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Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis
Risankizumab, a humanized monoclonal antibody that targets interleukin‐23 p19 subunit, was developed for the treatment of psoriasis. This work characterizes risankizumab pharmacokinetics in Japanese and Chinese healthy subjects compared with white healthy subjects and in Japanese patients with moder...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852105/ https://www.ncbi.nlm.nih.gov/pubmed/31257614 http://dx.doi.org/10.1002/jcph.1473 |
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author | Khatri, Amit Eckert, Doerthe Oberoi, Rajneet Suleiman, Ahmed Pang, Yinuo Cheng, Ling Othman, Ahmed A. |
author_facet | Khatri, Amit Eckert, Doerthe Oberoi, Rajneet Suleiman, Ahmed Pang, Yinuo Cheng, Ling Othman, Ahmed A. |
author_sort | Khatri, Amit |
collection | PubMed |
description | Risankizumab, a humanized monoclonal antibody that targets interleukin‐23 p19 subunit, was developed for the treatment of psoriasis. This work characterizes risankizumab pharmacokinetics in Japanese and Chinese healthy subjects compared with white healthy subjects and in Japanese patients with moderate to severe plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis. A phase 1, single‐dose study evaluated risankizumab pharmacokinetics and safety/tolerability in healthy white (18 and 300 mg subcutaneous [SC]), Japanese (18, 90, and 300 mg SC and 200, 600, and 1200 mg intravenous [IV]), and Chinese (18, 90, and 300 mg SC) subjects; pharmacokinetic data were analyzed using noncompartmental methods. Risankizumab pharmacokinetic data from phase 2/3 studies in Japanese patients with plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis following multiple SC doses of 75 mg or 150 mg were analyzed using a population pharmacokinetic approach along with data from the phase 1 and global phase 1 to 3 studies. Risankizumab plasma exposures (peak plasma concentration and area under the concentration‐time curve) were approximately dose‐proportional across 18‐ to 300‐mg SC or 200‐ to 1200‐mg IV doses. Risankizumab terminal elimination half‐life (harmonic mean 27–34 days) was comparable across doses and ethnicities. Risankizumab exposures were approximately 20% to 30% higher in Japanese and Chinese healthy subjects compared with white healthy subjects or in Japanese patients compared with non‐Japanese patients. After accounting for body‐weight differences, risankizumab exposures were comparable across ethnicities. Overall, there was no ethnic impact on risankizumab pharmacokinetics, and the small difference in exposure due to body weight has no clinical relevance. |
format | Online Article Text |
id | pubmed-6852105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68521052019-11-22 Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis Khatri, Amit Eckert, Doerthe Oberoi, Rajneet Suleiman, Ahmed Pang, Yinuo Cheng, Ling Othman, Ahmed A. J Clin Pharmacol Pharmacokinetics Risankizumab, a humanized monoclonal antibody that targets interleukin‐23 p19 subunit, was developed for the treatment of psoriasis. This work characterizes risankizumab pharmacokinetics in Japanese and Chinese healthy subjects compared with white healthy subjects and in Japanese patients with moderate to severe plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis. A phase 1, single‐dose study evaluated risankizumab pharmacokinetics and safety/tolerability in healthy white (18 and 300 mg subcutaneous [SC]), Japanese (18, 90, and 300 mg SC and 200, 600, and 1200 mg intravenous [IV]), and Chinese (18, 90, and 300 mg SC) subjects; pharmacokinetic data were analyzed using noncompartmental methods. Risankizumab pharmacokinetic data from phase 2/3 studies in Japanese patients with plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis following multiple SC doses of 75 mg or 150 mg were analyzed using a population pharmacokinetic approach along with data from the phase 1 and global phase 1 to 3 studies. Risankizumab plasma exposures (peak plasma concentration and area under the concentration‐time curve) were approximately dose‐proportional across 18‐ to 300‐mg SC or 200‐ to 1200‐mg IV doses. Risankizumab terminal elimination half‐life (harmonic mean 27–34 days) was comparable across doses and ethnicities. Risankizumab exposures were approximately 20% to 30% higher in Japanese and Chinese healthy subjects compared with white healthy subjects or in Japanese patients compared with non‐Japanese patients. After accounting for body‐weight differences, risankizumab exposures were comparable across ethnicities. Overall, there was no ethnic impact on risankizumab pharmacokinetics, and the small difference in exposure due to body weight has no clinical relevance. John Wiley and Sons Inc. 2019-06-30 2019-12 /pmc/articles/PMC6852105/ /pubmed/31257614 http://dx.doi.org/10.1002/jcph.1473 Text en © 2019 AbbVie Inc. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Pharmacokinetics Khatri, Amit Eckert, Doerthe Oberoi, Rajneet Suleiman, Ahmed Pang, Yinuo Cheng, Ling Othman, Ahmed A. Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis |
title | Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis |
title_full | Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis |
title_fullStr | Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis |
title_full_unstemmed | Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis |
title_short | Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis |
title_sort | pharmacokinetics of risankizumab in asian healthy subjects and patients with moderate to severe plaque psoriasis, generalized pustular psoriasis, and erythrodermic psoriasis |
topic | Pharmacokinetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852105/ https://www.ncbi.nlm.nih.gov/pubmed/31257614 http://dx.doi.org/10.1002/jcph.1473 |
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