Pharmacokinetics of JNJ-73763989 and JNJ-56136379 (Bersacapavir) in Participants With Moderate Hepatic Impairment.
clinical pharmacology
hepatic impairment
hepatitis B
viral hepatitis
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
17
11
2022
accepted:
06
02
2023
medline:
12
5
2023
pubmed:
15
2
2023
entrez:
14
2
2023
Statut:
ppublish
Résumé
JNJ-73763989 is comprised of 2 short interfering RNAs (siRNAs), JNJ-73763976 and JNJ-73763924, that target hepatitis B virus (HBV) mRNAs for degradation, thereby inhibiting HBV replication. JNJ-56136379 is a capsid assembly modulator that inhibits HBV replication by inducing the formation of empty capsids (CAM-E). In 2 phase 1, open-label, non-randomized, single-center studies, the single-dose pharmacokinetics, safety, and tolerability of JNJ-73763989 or JNJ-56136379 were assessed in participants with moderate hepatic impairment (Child-Pugh Class B) versus participants with normal liver function. Participants in both studies received a single subcutaneous dose of JNJ-73763989 200 mg or oral JNJ-56136379 250 mg, followed by an evaluation of plasma pharmacokinetic parameters and safety assessments. Plasma exposure to JNJ-73763976, JNJ-73763924, and JNJ-56136379 was 1.3- to 1.4-, 1.8- to 2.2-, and 1.1- to 1.3-fold higher in participants with moderate hepatic impairment versus participants with normal liver function; however, these increases were not considered clinically relevant. Both drugs were well tolerated and safe, with 7 (21.9%) participants experiencing 1 or more treatment-emergent adverse events, 3 of which were related to JNJ-56136379. Overall, the plasma exposures of JNJ-73763989 and JNJ-56136379 were higher in participants with moderate hepatic impairment, but both were well tolerated. Further studies are needed to evaluate the effect of hepatic impairment under multiple-dose administration.
Substances chimiques
JNJ-56136379
0
Antiviral Agents
0
Organic Chemicals
0
Banques de données
ClinicalTrials.gov
['NCT04208386', 'NCT01208399']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
732-741Informations de copyright
© 2023, The American College of Clinical Pharmacology.
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