Foslevodopa/Foscarbidopa Is Well Tolerated and Maintains Stable Levodopa and Carbidopa Exposure Following Subcutaneous Infusion

Abstract

Background: Foslevodopa/foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson’s disease (aPD). Objective: The current work characterizes the levodopa (LD) and carbidopa (CD) pharmacokinetics (PK) following SC infusions of foslevodopa/foscarbidopa delivered at four different infusion rates in PD patients. Methods: This was a Phase 1, single ascending dose, single-blind study conducted in 28 adult male and female subjects at seven sites in the United States. Foslevodopa/foscarbidopa was administered via abdominal SC infusion in PD patients over 72 hours. Patients were stratified in 4 groups and received a fixed dose of foslevodopa/foscarbidopa based on their oral daily LD intake. Serial plasma PK samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. Results: LD exposure quickly reached steady state and remained stable with minimal fluctuations. Foslevodopa/foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups. Conclusion: Foslevodopa/foscarbidopa was able to provide stable LD and CD exposures in PD patients over 72 hours via SC route of delivery with very low fluctuation in LD concentration level across a wide range of clinically relevant exposures. Foslevodopa/foscarbidopa had a favorable safety profile. The low PK fluctuation following foslevodopa/foscarbidopa infusion is expected to maintain LD exposure to treat aPD patients within a narrow therapeutic window.

Newly Approved and Investigational Drugs for Motor Symptom Control in Parkinson's Disease

“…To date, a Phase 1 tolerability and pharmacokinetic study showed that a 72-h dose-proportional, continuous subcutaneous infusion of foslevodopa/foscarbidopa achieved a steady-state levodopa exposure rapidly with a degree of fluctuation comparable to LCIG. Akin to other subcutaneous interventions described earlier, the main side effect was skin reaction at the injection/infusion site [ 115 ].…”

The New Developing Treatment of Parkinson’s Disease

“…This way is being studied to treat advanced PD where motor symptoms are not controlled by oral levodopa/carbidopa. The phase Ⅰ of clinical had proved its safety and pretty tolerance [16]. The study about ABBV-951 in the phase Ⅲ showed it was statistically superior to oral levodopa/carbidopa in reducing the motor fluctuations in patients with advanced PD.…”

Effective Management of “OFF” Episodes in Parkinson’s Disease: Emerging Treatment Strategies and Unmet Clinical Needs

“… 112 ABBV-951 is a phosphate prodrug of CD/LD that appears more stable and is at a near neutral pH, thus avoiding excessive skin irritation. 113 Lastly, Dizlin pharmaceuticals is currently developing DZ102, which consists of a stock solution (CD/LD dissolved at a low pH) and a buffer that brings the solution to a physiologically favorable pH when mixed. 111 The stock solution is stable at room temperature for >3 months and the buffered mixture allows for better skin tolerability.…”