Abstract Details

Title Safety of Foslevodopa/Foscarbidopa During Optimization and Maintenance Treatment: Post Hoc Analysis of a Phase 3 Trial

Topic Movement Disorders

Presentation(s) S32 - Movement Disorders: Trials (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Background Continuous subcutaneous infusion with foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs, provides individualized, 24-hour/day therapy.

Objective To characterize the time course of adverse events (AEs) in patients with Parkinson’s disease (PD) and motor fluctuation treated with foslevodopa/foscarbidopa.

Design/Methods Patients aged ≥30 years with idiopathic, LD-responsive PD inadequately controlled with current therapy (≥2.5 average “Off” hours/day) were enrolled in a 12-week, phase 3, randomized, double-blind study comparing foslevodopa/foscarbidopa to oral immediate release LD/CD (NCT04380142). Foslevodopa/foscarbidopa doses were titrated and individualized during the 4-week optimization period, followed by a stable dose regimen during the 8-week maintenance period. Safety was assessed in all patients who received ≥1 dose of study drug.

Results A total of 74 patients received foslevodopa/foscarbidopa. Overall AEs occurred more frequently during the 4-week optimization vs the 8-week maintenance period (74.3% vs 67.9%), as did treatment discontinuations due to AEs (16.2% vs 7.1%). A greater proportion of patients experienced movement-related AEs during optimization vs maintenance, including dyskinesia (10.8% vs 0%), “On” and “Off” phenomenon (6.8% vs 1.8%), and falls (13.5% vs 8.9%). Incidence of infusion site AEs was higher during optimization vs maintenance (67.6% vs 58.9%); individual infusion site AEs generally followed a similar trend (erythema [20.3% vs 21.4%], pain [21.6% vs 8.9%], cellulitis [10.8% vs 12.5%], bruising [6.8% vs 1.8%], nodules [5.4% vs 3.6%]).

Conclusions In this phase 3 trial involving patients with PD treated with foslevodopa/foscarbidopa, AEs and discontinuations were generally higher during the 4-week optimization compared with the 8-week maintenance period. Higher rates of AEs and discontinuations during optimization may have been the result of the dose titration process and acclimation to a new drug delivery system. Patient and physician training, education, and expectation setting before treatment initiation and during optimization may help reduce rates of treatment discontinuation.

Authors/Disclosures
Drew S. Kern, MD, FAAN (University of Colorado) PRESENTER	Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. The institution of Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. The institution of Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. The institution of Dr. Kern has received research support from Boston Scientific. The institution of Dr. Kern has received research support from AbbVie Pharmaceticals. Dr. Kern has received research support from Medtronic.
Khashayar Dashtipour, MD, PhD	Dr. Dashtipour has nothing to disclose.
Jason L. Aldred, MD, FAAN (Selkirk Neurology)	Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medtronic. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Boston Scientific. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Abbvie. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan . Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quadralynx. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Abbvie. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Adamas. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Allergan. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Boston Scientific. Dr. Aldred has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for TEVA. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Medtronic. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for US World Meds. Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion. Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amneal. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Aldred has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Arete Neuroscience, PLLC. The institution of Dr. Aldred has received research support from Biogen . The institution of Dr. Aldred has received research support from Abbvie. The institution of Dr. Aldred has received research support from Atara. The institution of Dr. Aldred has received research support from Takeda. The institution of Dr. Aldred has received research support from Merz. The institution of Dr. Aldred has received research support from AstraZeneca. The institution of Dr. Aldred has received research support from Neurocrine. The institution of Dr. Aldred has received research support from Aptinyx. The institution of Dr. Aldred has received research support from Cerevance. The institution of Dr. Aldred has received research support from Boston Scientific . The institution of Dr. Aldred has received research support from Parkinson Foundation . The institution of Dr. Aldred has received research support from Roche. The institution of Dr. Aldred has received research support from Theravance. The institution of Dr. Aldred has received research support from Triplet Therapeutics. The institution of Dr. Aldred has received research support from UCB. The institution of Dr. Aldred has received research support from Cerevel . The institution of Dr. Aldred has received research support from Sage Therapeutics. The institution of Dr. Aldred has received research support from Annovis. The institution of Dr. Aldred has received research support from Biovie. The institution of Dr. Aldred has received research support from Athira. The institution of Dr. Aldred has received research support from IRL. The institution of Dr. Aldred has received research support from NeuroDerm.
Thomas E. Kimber, PhD, FRACP (Royal Adelaide Hospital)	Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Seqiris. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Kimber has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Pfizer.
	No disclosure on file
Pavnit Kukreja, PharmD (AbbVie)	Dr. Kukreja has received personal compensation for serving as an employee of AbbVie. Dr. Kukreja has stock in AbbVie.
Lars Bergmann	Lars Bergmann has received personal compensation for serving as an employee of Abbvie. Lars Bergmann has stock in Abbvie.
Nahome Fisseha	Nahome Fisseha has received personal compensation for serving as an employee of AbbVie. Nahome Fisseha has received stock or an ownership interest from AbbVie.
Resmi Gupta (Abbvie Inc)	No disclosure on file
	No disclosure on file
Anna Jeong, MD (AbbVie)	Dr. Jeong has received personal compensation for serving as an employee of AbbVie. An immediate family member of Dr. Jeong has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Stryker. Dr. Jeong has stock in AbbVie.
Victor Fung, MD, MBBS, PhD	Dr. Fung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Fung has received publishing royalties from a publication relating to health care.
	No disclosure on file