Effects of Continuous Subcutaneous Infusion of Foslevodopa/Foscarbidopa on Sleep Dysfunction in People with Parkinson's
Robert Hauser1, Bruno Bergmans2, Irene Malaty3, Daniel Cobb4, Jaclyn Homola5, Lars Bergmann5, Resmi Gupta5, Jia Jia5, Megha Shah5, K Ray Chaudhuri6
1University of South Florida, Tampa, FL, USA, 2AZ St-Jan Brugge-Oostende AV, Brugge, Belgium and Ghent University Hospital, Ghent, Belgium, 3University of Florida, Gainesville, FL, USA, 4Neurological Center of North Georgia, LLC, Gainesville, GA, USA, 5AbbVie Inc., North Chicago, IL, USA, 6King's College Hospital, London, UK
Objective:
Assess whether 24-hour/day continuous subcutaneous infusion (CSCI) of foslevodopa/foscarbidopa (LDp/CDp) improves Parkinson’s Disease Sleep Scale-2 (PDSS-2) subdomains in people with Parkinson’s (PwP).
Background:
Sleep is commonly disrupted in PwP. The PDSS-2 provides a Total Score (TS) and subdomain scores for: Motor Symptoms at Night (MS), Parkinson’s Disease Symptoms at Night (PDS), and Disturbed Sleep (DS). A double-blind 12-week phase 3 trial of LDp/CDp CSCI versus levodopa-carbidopa immediate-release (LD/CD-IR) oral tablets (NCT04380142) suggested improvements in the intention-to-treat (ITT) population PDSS-2 TS. An open-label 52-week phase 3 trial of LDp/CDp CSCI (NCT03781167) demonstrated significant improvements in PDSS-2 TS and all subdomains versus baseline in patients completing 52 weeks.
Design/Methods:
Here the 12- and 52-week trials’ ITT PDSS-2 subdomains and TS change from baseline were evaluated post hoc between treatments and within groups. P values are nominal and not corrected for multiplicity.
Results:
Analysis revealed improvements in the 12-week LDp/CDp-treated patients (n=44) MS subdomain (LS mean of difference [SE]: -1.97 [0.54]***), DS subdomain (-2.62 [0.67]***), and TS (-5.40 [1.32]***) versus oral LD/CD-IR (n=59; nominal ***P≤.001). Additionally, within-group improvements versus baseline were seen in the 12-week oral-treated patients for PDS subdomain (mean [SD]: -0.64 [2.20]*) and TS (-1.64 [6.22]*; *P≤.05), in the 12-week LDp/CDp-treated patients subdomains (MS -3.09 [3.18]***, PDS -1.84 [3.32]***, DS -3.41 [4.40]***) and TS (-8.34 [8.86]***), and in the 52-week ITT patients (N=200) subdomains (MS -1.5 [4.77]***, PDS -1.9 [4.44]***, DS -2.4 [4.67]***) and TS (-5.9 [10.85]***; ***P≤.001). Soileau et al. and Aldred et al. previously reported 12- and 52-week LDp/CDp CSCI to be well-tolerated and generally safe.
Conclusions:
These post hoc results demonstrate numerical improvement in two-of-three 12-week trial subdomains and TS in LDp/CDp versus oral (nominal P≤.001), and significant within-group improvements in all three subdomains and TS of the 12- and 52-week LDp/CDp ITT populations, suggesting CSCI of LDp/CDp improves sleep in PwP.