PMID- 31267367
OWN - NLM
STAT- MEDLINE
DCOM- 20200610
LR  - 20200610
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Linking)
VI  - 36
IP  - 9
DP  - 2019 Sep
TI  - Pharmacokinetics, Safety and Tolerability of JNJ-56136379, a Novel Hepatitis B 
      Virus Capsid Assembly Modulator, in Healthy Subjects.
PG  - 2450-2462
LID - 10.1007/s12325-019-01017-1 [doi]
AB  - 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.
FAU - Vandenbossche, Joris
AU  - Vandenbossche J
AD  - Janssen Pharmaceutica NV, Beerse, Belgium. jvdbossc@its.jnj.com.
FAU - Jessner, Wolfgang
AU  - Jessner W
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - van den Boer, Maarten
AU  - van den Boer M
AD  - Janssen Pharmaceutica NV, Merksem, Belgium.
FAU - Biewenga, Jeike
AU  - Biewenga J
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Berke, Jan Martin
AU  - Berke JM
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Talloen, Willem
AU  - Talloen W
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - De Zwart, Loeckie
AU  - De Zwart L
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Snoeys, Jan
AU  - Snoeys J
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Yogaratnam, Jeysen
AU  - Yogaratnam J
AD  - Janssen Biopharma, Inc., South San Francisco, CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02662712
SI  - figshare/10.6084/m9.figshare.8256479
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190702
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Antiviral Agents)
RN  - 0 (Azepines)
RN  - 0 (JNJ-38893777)
RN  - 0 (Piperidines)
EIN - Adv Ther. 2020 Mar 4;:. PMID: 32133584
MH  - Adult
MH  - Antiviral Agents/*administration & dosage
MH  - Area Under Curve
MH  - Azepines/administration & dosage/adverse effects/*pharmacology
MH  - Capsid/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Healthy Volunteers
MH  - Hepatitis B virus/drug effects
MH  - Hepatitis B, Chronic/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperidines/administration & dosage/adverse effects/*pharmacology
OTO - NOTNLM
OT  - Antiviral activity
OT  - Capsid assembly
OT  - Hepatitis B virus
OT  - Infectious diseases
OT  - Phase 1
EDAT- 2019/07/04 06:00
MHDA- 2020/06/11 06:00
CRDT- 2019/07/04 06:00
PHST- 2019/04/15 00:00 [received]
PHST- 2019/07/04 06:00 [pubmed]
PHST- 2020/06/11 06:00 [medline]
PHST- 2019/07/04 06:00 [entrez]
AID - 10.1007/s12325-019-01017-1 [pii]
AID - 10.1007/s12325-019-01017-1 [doi]
PST - ppublish
SO  - Adv Ther. 2019 Sep;36(9):2450-2462. doi: 10.1007/s12325-019-01017-1. Epub 2019 
      Jul 2.