Pharmacokinetics, Safety and Tolerability of JNJ-56136379, a Novel Hepatitis B Virus Capsid Assembly Modulator, in Healthy Subjects.
Adv Ther
; 36(9): 2450-2462, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31267367
ABSTRACT
INTRODUCTION:
Hepatitis B viral capsid assembly is an attractive target for new antiviral treatments. JNJ-56136379 (JNJ-6379) is a potent capsid assembly modulator in vitro with a dual mode of action. In Part 1 of this first-in-human study in healthy adults, the pharmacokinetics (PK), safety and tolerability of JNJ-6379 were evaluated following single ascending and multiple oral doses.METHODS:
This was a double-blind, randomized, placebo-controlled study in 30 healthy adults. Eighteen subjects were randomized to receive single doses of JNJ-6379 (25 to 600 mg) or placebo. Twelve subjects were randomized to receive 150 mg JNJ-6379 or placebo twice daily for 2 days, followed by 100 mg JNJ-6379 or placebo daily for 10 days.RESULTS:
The maximum observed plasma concentration and the area under the curve increased dose proportionally from 25 to 300 mg JNJ-6379. Following multiple dosing, steady-state conditions were achieved on day 8. Steady-state clearance was similar following single and multiple dosing, suggesting time-linear PK. All adverse events (AEs) reported were mild to moderate in severity. There were no serious AEs or dose-limiting toxicities and no apparent relationship to dose for any AE.CONCLUSION:
JNJ-6379 was well tolerated in this study. Based on the safety profile and plasma exposures of JNJ-6379 in healthy subjects, a dosing regimen was selected for Part 2 of this study in patients with chronic hepatitis B. This is anticipated to achieve trough plasma exposures of JNJ-6379 at steady state of more than three times the 90% effective concentration of viral replication determined in vitro. TRIAL REGISTRATION Clinicaltrials.gov identifier, NCT02662712.FUNDING:
Janssen Pharmaceutica.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Piperidinas
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Azepinas
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Capsídeo
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Hepatite B Crônica
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Adv Ther
Ano de publicação:
2019
Tipo de documento:
Article