scholarly journals Evaluation of the Pharmacokinetics and Safety of a Single Dose of Acalabrutinib in Subjects With Hepatic Impairment

2021 ◽  
Author(s):  
Yan Xu ◽  
Raquel Izumi ◽  
Helen Nguyen ◽  
Anna Kwan ◽  
Howard Kuo ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment

scholarly journals Single-dose pharmacokinetics of BMS-986177/JNJ-70033093 in participants with mild or moderate hepatic impairment compared to healthy participants

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Perera ◽  
G Abelian ◽  
D Li ◽  
Z Wang ◽  
L Zhang ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Moderate Hepatic Impairment ◽  
Funding Source ◽  
Antithrombotic Agents ◽  
Normal Hepatic Function ◽  
Pugh Class ◽  
Healthy Participants ◽  
Mild Hepatic Impairment

Abstract Background According to the scientific evidence accumulated to date (ie, genetic, epidemiological, preclinical, clinical), the modulation of Factor XI (FXI) function may provide a novel mechanism for systemic anticoagulation without increasing the risk of clinically significant bleeding in a variety of conditions predisposing patients to a high risk of thrombotic or bleeding events. BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) is a small molecule that inhibits the active form of FXI (FXIa) with high affinity and selectivity. Depending on the indication, BMS-177/JNJ-3093 may provide benefit to patients as add-on or potentially replacement therapy to the current standard of care antithrombotic agents. Patients with hepatic impairment may have an increased risk of bleeding when using existing antithrombotic agents and therefore may benefit from drugs with an improved safety profile. Purpose To assess the effect of mild or moderate hepatic impairment on the pharmacokinetic (PK) properties of BMS-177/JNJ-3093. Methods This was a multicenter, open-label, non-randomized, single-dose study. A single 60-mg oral dose of BMS-177/JNJ-3093 was administered to 9 participants with mild hepatic impairment (Child-Pugh class A), 8 participants with moderate hepatic impairment (Child-Pugh class B), and 9 healthy participants with normal hepatic function. Healthy participants were matched to participants with hepatic impairment in each Child-Pugh class with regard to body weight. To assess the effects of hepatic impairment on BMS-177/JNJ-3093 PK, an analysis of variance was performed on the natural log-transformed Cmax, AUC(INF), and AUC(0-T) with hepatic function group as a fixed effect. Results BMS-177/JNJ-3093 was well tolerated when administered as an oral dose of 60 mg in participants with mild or moderate hepatic impairment and healthy participants with normal hepatic function. There were no deaths, serious adverse events (AEs), severe AEs, bleeding AEs, or discontinuations due to an AE reported during the study. The geometric mean ratios (GMRs) (90% CI) comparing mild hepatic impairment to normal hepatic function were 1.180 (0.735, 1.895) and 1.168 (0.725, 1.882) for total BMS-177/JNJ-3093 maximum concentration (Cmax) and area under the curve from time 0 to infinity (AUC(INF)), respectively. The GMRs (90% CI) comparing moderate hepatic impairment to normal hepatic function were 1.140 (0.699, 1.857) and 0.996 (0.609, 1.628) for total BMS-177/JNJ-3093 Cmax and AUC(INF), respectively. Overall, levels of activated partial thromboplastin time (aPTT) increased in an exposure-related manner following single oral doses of 60 mg BMS-177/JNJ-3093 in all groups. Conclusion BMS-177/JNJ-3093 was well tolerated in the normal healthy participants and those with mild or moderate hepatic impairment. The observed changes indicate that a dose adjustment in these populations may not be necessary. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was sponsored by Bristol-Myers Squibb and Janssen Research & Development, LLC

scholarly journals Pharmacokinetics and Safety of Single-Dose Esaxerenone in Japanese Subjects with Mild to Moderate Hepatic Impairment

2019 ◽  
Vol 37 (1) ◽  
pp. 253-264 ◽  
Author(s):  
Akifumi Kurata ◽  
Takafumi Yoshida ◽  
Megumi Inoue ◽  
Tomoko Ishizuka ◽  
Takafumi Nakatsu ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Moderate Hepatic Impairment ◽  
Japanese Subjects

Effect of hepatic impairment on sorafenib pharmacokinetics: Results of a multicenter, open-label, single-dose, phase I trial.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 2580-2580 ◽  
Author(s):  
J. T. Lettieri ◽  
A. L. Mazzu ◽  
L. Huang ◽  
C. D. Lathia
Keyword(s):  
Single Dose ◽  
Phase I ◽  
Hepatic Impairment ◽  
Phase I Trial ◽  
Open Label

scholarly journals A Phase 1, Open-Label, Evaluation of the Single-Dose Pharmacokinetics of Delafloxacin (DLX) in Subjects With and Without Hepatic Impairment

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Randall Hoover ◽  
Megan Quintas ◽  
Laura Lawrence ◽  
Sriram Gunda ◽  
Eugene Sun ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Phase 1 ◽  
Open Label

Open-label, Single-dose Studies of the Pharmacokinetics of Edaravone in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared to Subjects with Normal Hepatic Functioning

2020 ◽  
Vol 42 (8) ◽  
pp. 1467-1482.e4 ◽  
Author(s):  
Yoshinobu Nakamaru ◽  
Masae Kakubari ◽  
Kaori Yoshida ◽  
Makoto Akimoto ◽  
Vesna Todorovic ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Severe Hepatic Impairment ◽  
Open Label

P0586 A COMPARISON OF THE SINGLE-DOSE PHARMACOKINETICS AND SAFETY OF SAXAGLIPTIN IN SUBJECTS WITH HEPATIC IMPAIRMENT AND IN HEALTHY SUBJECTS

2009 ◽  
Vol 20 ◽  
pp. S194
Author(s):  
David W Boulton ◽  
Angela Tang ◽  
Chirag Patel ◽  
Lorna Castaneda ◽  
Uli Frevert ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Healthy Subjects

Sa1031 Mild to Moderate Hepatic Impairment Has No Effect on the Single Dose Pharmacokinetics of Alisporivir (ALV)

2013 ◽  
Vol 144 (5) ◽  
pp. S-977
Author(s):  
Steven J. Kovacs ◽  
June Ke ◽  
Jens Praestgaard ◽  
Avantika Barve ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Moderate Hepatic Impairment
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