Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region.

التفاصيل البيبلوغرافية
العنوان:	Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region.
المؤلفون:	Han K; GSK, Collegeville, Pennsylvania, USA., Ito H; GSK K.K., Tokyo, Japan., Elston R; GSK, Stevenage, United Kingdom., Cremer J; GSK, Durham, North Carolina, USA., Hood S; GSK, Stevenage, United Kingdom., Paff M; GSK, Collegeville, Pennsylvania, USA., Theodore D; GSK, Durham, North Carolina, USA.
المصدر:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 Jan 24; Vol. 67 (1), pp. e0090022. Date of Electronic Publication: 2022 Dec 12.
نوع المنشور:	Randomized Controlled Trial; Multicenter Study; Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, American Society for Microbiology
مواضيع طبية MeSH:	Oligonucleotides, Antisense/therapeutic use , Hepatitis B, Chronic/drug therapy, Humans ; Area Under Curve ; China ; Hong Kong ; Double-Blind Method
مستخلص:	GSK3389404, an N-acetyl galactosamine-conjugated antisense oligonucleotide (ASO), was in clinical development for chronic hepatitis B (CHB) treatment. Few studies have examined ASOs in Asian participants. In this analysis, the plasma pharmacokinetics (PK) of GSK3389404 were characterized and compared in patients with CHB across the Asia-Pacific region (N = 64), including mainland China ( n = 16), Hong Kong ( n = 8), Japan ( n = 21), South Korea ( n = 12), Singapore ( n = 4), and the Philippines ( n = 3), from a phase 2a, multicenter, randomized, double-blind, placebo-controlled study (NCT03020745). Hepatitis B(e) antigen-positive and -negative patients (on or not on stable nucleos[t]ide regimens) received single (30 mg or 120 mg) or multiple (30 mg, 60 mg, or 120 mg weekly or 120 mg biweekly) subcutaneous GSK3389404 injections. The plasma concentrations were measured on day 1 in all cohorts as well as on days 29 and 57 in the multiple-dose cohorts. The GSK3389404 plasma PK were similar to those reported in a previous study in non-Asian healthy participants with a median time to peak concentration (t max ) of 1 to 4 h postdose, a mean half-life of 3 to 5 h across cohorts, and no accumulation following repeat dosing. The GSK3389404 plasma t max and half-life values were dose-independent. The increase in the plasma peak concentration (C max ) and the area under the concentration versus time curve (AUC) was dose-proportional from 60 to 120 mg and greater than dose-proportional from 30 to 60 or 120 mg. The GSK3389404 plasma concentration versus time profiles, half-life, t max , C max , and AUC values were all comparable across the Asia-Pacific populations. Given the similarity of the PK among ASOs, this analysis suggests that the PK from any Asia-Pacific population may be used to guide ASO dose selection in the Asia-Pacific region.
References:	Nucleic Acid Ther. 2019 Feb;29(1):16-32. (PMID: 30570431) Adv Drug Deliv Rev. 2015 Jun 29;87:46-51. (PMID: 25666165) Nucleic Acid Ther. 2016 Apr;26(2):111-7. (PMID: 26959999) Nat Med. 2021 Oct;27(10):1725-1734. (PMID: 34642494) Perspect Clin Res. 2011 Oct;2(4):121-3. (PMID: 22145121) Ther Innov Regul Sci. 2014 May;48(3):393-403. (PMID: 30235544) J Clin Med. 2020 Oct 01;9(10):. (PMID: 33019573) Drug Discov Today. 2020 Mar;25(3):491-496. (PMID: 31926136) Lancet. 2016 Nov 5;388(10057):2239-2253. (PMID: 27665230) Mol Ther Nucleic Acids. 2017 Mar 17;6:116-132. (PMID: 28325278) Drug Metab Dispos. 2003 Nov;31(11):1419-28. (PMID: 14570775) J Hepatol. 2017 Aug;67(2):370-398. (PMID: 28427875) Clin Pharmacol Drug Dev. 2022 Oct;11(10):1191-1202. (PMID: 35971951) Clin Pharmacol Ther. 2008 Sep;84(3):347-61. (PMID: 18231117) Nucleic Acids Res. 2014 Jul;42(13):8796-807. (PMID: 24992960) Expert Opin Drug Metab Toxicol. 2009 Apr;5(4):381-91. (PMID: 19379126) BMC Infect Dis. 2019 Sep 18;19(1):811. (PMID: 31533643) Clin Pharmacol Drug Dev. 2019 Aug;8(6):790-801. (PMID: 30861337) J Hepatol. 2022 Oct;77(4):967-977. (PMID: 35714812) Nucleic Acid Ther. 2019 Apr;29(2):82-91. (PMID: 30817230)
فهرسة مساهمة:	Keywords: Asia-Pacific; GSK3389404; antisense oligonucleotide; chronic hepatitis B virus infection; pharmacokinetics
المشرفين على المادة:	0 (Oligonucleotides, Antisense)
تواريخ الأحداث:	Date Created: 20221212 Date Completed: 20230126 Latest Revision: 20230202
رمز التحديث:	20240829
مُعرف محوري في PubMed:	PMC9872700
DOI:	10.1128/aac.00900-22
PMID:	36507675
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1098-6596
DOI:	10.1128/aac.00900-22