FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4365512075> ?p ?o ?g. }

• W4365512075 endingPage "CT192" @default.
• W4365512075 startingPage "CT192" @default.
• W4365512075 abstract "Abstract Background: Futibatinib, an irreversible FGFR1-4 inhibitor, is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangements. As the primary elimination pathway for futibatinib is hepatic metabolism, we conducted a phase 1 study to evaluate the effect of hepatic impairment (HI) on futibatinib pharmacokinetics (PK) and safety in healthy adults. Methods: A single oral dose of 20 mg futibatinib was administered to adult subjects with mild (Child-Pugh score, 5-6), moderate (7-9), or severe (10-15) HI. Control healthy subjects were matched to each HI cohort according to age, body mass index, and sex. Intensive PK samples were collected up to 72 hours post-dose. Exposure measures (AUC0-inf, AUC0-t, and Cmax) in subjects with HI were compared with matching control cohorts and with the overall healthy-control cohort. Relationships between plasma PK and HI were examined graphically via scatter/regression plots of PK parameters versus baseline Child-Pugh score, bilirubin, albumin, international normalized ratio, and aspartate aminotransferase. Results: Overall, 38 subjects were enrolled (mild HI, n = 8; moderate HI, n = 8; severe HI, n = 6; healthy controls, n = 16). Following the administration of futibatinib, no trend was observed between the severity of HI and the extent of futibatinib exposure increase. Compared with matched controls, AUC0-inf increased by 21%, 20% and 18%, and Cmax by 43%, 15%, and 10% in subjects with mild, moderate, and severe HI, respectively. Changes in exposure were not considered clinically relevant as geometric mean ratios were within 80-125% bioequivalence limits, except for Cmax in subjects with mild HI (43%). Futibatinib PK parameters and HI measures did not appear to be associated based on visual inspection or statistical evaluation of regression plots (p-values all &gt; 0.05). No subjects discontinued from the study due to treatment-emergent adverse events (TEAEs). Overall, two (12.5%) subjects in the healthy-control cohort reported one Grade 1 TEAE each (dyspepsia and headache) and two (25.0 %) subjects in the mild HI cohort each reported one Grade 1 TEAE (toothache and headache). All TEAEs were considered related to treatment. No subjects with moderate/severe HI reported TEAEs. Conclusions: No clinically meaningful differences in the systemic plasma exposure of futibatinib were observed based on the severity of HI. Single oral doses of futibatinib were well tolerated among subjects with varying degrees of HI and matched healthy adult subjects in this study. The data suggest that dose adjustment may not be necessary in patients with HI receiving futibatinib 20 mg QD for its approved indication. Citation Format: Ling Gao, Ikuo Yamamiya, Mark Pinti, Juan Carlos Rondón, Thomas Marbury, Gareth Tomlinson, Lukas Makris, Nanae Hangai, Volker Wacheck. Phase 1, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib in adult subjects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT192." @default.
• W4365512075 created "2023-04-15" @default.
• W4365512075 creator A5002628390 @default.
• W4365512075 creator A5009244604 @default.
• W4365512075 creator A5012608968 @default.
• W4365512075 creator A5028366409 @default.
• W4365512075 creator A5029779552 @default.
• W4365512075 creator A5047754769 @default.
• W4365512075 creator A5055673941 @default.
• W4365512075 creator A5058426048 @default.
• W4365512075 creator A5071766381 @default.
• W4365512075 date "2023-04-14" @default.
• W4365512075 modified "2023-09-25" @default.
• W4365512075 title "Abstract CT192: Phase 1, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib in adult subjects" @default.
• W4365512075 doi "https://doi.org/10.1158/1538-7445.am2023-ct192" @default.
• W4365512075 hasPublicationYear "2023" @default.
• W4365512075 type Work @default.
• W4365512075 citedByCount "0" @default.
• W4365512075 crossrefType "journal-article" @default.
• W4365512075 hasAuthorship W4365512075A5002628390 @default.
• W4365512075 hasAuthorship W4365512075A5009244604 @default.
• W4365512075 hasAuthorship W4365512075A5012608968 @default.
• W4365512075 hasAuthorship W4365512075A5028366409 @default.
• W4365512075 hasAuthorship W4365512075A5029779552 @default.
• W4365512075 hasAuthorship W4365512075A5047754769 @default.
• W4365512075 hasAuthorship W4365512075A5055673941 @default.
• W4365512075 hasAuthorship W4365512075A5058426048 @default.
• W4365512075 hasAuthorship W4365512075A5071766381 @default.
• W4365512075 hasConcept C112705442 @default.
• W4365512075 hasConcept C126322002 @default.
• W4365512075 hasConcept C22979827 @default.
• W4365512075 hasConcept C2777501473 @default.
• W4365512075 hasConcept C2777513400 @default.
• W4365512075 hasConcept C2780221984 @default.
• W4365512075 hasConcept C71924100 @default.
• W4365512075 hasConcept C72563966 @default.
• W4365512075 hasConcept C90924648 @default.
• W4365512075 hasConceptScore W4365512075C112705442 @default.
• W4365512075 hasConceptScore W4365512075C126322002 @default.
• W4365512075 hasConceptScore W4365512075C22979827 @default.
• W4365512075 hasConceptScore W4365512075C2777501473 @default.
• W4365512075 hasConceptScore W4365512075C2777513400 @default.
• W4365512075 hasConceptScore W4365512075C2780221984 @default.
• W4365512075 hasConceptScore W4365512075C71924100 @default.
• W4365512075 hasConceptScore W4365512075C72563966 @default.
• W4365512075 hasConceptScore W4365512075C90924648 @default.
• W4365512075 hasIssue "8_Supplement" @default.
• W4365512075 hasLocation W43655120751 @default.
• W4365512075 hasOpenAccess W4365512075 @default.
• W4365512075 hasPrimaryLocation W43655120751 @default.
• W4365512075 hasRelatedWork W116933167 @default.
• W4365512075 hasRelatedWork W1965995300 @default.
• W4365512075 hasRelatedWork W2002994412 @default.
• W4365512075 hasRelatedWork W2016027692 @default.
• W4365512075 hasRelatedWork W2018072197 @default.
• W4365512075 hasRelatedWork W2021282652 @default.
• W4365512075 hasRelatedWork W2023399949 @default.
• W4365512075 hasRelatedWork W2086568388 @default.
• W4365512075 hasRelatedWork W2135200370 @default.
• W4365512075 hasRelatedWork W4220960064 @default.
• W4365512075 hasVolume "83" @default.
• W4365512075 isParatext "false" @default.
• W4365512075 isRetracted "false" @default.
• W4365512075 workType "article" @default.