Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hsu, Cheng‐Pang, Maddox, Judy, Block, Geoffrey, Bartley, Yessenia, Yu, Zhigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
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
_version_ 1784804238267777024
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
work_keys_str_mv AT hsuchengpang influenceofrenalfunctiononpharmacokineticspharmacodynamicsandsafetyofasingledoseofromosozumab
AT maddoxjudy influenceofrenalfunctiononpharmacokineticspharmacodynamicsandsafetyofasingledoseofromosozumab
AT blockgeoffrey influenceofrenalfunctiononpharmacokineticspharmacodynamicsandsafetyofasingledoseofromosozumab
AT bartleyyessenia influenceofrenalfunctiononpharmacokineticspharmacodynamicsandsafetyofasingledoseofromosozumab
AT yuzhigang influenceofrenalfunctiononpharmacokineticspharmacodynamicsandsafetyofasingledoseofromosozumab