debilitating motor fluctuations. Foslevodopa/foscarbidopa (LDp/CDp), a levodopa/carbidopa (LD/CD) prodrug, is delivered as a 24-h continuous subcutaneous infusion. This post hoc analysis evaluated the efficacy of LDp/CDp in achieving consistent motor symptom control and stable motor states in people with aPD. METHODS: Diaries of people with aPD treated with LDp/CDp participating in a 12-week, phase 3, randomized controlled trial (RCT) were evaluated versus oral LD/CD, and in a 52-week open-label, single-arm trial (OLT) with LDp/CDp alone. Motor symptom control was assessed by frequency (30-min intervals) and duration (4-h blocks) of motor states (good "On" time [without dyskinesia or troublesome dyskinesia] or "Off" time) over a 16-h waking day. Motor state stability was evaluated by changes in daily motor fluctuations and extreme fluctuations (defined as transition from "Off" to "On" with troublesome dyskinesia, or vice versa). Outcomes were analyzed using adjusted regression models. RESULTS: Analysis included 47 (RCT) and 55 (OLT) people with aPD on LDp/CDp. In the RCT, LDp/CDp had an approximately 1-h gain in good "On" time in the mornings versus a quarter-hour gain for those on LD/CD (P = 0.001), with > 80% of participants on LDp/CDp waking up in good "On." At week 12, fewer motor fluctuations/day occurred with LDp/CDp versus LD/CD (3.2 vs 5.3; nominal P = 0.001), and twice as many participants on LDp/CDp had ≤ 3 fluctuations/day (53.2% vs 25.8%). In the OLT, the results seen at 12 weeks were sustained through week 52, with fewer mean fluctuations/day (3.1) than baseline (7.4) and more participants reporting ≤ 3 fluctuations/day at 52 weeks (66.6%) versus baseline (12.9%). CONCLUSION: LDp/CDp provided consistent motor symptom control throughout the day, enhanced motor state stability, and reduced motor fluctuation, highlighting LDp/CDp's potential to significantly improve the management of unpredictable motor states and overall quality of life for people with aPD. TRIAL INFORMATION: Clinicaltrials.gov ID: NCT04380142, NCT03781167.

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