Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study

Jason Aldred; Eric Freire-Alvarez; Alexander V Amelin; Angelo Antonini; Bruno Bergmans; Filip Bergquist; Manon Bouchard; Kumar Budur; Camille Carroll; K Ray Chaudhuri; Susan R Criswell; Erik H Danielsen; Florin Gandor; Jia Jia; Thomas E Kimber; Hideki Mochizuki; Weining Z Robieson; Amy M Spiegel; David G Standaert; Saritha Talapala; Maurizio F Facheris; Victor S C Fung

doi:10.1007/s40120-023-00533-1

Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study

Neurol Ther. 2023 Dec;12(6):1937-1958. doi: 10.1007/s40120-023-00533-1. Epub 2023 Aug 26.

Authors

Jason Aldred¹, Eric Freire-Alvarez², Alexander V Amelin³, Angelo Antonini⁴, Bruno Bergmans^{5

6}, Filip Bergquist⁷, Manon Bouchard⁸, Kumar Budur⁹, Camille Carroll¹⁰, K Ray Chaudhuri^{11

12}, Susan R Criswell¹³, Erik H Danielsen¹⁴, Florin Gandor^{15

16}, Jia Jia⁹, Thomas E Kimber^{17

18}, Hideki Mochizuki¹⁹, Weining Z Robieson⁹, Amy M Spiegel⁹, David G Standaert²⁰, Saritha Talapala⁹, Maurizio F Facheris⁹, Victor S C Fung^{21

22}

Affiliations

¹ Selkirk Neurology and Inland Northwest Research, 610 S Sherman St, Spokane, WA, 99202, USA. JAldred@selkirkneurology.com.
² Neurology Department, University General Hospital of Elche, Carrer Almazara, 11, 03203, Elche, Spain.
³ Department of Neurology and Neurosurgery, Pavlov First Saint Petersburg State Medical University, Ulitsa L'va Tolstogo, 6-8, St. Petersburg, 197022, Russia.
⁴ Parkinson and Movement Disorders Unit, Department of Neuroscience, Padua University, Via VIII Febbraio, 2, 35122, Padua, Italy.
⁵ Department of Neurology, AZ St-Jan Brugge-Oostende AV, Ruddershove 10, 8000, Brugge, Belgium.
⁶ Department of Neurology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.
⁷ Department of Pharmacology, University of Gothenburg, Universitetsplatsen 1, 405 30, Gothenburg, Sweden.
⁸ Clinique Neuro-Lévis, 1190 A Rue de Courchevel #301, Lévis, QC, G6W 0M5, Canada.
⁹ AbbVie Inc., 1 N. Waukegan Road, North Chicago, IL, 60064, USA.
¹⁰ Faculty of Health, University of Plymouth, Drake Circus, Plymouth, PL4 8AA, UK.
¹¹ Parkinson's Foundation International Centre of Excellence, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
¹² King's College Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK.
¹³ Department of Neurology, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, 63130, USA.
¹⁴ Department of Neurology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.
¹⁵ Movement Disorders Hospital, Straße Nach Fichtenwalde 16, 14547, Beelitz-Heilstätten, Germany.
¹⁶ Department of Neurology, Otto-Von-Guericke University Magdeburg, Universitätspl. 2, 39106, Magdeburg, Germany.
¹⁷ Department of Neurology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000, Australia.
¹⁸ Department of Medicine, University of Adelaide, 4 North Terrace, Adelaide, SA, 5000, Australia.
¹⁹ Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
²⁰ Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, 1670 University Blvd, Birmingham, AL, 35233, USA.
²¹ Movement Disorders Unit, Westmead Hospital, Cnr Hawkesbury Road and Darcy Rd, Westmead, NSW, 2145, Australia.
²² Faculty of Medicine and Health, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.

Abstract

Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD.

Methods: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700-4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale-2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L).

Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, "On" time without troublesome dyskinesia and "Off" time were improved from baseline (mean [standard deviation (SD)] change in normalized "On" time without troublesome dyskinesia, 3.8 [3.3] hours; normalized "Off" time, -3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved.

Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD.

Trial registration number: ClinicalTrials.gov identifier NCT03781167.

Keywords: Advanced Parkinson’s disease; Foslevodopa/foscarbidopa; Levodopa/carbidopa prodrugs; Motor fluctuations; Subcutaneous infusion.

Associated data

ClinicalTrials.gov/NCT03781167