To demonstrate that continuous subcutaneous infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson’s disease (PD) patients who are not well controlled on oral medication.
Foslevodopa/foscarbidopa are prepared and equilibrium solubility and chemical stability are examined in aqueous media of different pHs. Solutions of foslevodopa/foscarbidopa (4:1 to 20:1 ratios) were prepared by dissolving pH-adjusted lyophilized materials in water and infused subcutaneously in healthy volunteers for up to 72 hours. Frequent blood samples were collected to measure LD and CD exposure and safety was monitored throughout the study.
Foslevodopa/foscarbidopa (ABBV-951), demonstrates high water solubility and excellent chemical stability near physiological pH enabling continuous subcutaneous infusion therapy. Following subcutaneous infusion, a stable LD pharmacokinetic (PK) profile was maintained for up to 72 hours and the infusion was well tolerated.
Preparation of foslevodopa and foscarbidopa enables preclinical and clinical PK, safety, and tolerability studies in support of their advancement for the treatment of PD. In Phase 1 clinical trials, foslevodopa/foscarbidopa demonstrates consistent and stable LD plasma exposure supporting further studies of this treatment as a potentially transformational option for those suffering from PD. This article is protected by copyright. All rights reserved.