Safety and Tolerability During a 4-Week Continuous Subcutaneous Infusion of ABBV-951, a New Drug Formulation for the Treatment of Parkinson's Disease: Final Results of a Phase 1b Study

Objective: Evaluate safety/tolerability of ABBV-951 delivered via continuous subcutaneous infusion(CSCI) in Parkinson’s disease(PD) patients. Background: ABBV-951 is a new soluble formulation of carbidopa and levodopa prodrugs, delivered as a CSCI via an external pump, being developed for the treatment of PD. Previous Ph1 studies demonstrated that ABBV-951 was well-tolerated in healthy volunteers. Here we assessed the safety of individually titrated therapeutic doses of ABBV-951 administered to PD patients via 24-hour CSCI for 28 days in an outpatient setting. Design/Methods: Eligible subjects for this Ph1b study(NCT03374917) were PD patients whose motor complications were inadequately controlled by oral medications and who experienced a minimum of 2.5h/day “Off” time. A screening and titration period were followed by weekly study visits. Local and systemic safety/tolerability were assessed by the infusion site assessment 2-part rating scale(numeric scores:0–7 and letter grades:A–G) and adverse event(AE) monitoring. Exploratory efficacy assessed by mean change from baseline in MDS-UPDRS scores and PD Diaries. Results: Twenty-one patients were included in the safety analysis(62% male, mean age 61.6, 43% with ≥10 years PD duration). AEs occurred in 19 patients(90.5%); 2 serious AEs (cellulitis and abdominal abscess) were reported in 1 patient who prematurely discontinued the study. Another patient prematurely discontinued due to an AE of infusion site infection. Five patients(24%) had Numeric Score ≥3 or Letter Grade ≥C on the Infusion Site Evaluation Scale; all other patients were classified as 0, 1, or 2 score or A or B grade, consistent with findings reported for other CSCI therapies. There were no clinically significant changes in laboratory, ECG, or vital sign parameters. ABBV-951 doses ranged 400mg-3400mg levodopa equivalents. Exploratory efficacy results showed decreased “Off” time compared to baseline. Conclusions: Results demonstrate that ABBV-951 was well-tolerated when delivered via 24-hour CSCI for 28 days and support future investigations of ABBV-951 as a potentially new treatment option for PD patients. Disclosure: Dr. Facheris has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie. Dr. Facheris holds stock and/or stock options in AbbVie. Dr. Criswell has nothing to disclose. Dr. Pavasia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia, Acorda, Adamas, Impax/Amneal, Lundbeck, and US world meds. Dr. Pahwa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received consulting fees from Abbott, Abbvie, ACADIA, Acorda, Adamas, Cala Health, Global Kinetics, Lundbeck, Neurocrine, PhotoPharmics, Prilenia, Sunovion, Teva Neuroscience, US World Meds, Biogen, Boston Scientific, Cavion, Intec, Jazz, Kyowa, Lilly. Dr. Pahwa has received research support from has received research grants from Abbvie, Adamas, Avid, Biotie, Boston Scientific, Civitas, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group. Dr. Locke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie Inc.. Dr. Locke holds stock and/or stock options in AbbVie Inc.. Dr. Robieson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie Inc.. Dr. Robieson holds stock and/or stock options in AbbVie Inc.. Dr. Shprecher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia, Acorda, Lundbeck, Neurocrine, Sunovion, US World Meds. Dr. Shprecher has received research support from Abbvie, Acadia, Acorda, Arizona Alzheimer’s Consortium, Biogen, Eli Lilly, Enterin, Esai, Neurocrine, NIH, MJFF, and Teva/Nuvelution.