FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308134482> ?p ?o ?g. }

• W4308134482 endingPage "A547" @default.
• W4308134482 startingPage "A547" @default.
• W4308134482 abstract "Abstract Background Relacorilant is a highly selective glucocorticoid receptor (GR) modulator in development for the treatment of endogenous Cushing syndrome (CS). Unlike the FDA-approved GR antagonist mifepristone, relacorilant lacks affinity for the progesterone and other receptors. In a phase 2 study in patients with CS (NCT02804750, Pivonello et al, 2021), relacorilant provided clinically meaningful changes in a number of cortisol-excess-related comorbidities, including hypertension and hyperglycemia, without undesirable antiprogesterone effects or drug-induced hypokalemia. Currently, 4 clinical studies of relacorilant in patients with CS are ongoing: GRACE (NCT03697109), a phase 3 trial enrolling patients with endogenous CS of all etiologies; GRADIENT (NCT04308590), a phase 3 trial focusing on hypercortisolism due to adrenal adenomas or hyperplasia; a phase 2/3 long-term extension study (NCT03604198); and a phase 1b study in patients with adrenocortical carcinoma associated with glucocorticoid excess (NCT04373265). Here, we report safety results and liver function test (LFT) changes from open-label phase 1 and 2 studies of relacorilant in healthy and hepatically impaired adults and in adult patients with CS. Methods In a special population study, 9 subjects with moderate hepatic impairment (Child-Pugh Class B) and 9 matched controls with normal hepatic function received relacorilant (300 mg QD) for 10 days. In a phase 1 fixed-sequence drug-drug interaction study (NCT03512548), 28 healthy subjects received relacorilant (300 mg QD) for 10 days followed by 10 days of relacorilant (300 mg QD) combined with itraconazole (200 mg QD). Thirty-five patients with CS received relacorilant (100–400 mg QD) for up to 16 weeks in the phase 2 study. Results While relacorilant is eliminated primarily through the hepatic route, no apparent difference in relacorilant pharmacokinetics in subjects with moderate hepatic impairment vs matched controls was observed, with relacorilant exposures (as measured by area under the concentration-time curve [AUC] and maximum concentration [Cmax]) largely overlapping across both groups. In addition, reductions in LFTs were observed in this study. In healthy adults treated with relacorilant followed by relacorilant + itraconazole (an agent with reported liver toxicity), a similar trend toward reduced LFTs was seen throughout the study. In the phase 2 study in patients with CS, reductions in LFTs were also observed, including normalization of LFTs in some patients with abnormal values at baseline. Conclusions These results suggest that relacorilant has a favorable liver safety profile that includes a trend toward improved LFTs in volunteers and patients with normal and abnormal liver function. The findings of the hepatic impairment study support the use of relacorilant without dose adjustment in patients with moderate hepatic impairment. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m." @default.
• W4308134482 created "2022-11-08" @default.
• W4308134482 creator A5036632288 @default.
• W4308134482 creator A5041262913 @default.
• W4308134482 creator A5048191133 @default.
• W4308134482 date "2022-11-01" @default.
• W4308134482 modified "2023-10-16" @default.
• W4308134482 title "PMON165 Favorable Liver Safety Profile of the Selective Glucocorticoid Receptor Modulator Relacorilant in Healthy and Hepatically Impaired Adults and in Patients with Cushing Syndrome" @default.
• W4308134482 doi "https://doi.org/10.1210/jendso/bvac150.1137" @default.
• W4308134482 hasPublicationYear "2022" @default.
• W4308134482 type Work @default.
• W4308134482 citedByCount "0" @default.
• W4308134482 crossrefType "journal-article" @default.
• W4308134482 hasAuthorship W4308134482A5036632288 @default.
• W4308134482 hasAuthorship W4308134482A5041262913 @default.
• W4308134482 hasAuthorship W4308134482A5048191133 @default.
• W4308134482 hasBestOaLocation W43081344822 @default.
• W4308134482 hasConcept C126322002 @default.
• W4308134482 hasConcept C134018914 @default.
• W4308134482 hasConcept C2778826759 @default.
• W4308134482 hasConcept C2779234561 @default.
• W4308134482 hasConcept C2780841215 @default.
• W4308134482 hasConcept C2908647359 @default.
• W4308134482 hasConcept C31760486 @default.
• W4308134482 hasConcept C535046627 @default.
• W4308134482 hasConcept C54355233 @default.
• W4308134482 hasConcept C59493245 @default.
• W4308134482 hasConcept C71924100 @default.
• W4308134482 hasConcept C86803240 @default.
• W4308134482 hasConcept C90924648 @default.
• W4308134482 hasConcept C99454951 @default.
• W4308134482 hasConceptScore W4308134482C126322002 @default.
• W4308134482 hasConceptScore W4308134482C134018914 @default.
• W4308134482 hasConceptScore W4308134482C2778826759 @default.
• W4308134482 hasConceptScore W4308134482C2779234561 @default.
• W4308134482 hasConceptScore W4308134482C2780841215 @default.
• W4308134482 hasConceptScore W4308134482C2908647359 @default.
• W4308134482 hasConceptScore W4308134482C31760486 @default.
• W4308134482 hasConceptScore W4308134482C535046627 @default.
• W4308134482 hasConceptScore W4308134482C54355233 @default.
• W4308134482 hasConceptScore W4308134482C59493245 @default.
• W4308134482 hasConceptScore W4308134482C71924100 @default.
• W4308134482 hasConceptScore W4308134482C86803240 @default.
• W4308134482 hasConceptScore W4308134482C90924648 @default.
• W4308134482 hasConceptScore W4308134482C99454951 @default.
• W4308134482 hasIssue "Supplement_1" @default.
• W4308134482 hasLocation W43081344821 @default.
• W4308134482 hasLocation W43081344822 @default.
• W4308134482 hasOpenAccess W4308134482 @default.
• W4308134482 hasPrimaryLocation W43081344821 @default.
• W4308134482 hasRelatedWork W1975968177 @default.
• W4308134482 hasRelatedWork W2034583712 @default.
• W4308134482 hasRelatedWork W2071337848 @default.
• W4308134482 hasRelatedWork W2078471485 @default.
• W4308134482 hasRelatedWork W2092107317 @default.
• W4308134482 hasRelatedWork W2097516685 @default.
• W4308134482 hasRelatedWork W2109154705 @default.
• W4308134482 hasRelatedWork W2170009353 @default.
• W4308134482 hasRelatedWork W2276893008 @default.
• W4308134482 hasRelatedWork W4232773839 @default.
• W4308134482 hasVolume "6" @default.
• W4308134482 isParatext "false" @default.
• W4308134482 isRetracted "false" @default.
• W4308134482 workType "article" @default.