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Erschienen in: Advances in Therapy 9/2019

02.07.2019 | Original Research

Pharmacokinetics, Safety and Tolerability of JNJ-56136379, a Novel Hepatitis B Virus Capsid Assembly Modulator, in Healthy Subjects

verfasst von: Joris Vandenbossche, Wolfgang Jessner, Maarten van den Boer, Jeike Biewenga, Jan Martin Berke, Willem Talloen, Loeckie De Zwart, Jan Snoeys, Jeysen Yogaratnam

Erschienen in: Advances in Therapy | Ausgabe 9/2019

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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.
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Metadaten
Titel
Pharmacokinetics, Safety and Tolerability of JNJ-56136379, a Novel Hepatitis B Virus Capsid Assembly Modulator, in Healthy Subjects
verfasst von
Joris Vandenbossche
Wolfgang Jessner
Maarten van den Boer
Jeike Biewenga
Jan Martin Berke
Willem Talloen
Loeckie De Zwart
Jan Snoeys
Jeysen Yogaratnam
Publikationsdatum
02.07.2019
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 9/2019
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-019-01017-1

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