Kidney Week

Abstract: FR-PO080

Crossover Study Comparing Bioavailability of Captisol-Enabled (CE) Iohexol Injection with Reference Iohexol Injection in Healthy Subjects

Session Information

• AKI: Clinical Outcomes, Trials
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Marschke, Keith, Ligand Pharmaceuticals Incorporated, San Diego, California, United States

Keith Marschke,

• Antle, Vincent, Ligand Pharmaceuticals Incorporated, San Diego, California, United States

Vincent Antle,

• Vajda, Eric G., Ligand Pharmaceuticals Incorporated, San Diego, California, United States

Eric G. Vajda,

• Zhi, Lin, Ligand Pharmaceuticals Incorporated, San Diego, California, United States

Lin Zhi,

• Cushing, Daniel, Medical and Regulatory Affairs, Phoenixville, Pennsylvania, United States

Daniel Cushing,

• Pipkin, James, Ligand Pharmaceuticals Incorporated, San Diego, California, United States

James Pipkin,

Background

Iodinated contrast agents may place patients with certain risk factors at an increased risk for acute kidney injury during cardiac imaging procedures.¹ Studies in renally-compromised mice and rats demonstrated that the addition of sulfobutylether β-cyclodextrin (Captisol^®) to a clinically administered dose of Iohexol significantly reduced renal pathology scores, and increased survival in rats from 50% to 88%.² A Phase 1, single-center, randomized, double-blind, two-period crossover study was conducted to determine relative bioavailability of CE-Iohexol and a reference Iohexol injection (OMNIPAQUE™) after intravenous (IV) administration in healthy adults.

Methods

A total of 24 subjects were enrolled in the study as 2 groups of 12 subjects in 2 treatment periods. Subjects received each of the following treatments as a single IV dose (80 mL infused over 20 seconds): CE-Iohexol -755 mg/mL iohexol (350 mgI/mL)/50 mg CAPTISOL/mL; OMNIPAQUE - 755 mg/mL iohexol (350 mgI/mL). Serial blood samples were collected for Iohexol plasma concentration determination, and safety was assessed during the 48 hours following each dose. Subjects were discharged on day 3.

Results

22 subjects completed the study; 2 subjects were withdrawn for technical reasons. Bioequivalence was demonstrated by calculation of geometric mean ratios (GMR) between CE-Iohexol and OMNIPAQUE for key pharmacokinetic parameters. GMR of the area under the concentration-time curve for time 0-infinity (AUC_0-inf) was 1.00 (90% confidence interval [CI], 0.98-1.02). GMR of the maximum concentration (C_max) was 1.00 (90% CI, 0.95-1.06). Other PK parameters, including time to maximum observed concentration (T_max), half-life (t_½) and elimination rate constant (K_el) were similar between treatments. All treatment-emergent adverse events during the study were mild to moderate in severity. No subject had a serious adverse event or discontinued from the study due to an adverse event.

Conclusion

The observed PK profile supports clinical development of CE-Iohexol as a next-generation contrast agent with a reduced risk of renal toxicity (NCT03869983).
¹ McCullough PA, et al. J Am College of Cardiology 2016;68:1465-73
² Rowe ES, et al. J Neuroimaging. 2016;26:511-518.

Funding

• Commercial Support – Ligand Pharmaceuticals Incorporated