PMID- 36415122
OWN - NLM
STAT- MEDLINE
DCOM- 20230202
LR  - 20230227
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 12
IP  - 2
DP  - 2023 Feb
TI  - Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy 
      Chinese Adult Participants.
PG  - 175-180
LID - 10.1002/cpdd.1197 [doi]
AB  - JNJ-73763989, composed of the 2 short-interfering RNA triggers JNJ-73763976 and 
      JNJ-73763924, targets all hepatitis B virus messenger RNAs, thereby reducing all 
      viral proteins. In this phase 1, single-site, open-label, parallel-group, 
      randomized study, participants were given 1 subcutaneous injection of 
      JNJ-73763989 (100 or 200 mg) to investigate the pharmacokinetics, safety, and 
      tolerability of JNJ-73763989 in healthy Chinese adult participants. Plasma and 
      urine pharmacokinetic parameters were determined for each trigger up to 48 hours 
      after dosing. Eighteen participants, 9 per dose group, were enrolled. The median 
      age and weight were 33.0 years and 73.65 kg; 83.3% were male. Exposure of both 
      triggers increased dose proportionally. Median time to maximum concentration 
      ranged from 6.0 to 10.0 hours, and mean elimination half-life ranged from 4.5 to 
      4.8 hours across both triggers and doses. Mean urinary excretion for JNJ-73763976 
      and JNJ-73763924 ranged from 17.7% to 19.4% and 13.1% to 13.2% for the 100- and 
      200-mg dose groups, respectively. All treatment-emergent adverse events (AEs) 
      were mild and resolved by study end, and no AEs or serious AEs resulted in 
      premature study discontinuation or death. Overall, the pharmacokinetics of 
      JNJ-73763989 in healthy Chinese participants were consistent with previous 
      studies, and JNJ-73763989 was generally safe and well tolerated after a single 
      dose.
CI  - (c) 2022, The American College of Clinical Pharmacology.
FAU - Li, Haiyan
AU  - Li H
AD  - Department of Cardiology and Institute of Vascular Medicine, Peking University 
      Third Hospital, Beijing, China.
AD  - Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
FAU - Niu, Xiaoye
AU  - Niu X
AD  - Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Phase I Unit of Drug Clinical Trial Center, Tianjin Fifth Central Hospital, 
      Tianjin, China.
FAU - Zhang, Danning
AU  - Zhang D
AD  - Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
FAU - Zhang, Yanqing
AU  - Zhang Y
AD  - Phase I Unit of Drug Clinical Trial Center, Tianjin Fifth Central Hospital, 
      Tianjin, China.
FAU - Wang, Liqun
AU  - Wang L
AD  - Clinical Pharmacology and Pharmacometrics, Janssen China Research & Development, 
      Beijing, China.
FAU - Miao, Yongqing
AU  - Miao Y
AD  - Clinical Development, Janssen China Research & Development, Beijing, China.
FAU - Jiang, Yanxin
AU  - Jiang Y
AD  - Janssen China Research & Development, Shanghai, China.
FAU - Ji, Jia
AU  - Ji J
AD  - Clinical Pharmacology and Pharmacometrics, Janssen China Research & Development, 
      Beijing, China.
FAU - Chen, Qiaoqiao
AU  - Chen Q
AD  - Clinical Development, Janssen China Research & Development, Beijing, China.
FAU - Wu, Xiaoyun
AU  - Wu X
AD  - Janssen China Research & Development, Shanghai, China.
FAU - Ediage, Emmanuel Njumbe
AU  - Ediage EN
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Kakuda, Thomas N
AU  - Kakuda TN
AD  - Janssen Research & Development, South San Francisco, California, USA.
FAU - Biermer, Michael
AU  - Biermer M
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT04586439
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221122
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Male
MH  - Female
MH  - RNA, Small Interfering
MH  - *East Asian People
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Area Under Curve
OTO - NOTNLM
OT  - Chinese
OT  - JNJ-3989
OT  - JNJ-73763989
OT  - hepatitis B
OT  - pharmacokinetics
OT  - siRNA
OT  - viral hepatitis
EDAT- 2022/11/24 06:00
MHDA- 2023/02/03 06:00
CRDT- 2022/11/23 01:23
PHST- 2022/07/08 00:00 [received]
PHST- 2022/10/04 00:00 [accepted]
PHST- 2022/11/24 06:00 [pubmed]
PHST- 2023/02/03 06:00 [medline]
PHST- 2022/11/23 01:23 [entrez]
AID - 10.1002/cpdd.1197 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2023 Feb;12(2):175-180. doi: 10.1002/cpdd.1197. Epub 
      2022 Nov 22.