A Novel Levodopa/Carbidopa Prodrug (ABBV-951) 24-Hour Continuous Subcutaneous Infusion Treatment for Parkinson’s Disease (P3.8-037)

Objective: Characterize the levodopa pharmacokinetics (PK) and safety/tolerability of ABBV-951 in a first-in-human study following continuous subcutaneous (SC) infusion. Background: Parkinson’s disease is the second most common neurodegenerative disease and is characterized by progressive degeneration of the dopaminergic system resulting in bradykinesia, rigidity, tremor and postural instability. Early stage symptoms are managed with oral treatment; however, as Parkinson’s disease progresses, symptoms are no longer well controlled by oral medication due to the short half-life of levodopa and a narrowing therapeutic window. Duopa (levodopa-carbidopa intestinal gel) can overcome the short half-life of levodopa and offer superior efficacy compared to oral levodopa/carbidopa; however, this delivery requires percutaneous endoscopic gastrostomy (PEG) tube placement . ABBV-951 is a novel levodopa/carbidopa prodrug which has the potential to be delivered through a minimally invasive SC infusion and provide therapeutic levels of levodopa. Design/Methods: ABBV-951 was administered SC to the abdomen to 6 healthy older (45–75 years old) volunteers over a 72 hour period. Serial plasma PK samples were collected to assay for levodopa concentrations. Safety and tolerability were assessed throughout the study. Results: Following ABBV-951 administration, levodopa mean PK profile over initial 16 hours is similar to previous Duopa phase 1 study in Parkinson’s disease patients. ABBV-951 still maintains stable levodopa exposures for the rest treatment period. Steady state levodopa exposure was achieved at 2 hours indicating rapid conversion of the prodrug to levodopa. Four/six subjects reported mild infusion site pain ≤30 minutes after infusion initiation with no reports of pain after. Following the initiation of infusion one subject had an adverse event of edema at the infusion site. Conclusions: ABBV-951 was able to provide stable levodopa exposures over 72 hours via a less invasive SC route of delivery. Disclosure: Dr. Rosebraugh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie. Dr. Rosebraugh holds stock and/or stock options in AbbVie. Dr. Kym has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie. Dr. Kym holds stock and/or stock options in AbbVie. Dr. Liu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie. Dr. Liu holds stock and/or stock options in AbbVie. 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. Benesh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie Inc. Dr. Benesh holds stock and/or stock options in AbbVie Inc.