Pharmacokinetics, Safety, and Tolerability of Glepaglutide, a Long-Acting GLP-2 Analog, in Subjects with Renal Impairment.

Abstract

Glepaglutide is a novel, ready-to-use, long-acting, glucagon-like peptide-2 (GLP-2) analog intended for the treatment of patients with short bowel syndrome (SBS). This study investigated the impact of renal function on the pharmacokinetics and safety of glepaglutide. In this 3-site, non-randomized, open-label study, 16 subjects were enrolled: 4 with severe renal impairment (eGFR 15 to < 30mL/min/1.73m2), 4with end stage renal disease (ESRD) not on dialysis (eGFR < 15mL/min/1.73m2), and 8 matching controls with normal renal function (eGFR ≥ 90mL/min/1.73m2). Blood samples were collected over a 14-day period following a single subcutaneous (SC) dose of glepaglutide 10mg. Safety and tolerability were assessed throughout the study. The primary pharmacokinetic parameters were area under the curve between dosing and 168h (AUC0-168h) and the maximum plasma concentration (Cmax). There was no clinically relevant difference between subjects with severe renal impairment/ESRD and normal renal function with respect to total exposure (AUC0-168h) and peak plasma concentrations (Cmax) of glepaglutide following a single SC dose. A single SC dose of glepaglutide 10mg appeared safe and well tolerated in subjects with normal renal function and subjects with severe renal impairment or ESRD. No serious adverse events were reported, and no safety issues were identified. No difference in glepaglutide pharmacokinetics was seen between renal impaired and normal subjects. Based on this trial, dose adjustment appears not to be warranted in SBS patients with renal impairment. The trial is registered at http://www. gov (NCT04178447) and has the EudraCT number: 2019-001466-15.