2. Academic Validation
  3. Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy Chinese Adult Participants

Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy Chinese Adult Participants

  • Clin Pharmacol Drug Dev. 2023 Feb;12(2):175-180. doi: 10.1002/cpdd.1197.
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.

Keywords

Chinese; JNJ-3989; JNJ-73763989; hepatitis B; pharmacokinetics; siRNA; viral hepatitis.

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