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Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab
We evaluated the pharmacokinetics, pharmacodynamics, and safety of a single subcutaneous dose of romosozumab 210 mg, a monoclonal antibody against sclerostin, in an open‐label, parallel‐group study in participants with severe (stage 4) renal impairment (RI; n = 8) or end‐stage renal disease requirin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542825/ https://www.ncbi.nlm.nih.gov/pubmed/35304747 http://dx.doi.org/10.1002/jcph.2050 |
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author | Hsu, Cheng‐Pang Maddox, Judy Block, Geoffrey Bartley, Yessenia Yu, Zhigang |
author_facet | Hsu, Cheng‐Pang Maddox, Judy Block, Geoffrey Bartley, Yessenia Yu, Zhigang |
author_sort | Hsu, Cheng‐Pang |
collection | PubMed |
description | We evaluated the pharmacokinetics, pharmacodynamics, and safety of a single subcutaneous dose of romosozumab 210 mg, a monoclonal antibody against sclerostin, in an open‐label, parallel‐group study in participants with severe (stage 4) renal impairment (RI; n = 8) or end‐stage renal disease requiring hemodialysis (ESRD‐RH; n = 8), or healthy participants with normal renal function (n = 8). Compared with the group with normal renal function, the mean romosozumab exposure was 31% and 43% higher as measured by maximum observed serum concentration and area under the concentration‐time curve, respectively, in the severe RI group and similar to those in the ESRD‐RH group. For all 3 groups, the maximum mean percent increase in procollagen type 1 N terminal propeptide and decrease in serum C‐telopeptide levels from baseline were observed on day 15. Changes in procollagen type 1 N terminal propeptide and serum C‐telopeptide were of similar patterns in all 3 groups. The single dose of romosozumab 210 mg was well tolerated. Adverse events (AEs) were reported for 13 patients (7 patients with severe RI and 6 with ESRD‐RH), with no deaths, AEs, or serious AEs leading to withdrawal. The incidence of subjects with postbaseline transient decreases in serum calcium (severe RI, n = 1; ESRD‐RH, n = 5) and increases in intact parathyroid hormone (severe RI, n = 7; ESRD‐RH, n = 7; healthy, n = 3) were greater in severe RI and ESRD‐RH groups than in the healthy group. All reported events of hypocalcemia (severe RI, n = 1; ESRD‐RH, n = 4) were asymptomatic. These results support the use of romosozumab without dose adjustment in patients with severe RI or ESRD‐RH. |
format | Online Article Text |
id | pubmed-9542825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95428252022-10-14 Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab Hsu, Cheng‐Pang Maddox, Judy Block, Geoffrey Bartley, Yessenia Yu, Zhigang J Clin Pharmacol Special Populations We evaluated the pharmacokinetics, pharmacodynamics, and safety of a single subcutaneous dose of romosozumab 210 mg, a monoclonal antibody against sclerostin, in an open‐label, parallel‐group study in participants with severe (stage 4) renal impairment (RI; n = 8) or end‐stage renal disease requiring hemodialysis (ESRD‐RH; n = 8), or healthy participants with normal renal function (n = 8). Compared with the group with normal renal function, the mean romosozumab exposure was 31% and 43% higher as measured by maximum observed serum concentration and area under the concentration‐time curve, respectively, in the severe RI group and similar to those in the ESRD‐RH group. For all 3 groups, the maximum mean percent increase in procollagen type 1 N terminal propeptide and decrease in serum C‐telopeptide levels from baseline were observed on day 15. Changes in procollagen type 1 N terminal propeptide and serum C‐telopeptide were of similar patterns in all 3 groups. The single dose of romosozumab 210 mg was well tolerated. Adverse events (AEs) were reported for 13 patients (7 patients with severe RI and 6 with ESRD‐RH), with no deaths, AEs, or serious AEs leading to withdrawal. The incidence of subjects with postbaseline transient decreases in serum calcium (severe RI, n = 1; ESRD‐RH, n = 5) and increases in intact parathyroid hormone (severe RI, n = 7; ESRD‐RH, n = 7; healthy, n = 3) were greater in severe RI and ESRD‐RH groups than in the healthy group. All reported events of hypocalcemia (severe RI, n = 1; ESRD‐RH, n = 4) were asymptomatic. These results support the use of romosozumab without dose adjustment in patients with severe RI or ESRD‐RH. John Wiley and Sons Inc. 2022-04-02 2022-09 /pmc/articles/PMC9542825/ /pubmed/35304747 http://dx.doi.org/10.1002/jcph.2050 Text en © 2022 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://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 | Special Populations Hsu, Cheng‐Pang Maddox, Judy Block, Geoffrey Bartley, Yessenia Yu, Zhigang Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab |
title | Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab |
title_full | Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab |
title_fullStr | Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab |
title_full_unstemmed | Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab |
title_short | Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab |
title_sort | influence of renal function on pharmacokinetics, pharmacodynamics, and safety of a single dose of romosozumab |
topic | Special Populations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542825/ https://www.ncbi.nlm.nih.gov/pubmed/35304747 http://dx.doi.org/10.1002/jcph.2050 |
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