Pharmacokinetics, safety, and tolerability of fedratinib in adults with moderate and severe hepatic impairment: results from the phase 1 FEDR-CP-001 trial.

Abstract

Purpose: The FEDR-CP-001 (NCT03983161) trial evaluated the pharmacokinetics (PK) and safety of a single dose of fedratinib in adults with moderate or severe hepatic impairment (HI) compared with matched healthy participants with normal hepatic function.

Methods: This was a non-randomized, open-label, multicenter, phase 1 trial. Participants were aged 18-75 years and had a BMI of 18-40 kg/m². HI was determined by Child-Pugh score. Participants were placed into 1 of the following groups: group 1, moderate HI; group 2, healthy participants matched to group 1; group 3, severe HI; and group 4, healthy participants matched to group 3. Participants received a single dose of fedratinib 300 mg (groups 1 and 2) or 200 mg (groups 3 and 4) and were followed for 21 days.

Results: All participants (N = 38; groups 1, 3, and 4 [n = 8 each], group 2 [n = 14]) completed the trial. Peak and total fedratinib exposures (C_max, AUC_0-∞) were similar between moderate HI versus matched healthy participants. In participants with severe HI, there were lower total exposures compared to the matched healthy participants where the ratios of geometric means for C_max, and AUC_0-∞ were 0.897 and 0.660, respectively, and with large inter-participant variability. Ten participants experienced a treatment-emergent adverse event (all were considered mild), which were evenly distributed across groups.

Conclusion: These data indicate that reducing fedratinib starting doses is not necessary for patients with moderate or severe HI, and support clinicians in regular monitoring of patients with HI taking fedratinib.