In:
Clinical Pharmacology in Drug Development, Wiley, Vol. 10, No. 7 ( 2021-07), p. 707-717
Abstract:
This phase I open‐label trial (NCT03627754) assessed glasdegib pharmacokinetics and safety in otherwise healthy participants with moderate (Child‐Pugh B) or severe (Child‐Pugh C) hepatic impairment. Participants with hepatic impairment and age/weight‐matched controls with normal hepatic function received a single oral 100‐mg glasdegib dose under fasted conditions. The primary end points were area under the plasma concentration–time curve from time zero to infinity (AUC inf ) and maximum plasma concentration (C max ). Twenty‐four participants (8/cohort) were enrolled. Glasdegib plasma exposures in moderate hepatic impairment were similar to controls, with adjusted geometric mean ratios (GMRs) of 110.8% (90% confidence interval [CI], 78.0–157.3) for AUC inf and 94.8% (69.9–128.4) for C max versus controls. In severe hepatic impairment, glasdegib plasma exposures were lower than controls (AUC inf GMR, 75.7%; 90%CI, 51.5–111.0; C max GMR, 58.0%; 90%CI, 37.8–89.0). Unbound glasdegib exposures were similar to controls for moderate (AUC inf,u GMR, 118.1%; 90%CI, 88.7–157.2; C max,u GMR, 101.1%; 90%CI, 78.4–130.3) and severe hepatic impairment (AUC inf,u GMR, 116.3%; 90%CI 81.8–165.5; C max,u GMR, 89.2%, 90%CI, 60.2–132.3). No treatment‐related adverse events or clinically significant changes in laboratory values, vital signs, or electrocardiograms were observed. Together with previous findings, this suggests glasdegib dose modifications are not required based on hepatic impairment.
Type of Medium:
Online Resource
ISSN:
2160-763X
,
2160-7648
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2649010-9
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