PMID- 35262846
OWN - NLM
STAT- MEDLINE
DCOM- 20220706
LR  - 20230803
IS  - 1179-1926 (Electronic)
IS  - 0312-5963 (Print)
IS  - 0312-5963 (Linking)
VI  - 61
IP  - 6
DP  - 2022 Jun
TI  - Single-Dose Pharmacokinetics of Milvexian in Participants with Mild or Moderate 
      Hepatic Impairment Compared with Healthy Participants.
PG  - 857-867
LID - 10.1007/s40262-022-01110-9 [doi]
AB  - BACKGROUND: Patients with hepatic impairment receiving antithrombotic agents 
      metabolized primarily through the liver can be at risk for bleeding. Milvexian 
      (BMS-986177/JNJ-70033093) is a small-molecule, active-site inhibitor of activated 
      Factor XI (FXIa). Modulation of FXI may provide systemic anticoagulation without 
      increased risk of clinically significant bleeding. OBJECTIVE: This open-label 
      study evaluated the effects of mild or moderate hepatic impairment on the 
      pharmacokinetics of milvexian to assess their impact on safety and dosing. 
      METHODS: Single doses of milvexian 60 mg were administered to participants with 
      mild hepatic impairment (n = 9), moderate hepatic impairment (n = 8), and normal 
      hepatic function (n = 9). Healthy participants were matched to participants with 
      hepatic impairment by body weight, age, and sex. Analysis of variance was 
      performed on natural log-transformed milvexian exposure parameters, with hepatic 
      function group as a fixed effect. RESULTS: Single doses of milvexian 60 mg were 
      generally well tolerated, with no serious adverse events (AEs), bleeding AEs, or 
      discontinuations due to AEs. Geometric mean ratios (90% confidence interval) for 
      total milvexian maximum observed plasma concentration and area under the plasma 
      concentration-time curve from time zero extrapolated to infinite time were 1.180 
      (0.735-1.895) and 1.168 (0.725-1.882), respectively, for mild hepatic impairment 
      versus normal hepatic function and 1.140 (0.699-1.857) and 0.996 (0.609-1.628), 
      respectively, for moderate hepatic impairment versus normal hepatic function. 
      Across groups, milvexian exposure-related increases were observed for activated 
      partial thromboplastin time. CONCLUSION: Milvexian was well tolerated in 
      participants with normal, mildly impaired, and moderately impaired hepatic 
      function. Observed pharmacokinetic changes suggest it is unlikely that dose 
      adjustments will be necessary in patients with mild or moderate hepatic 
      impairment. Clinical Trial RegistrationClinicaltrials.gov identifier: 
      NCT02982707.
CI  - (c) 2022. The Author(s).
FAU - Perera, Vidya
AU  - Perera V
AUID- ORCID: 0000-0002-9055-0123
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA. Vidya.Perera@bms.com.
FAU - Abelian, Grigor
AU  - Abelian G
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
FAU - Li, Danshi
AU  - Li D
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
FAU - Wang, Zhaoqing
AU  - Wang Z
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
FAU - Zhang, Liping
AU  - Zhang L
AD  - Global Clinical Pharmacology, Janssen Research & Development, LLC, Raritan, NJ, 
      USA.
FAU - Lubin, Susan
AU  - Lubin S
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
FAU - Chen, Wei
AU  - Chen W
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
FAU - Bello, Akintunde
AU  - Bello A
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
FAU - Murthy, Bindu
AU  - Murthy B
AD  - Early Clinical and Translational Research, Bristol Myers Squibb, Princeton, NJ, 
      USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02982707
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220309
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (Fibrinolytic Agents)
SB  - IM
MH  - Area Under Curve
MH  - *Fibrinolytic Agents/therapeutic use
MH  - Healthy Volunteers
MH  - Humans
MH  - *Liver Diseases
PMC - PMC9249726
COIS- VP, GA, DL, ZW, SL, WC, AB, and BM are full-time employees of Bristol Myers 
      Squibb. LZ is a full-time employee of Janssen Research & Development, LLC.
EDAT- 2022/03/10 06:00
MHDA- 2022/07/07 06:00
PMCR- 2022/03/09
CRDT- 2022/03/09 12:34
PHST- 2022/02/01 00:00 [accepted]
PHST- 2022/03/10 06:00 [pubmed]
PHST- 2022/07/07 06:00 [medline]
PHST- 2022/03/09 12:34 [entrez]
PHST- 2022/03/09 00:00 [pmc-release]
AID - 10.1007/s40262-022-01110-9 [pii]
AID - 1110 [pii]
AID - 10.1007/s40262-022-01110-9 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 2022 Jun;61(6):857-867. doi: 10.1007/s40262-022-01110-9. Epub 
      2022 Mar 9.