P0524 - Pharmacokinetics (PK), Safety, and Tolerability of Etrasimod (APD334) in Participants With Mild, Moderate, or Severe Hepatic Impairment: A Single-Dose, Open-Label, Parallel-Group Study

Caroline Lee, PhD, Yong Tang, PhD, Cassandra Schroeder, , Jinkun Zhang, PhD, Thai Nguyen-Cleary, MD, Michael Ma, MS, Naomi Lyon, , John S. Grundy, PhD
Arena Pharmaceuticals, Inc., San Diego, CA

Introduction: Etrasimod, an oral, selective sphingosine 1-phosphate receptor 1, 4, 5 modulator, is in development for various chronic immune-mediated inflammatory diseases. This study evaluated the effect of hepatic impairment on the PK, safety, and tolerability of etrasimod.

Methods: This open-label, parallel-group study included 36 participants (aged 18-80 years; body mass index ≥18) with normal (n=14 total) or impaired hepatic function (mild=5-6 [n=8], moderate=7-9 [n=8], severe=10-14 [n=6]). The first participant with severe hepatic impairment was enrolled after ≥2 participants with mild hepatic impairment and ≥2 participants with moderate hepatic impairment had been enrolled and followed for ≥48 hours after dosing to ensure no significant safety signals were observed. On Day 1, participants received a single oral dose of etrasimod 2mg after ≥10-hour fast. PK and safety data were collected over 21 days.

Results: Thirty-six participants were enrolled and dosed; 35 completed the study. Compared with their respective demographically matched normal control groups, single dose etrasimod peak exposure (C_max) was comparable for all hepatic impairment groups, whereas etrasimod total exposure (AUC) measures were progressively higher (up to 57.3% higher) in the mild, moderate, and severe hepatic impairment groups (Table). Unbound etrasimod C_max values were progressively lower (up to 42.0% lower) in the mild, moderate, and severe hepatic impairment groups, whereas unbound etrasimod AUC values were typically comparable for all hepatic impairment groups relative to their respective demographically matched normal control groups. Etrasimod t_1/2 only moderately increased as hepatic function decreased, with mean values ranging from 43.9 to 59.5 hours in the demographically matched normal control groups vs 55.7, 69.7, and 76.5 hours in the mild, moderate, and severe hepatic impairment groups, respectively. A single oral dose of etrasimod was well tolerated. There were no clinically significant safety findings when etrasimod was administered to participants with normal hepatic function or participants with mild, moderate, or severe hepatic impairment.

Discussion: A single oral dose of etrasimod 2mg was well tolerated, with relatively modest changes in etrasimod exposure in participants with mild, moderate, or severe hepatic impairment compared with normal controls. These results suggest etrasimod dose adjustment may not be warranted in patients with hepatic impairment.


Disclosures:


Caroline Lee, PhD, Yong Tang, PhD, Cassandra Schroeder, , Jinkun Zhang, PhD, Thai Nguyen-Cleary, MD, Michael Ma, MS, Naomi Lyon, , John S. Grundy, PhD. P0524 - Pharmacokinetics (PK), Safety, and Tolerability of Etrasimod (APD334) in Participants With Mild, Moderate, or Severe Hepatic Impairment: A Single-Dose, Open-Label, Parallel-Group Study, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.