Pharmacokinetics and Safety of Single‐Dose Apraglutide in Individuals with Normal and Impaired Hepatic Function: A Phase 1, Open‐Label Trial

Abstract Intestinal failure‐associated liver disease occurs in 20% to 30% of patients with short bowel syndrome and intestinal failure (SBS‐IF). Apraglutide is a glucagon‐like peptide‐2 (GLP‐2) analog in clinical development for the treatment of patients with SBS‐IF. This study assessed the potential for changes in exposure of apraglutide in individuals with impaired hepatic function versus healthy volunteers. In this Phase 1, open‐label, nonrandomized, single‐dose trial, apraglutide 3.5 mg was administered to participants with moderate hepatic impairment (Child‐Pugh B) or normal hepatic function. Primary pharmacokinetic endpoints were area under the plasma concentration–time curve (AUC) from time 0 to infinity (AUC inf ) or AUC from time 0 to last quantifiable concentration (AUC last ) if AUC inf could not be reliably estimated, AUC 0–168 h , and maximum observed plasma concentration (C max ). Secondary endpoints included safety and tolerability. Each group comprised eight participants. No increased apraglutide exposure was observed in individuals with moderate hepatic impairment. A lower C max and AUC inf of apraglutide was observed in individuals with moderate hepatic impairment versus those with normal hepatic function (C max = 58.7 vs 71.3 ng/mL; AUC inf = 4086 vs 5351 h ng/mL, respectively). The respective geometric mean ratios were 0.835 and 0.936 for C max and AUC inf , and the upper bounds of their 90% confidence intervals indicate that participants with moderate hepatic impairment were not overexposed to apraglutide versus those with normal hepatic function. Adverse events were mild or moderate in severity. The results of this trial suggest that apraglutide does not require dose alteration in patients with mild and moderate hepatic impairment.