First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis.
Purpose: The purpose of this study is to evaluate the pharmacokinetics, immunogenicity, safety, and tolerability of guselkumab, a human monoclonal antibody with high affinity and specificity for binding to interleukin-23. Methods: In this first-in-human, phase 1, randomized study, a single intraveno...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 72; no. 11; pp. 1303 - 1311 |
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| Autores principales: | , , , , , , , , , |
| Formato: | clinical trial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Nov2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=118671723&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 118671723 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Nov2016 vid: 72 iid: 11 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 118671723 118671723 144077317 118671723 10.1007/s00228-016-2110-5 118671723 ppf: 1303 ppct: 8 formats: fmt: @attributes: type: P tig: atl: First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis. aug: au: Zhuang, Yanli Calderon, Cesar Marciniak, Stanley Bouman-Thio, Esther Szapary, Philippe Yang, Tong-Yuan Schantz, Allen Davis, Hugh Zhou, Honghui Xu, Zhenhua affil: Biologics Clinical Pharmacology , Janssen Research & Development, LLC , 1400 McKean Road Spring House 19477 USA sug: subj: Antibodies, Monoclonal Metabolism Psoriasis Drug Therapy Human Male Female Clinical Trials Interleukins Administration, Intravenous Injections, Subcutaneous Antibodies, Monoclonal Administration and Dosage Antibodies, Monoclonal Therapeutic Use Metabolic Clearance Rate Male Female ab: Purpose: The purpose of this study is to evaluate the pharmacokinetics, immunogenicity, safety, and tolerability of guselkumab, a human monoclonal antibody with high affinity and specificity for binding to interleukin-23. Methods: In this first-in-human, phase 1, randomized study, a single intravenous (IV; 0.03-10 mg/kg) or subcutaneous (SC; 10-300 mg) dose of guselkumab was administered to 47 healthy subjects, and a single SC dose (placebo, 10, 30, 100, 300 mg) was administered to 24 patients with moderate-to-severe psoriasis. Results: Mean maximum observed serum concentration and area under the zero-to-infinity serum concentration-time curve of guselkumab increased in an approximately dose-proportional manner over the dose range of 0.03-10 mg/kg following a single IV administration or 10-300 mg following a single SC administration. Mean clearance and volume of distribution ranged from 3.62-6.03 mL/day/kg and 99.38-123.22 mL/kg, respectively. Mean half-life ranged from 12 to 19 days in healthy subjects and patients with psoriasis. Among guselkumab-treated subjects/patients, 1/30 (3.3 %) healthy subjects in the IV group, 0/6 healthy subjects in the SC group, and 1/20 (5.0 %) patients with psoriasis tested positive for antibodies to guselkumab. No clinically significant adverse events were identified in this study. Conclusion: Guselkumab pharmacokinetic profiles were generally comparable between healthy subjects and patients with psoriasis. Guselkumab, administered as an IV infusion or SC injection, was well tolerated in healthy subjects and patients with psoriasis. pubtype: Academic Journal doctype: clinical trial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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