Effect of itraconazole, food, and ethnic origin on the pharmacokinetics of ivosidenib in healthy subjects.
Purpose: To assess the effect of ethnicity, food, and itraconazole (strong CYP3A4 inhibitor) on the pharmacokinetics of ivosidenib after single oral doses in healthy subjects. Methods: Three phase 1 open-label studies were performed. Study 1: Japanese and Caucasian subjects received single doses of...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 75; no. 8; pp. 1099 - 1109 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Aug2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137507147&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137507147 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Aug2019 vid: 75 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 137507147 137507147 137507147 10.1007/s00228-019-02673-6 137507147 ppf: 1099 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Effect of itraconazole, food, and ethnic origin on the pharmacokinetics of ivosidenib in healthy subjects. aug: au: Dai, David Yang, Hua Nabhan, Salah Liu, Hua Hickman, Denice Liu, Guowen Zacher, Jeffrey Vutikullird, Apinya Prakash, Chandra Agresta, Samuel Bowden, Chris Fan, Bin affil: Agios Pharmaceuticals, Inc., 88 Sidney Street, 02139, Cambridge, MA, USA sug: subj: Itraconazole Pharmacodynamics Meals Japan Ethnic Groups Japan Enzyme Inhibitors Pharmacokinetics Enzyme Inhibitors Administration and Dosage Itraconazole Administration and Dosage Drug Interactions Human Randomized Controlled Trials Crossover Design Fasting Fats Administration, Oral Japan White Persons Confidence Intervals ab: Purpose: To assess the effect of ethnicity, food, and itraconazole (strong CYP3A4 inhibitor) on the pharmacokinetics of ivosidenib after single oral doses in healthy subjects. Methods: Three phase 1 open-label studies were performed. Study 1: Japanese and Caucasian subjects received single doses of 250, 500, or 1000 mg ivosidenib (NCT03071770). Part 1 of study 2 (a two-period crossover study): subjects received 500 mg ivosidenib after either an overnight fast or a high-fat meal. Subjects received 1000 mg ivosidenib after an overnight fast in the single period of part 2 (NCT02579707). Study 3: in period 1, subjects received 250 mg ivosidenib; then, in period 2, subjects received oral itraconazole (200 mg once daily) on days 1–18, plus 250 mg ivosidenib on day 5 (NCT02831972). Results: Ivosidenib was well tolerated in all three studies. Study 1: pharmacokinetic profiles were generally comparable, although AUC and Cmax were slightly lower in Japanese subjects than in Caucasian subjects, by ~ 30 and 17%, respectively. Study 2: AUC increased by ~ 25% and Cmax by ~ 98%, when ivosidenib was administered with a high-fat meal compared with a fasted state. Study 3: co-administration of itraconazole increased ivosidenib AUC by 169% (90% CI 145–195) but had no effect on ivosidenib Cmax. Conclusions: No ivosidenib dose adjustment is deemed necessary for Japanese subjects. High-fat meals should be avoided when ivosidenib is taken with food. When co-administered with strong CYP3A4 inhibitors, monitoring for QT interval prolongation (a previously defined adverse event of interest) is recommended and an ivosidenib dose interruption or reduction may be considered. ClinicalTrials.gov NCT03071770, NCT02579707, and NCT02831972. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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