2699-LB: Renal Function Does Not Affect Pilavapadin Pharmacokinetics: Results from a Phase 1, Open-Label, Parallel-Group Study

Introduction and Objective: Pilavapadin, an oral adaptor protein 2-associated kinase 1 (AAKI) inhibitor, has demonstrated potential as treatment of diabetic peripheral neuropathic pain. Pharmacokinetics (PK) of pilavapadin are important as it is likely to be in patients with renal impairment. The objective was to evaluate the effect of renal impairment on the PK of pilavapadin. Methods: Participants were enrolled into groups applying estimated creatinine clearance (CrCl) mL/min using the Cockcroft-Gault equation: 1 Normal Renal Function (CrCl ≥ 90), 2 Mild Impairment (CrCl ≥ 60 to < 90), 3a Moderate Impairment (CrCl ≥ 45 to < 60), and 3b Moderate Impairment (CrCl ≥ 30 to <45). Participants were confined to the study site from Day -1 to Day 7, then assessed weekly as an outpatient until Day 49. Results: 37 patients (46% female with mean age = 61.5 yrs and BMI = 30.0) were enrolled (13 in the normal renal function group and 8 in each renal group). Systemic exposure [Area Under the Curve (AUC 0-24h h*ng/mL) for Ratio of Geometric Means (GMR) with 90% CI] observed in Groups 2, 3a, and 3b compared to Group 1 were 0.85 (0.74, 0.97), 0.94 (0.80, 1.11), 0.81 (0.61, 1.07), respectively, demonstrating comparable overall exposure. Similarly, the mean PK profile from time 0 to 144 hrs demonstrated overlapping profiles (figure). Conclusion: Mild to moderate renal impairment does not have a meaningful effect on the PK and safety of pilavapadin in patients with CrCl ≥ 30 mL/min. Disclosure R. Pop-Busui: Board Member; Current; American Diabetes Association. Consultant; Current; Averitas Pharma, Inc. Research Support; Current; Bayer AG. Consultant; Current; Lexicon Pharmaceuticals, Inc. Research Support; Current; National Institutes of Health. Consultant; Current; Novo Nordisk, Roche Diagnostics, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Viatris Inc. M.B. Hardin: Employee; Current; Lexicon Pharmaceuticals, Inc. C. Granowitz: Employee; Current; Lexicon Pharmaceuticals, Inc. P. Pierce: Employee; Current; Lexicon Pharmaceuticals, Inc. S. Gopinathan: Employee; Current; Lexicon Pharmaceuticals, Inc.