Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy Chinese Adult Participants
Haiyan Li 1 2 , Xiaoye Niu 2 , Yu Zhang 3 , Danning Zhang 2 , Yanqing Zhang 3 , Liqun Wang 4 , Yongqing Miao 5 , Yanxin Jiang 6 , Jia Ji 4 , Qiaoqiao Chen 5 , Xiaoyun Wu 6 , Emmanuel Njumbe Ediage 7 , Thomas N Kakuda 8 , Michael Biermer 7
Affiliations
Affiliations
1
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
2
Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
3
Phase I Unit of Drug Clinical Trial Center, Tianjin Fifth Central Hospital, Tianjin, China.
4
Clinical Pharmacology and Pharmacometrics, Janssen China Research & Development, Beijing, China.
5
Clinical Development, Janssen China Research & Development, Beijing, China.
6
Janssen China Research & Development, Shanghai, China.
7
Janssen Pharmaceutica NV, Beerse, Belgium.
8
Janssen Research & Development, South San Francisco, California, USA.
PMID: 36415122 DOI: 10.1002/cpdd.1197
Abstract
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.