The Effect of Renal Impairment on the Pharmacokinetics and Safety of Itacitinib
© 2020 Incyte Corporation. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology..
Itacitinib is a novel, selective, Janus kinase 1 inhibitor in development for treatment of graft-versus-host disease. The objective of this study was to assess pharmacokinetics and safety of 300-mg itacitinib dosed in participants with normal renal function (n = 10), severe renal impairment (n = 8), and end-stage renal disease (ESRD) on hemodialysis (n = 8). Serial plasma and urine samples (urine from normal and severe groups only) were collected before dosing until 72 hours after dosing. In the ESRD group, itacitinib was evaluated in 2 periods, when dosed before (period 1) and after (period 2) a hemodialysis session. Geometric mean ratios (90% confidence interval) in participants with severe renal impairment, ESRD period 1 and ESRD period 2 relative to participants with normal renal function were 1.65 (1.13-2.39), 0.71 (0.49-1.03), and 0.83 (0.57-1.20) for maximum plasma drug concentration and 2.23 (1.56-3.18), 0.81 (0.57-1.16), and 0.95 (0.66-1.35) for area under the plasma concentration-time curve from time zero to infinity. Itacitinib was well tolerated, and 3 grade 1 treatment-emergent adverse events were reported over the course of the study. Given the magnitude of exposure changes in participants with severe renal impairment or ESRD and the historic risk-benefit profile, no dose adjustment is recommended for itacitinib in patients with impaired renal function, although the final dosage recommendation will be based on cumulative pharmacokinetics and safety from this study and from the pivotal graft-versus-host disease trial. Additionally, itacitinib may be administered to patients undergoing dialysis regardless of the time of dialysis.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
|---|---|
| Enthalten in: |
Journal of clinical pharmacology - 60(2020), 8 vom: 16. Aug., Seite 1022-1029 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Srinivas, Nithya [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.07.2021 Date Revised 30.07.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/jcph.1601 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM30737758X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM30737758X | ||
| 003 | DE-627 | ||
| 005 | 20231225125429.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jcph.1601 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1024.xml |
| 035 | |a (DE-627)NLM30737758X | ||
| 035 | |a (NLM)32149388 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Srinivas, Nithya |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Effect of Renal Impairment on the Pharmacokinetics and Safety of Itacitinib |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.07.2021 | ||
| 500 | |a Date Revised 30.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 Incyte Corporation. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology. | ||
| 520 | |a Itacitinib is a novel, selective, Janus kinase 1 inhibitor in development for treatment of graft-versus-host disease. The objective of this study was to assess pharmacokinetics and safety of 300-mg itacitinib dosed in participants with normal renal function (n = 10), severe renal impairment (n = 8), and end-stage renal disease (ESRD) on hemodialysis (n = 8). Serial plasma and urine samples (urine from normal and severe groups only) were collected before dosing until 72 hours after dosing. In the ESRD group, itacitinib was evaluated in 2 periods, when dosed before (period 1) and after (period 2) a hemodialysis session. Geometric mean ratios (90% confidence interval) in participants with severe renal impairment, ESRD period 1 and ESRD period 2 relative to participants with normal renal function were 1.65 (1.13-2.39), 0.71 (0.49-1.03), and 0.83 (0.57-1.20) for maximum plasma drug concentration and 2.23 (1.56-3.18), 0.81 (0.57-1.16), and 0.95 (0.66-1.35) for area under the plasma concentration-time curve from time zero to infinity. Itacitinib was well tolerated, and 3 grade 1 treatment-emergent adverse events were reported over the course of the study. Given the magnitude of exposure changes in participants with severe renal impairment or ESRD and the historic risk-benefit profile, no dose adjustment is recommended for itacitinib in patients with impaired renal function, although the final dosage recommendation will be based on cumulative pharmacokinetics and safety from this study and from the pivotal graft-versus-host disease trial. Additionally, itacitinib may be administered to patients undergoing dialysis regardless of the time of dialysis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Janus kinase inhibitor | |
| 650 | 4 | |a dialysis | |
| 650 | 4 | |a graft-versus-host disease | |
| 650 | 4 | |a itacitinib | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a renal impairment | |
| 650 | 7 | |a Acetonitriles |2 NLM | |
| 650 | 7 | |a Blood Proteins |2 NLM | |
| 650 | 7 | |a Dialysis Solutions |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Pyrroles |2 NLM | |
| 650 | 7 | |a itacitinib |2 NLM | |
| 650 | 7 | |a 19J3781LPM |2 NLM | |
| 650 | 7 | |a Janus Kinase 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.2 |2 NLM | |
| 700 | 1 | |a Barbour, April M |e verfasserin |4 aut | |
| 700 | 1 | |a Epstein, Noam |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Gongfu |e verfasserin |4 aut | |
| 700 | 1 | |a Petusky, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Xun, Zhinyin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuska, Brad |e verfasserin |4 aut | |
| 700 | 1 | |a Marbury, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xuejun |e verfasserin |4 aut | |
| 700 | 1 | |a Yeleswaram, Swamy |e verfasserin |4 aut | |
| 700 | 1 | |a Punwani, Naresh |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of clinical pharmacology |d 1973 |g 60(2020), 8 vom: 16. Aug., Seite 1022-1029 |w (DE-627)NLM000005576 |x 1552-4604 |7 nnns |
| 773 | 1 | 8 | |g volume:60 |g year:2020 |g number:8 |g day:16 |g month:08 |g pages:1022-1029 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jcph.1601 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 60 |j 2020 |e 8 |b 16 |c 08 |h 1022-1029 | ||