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A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects
INTRODUCTION: Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects. METHODS: In this single-center, double-blind, parallel-...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910468/ https://www.ncbi.nlm.nih.gov/pubmed/29536338 http://dx.doi.org/10.1007/s12325-018-0677-1 |
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author | Ikushima, Ippei Jensen, Lene Flint, Anne Nishida, Tomoyuki Zacho, Jeppe Irie, Shin |
author_facet | Ikushima, Ippei Jensen, Lene Flint, Anne Nishida, Tomoyuki Zacho, Jeppe Irie, Shin |
author_sort | Ikushima, Ippei |
collection | PubMed |
description | INTRODUCTION: Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects. METHODS: In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC(0–168h))]. RESULTS: Steady-state exposure of semaglutide was similar for both populations: AUC(0–168h) estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C(max)) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC(0–168h) ERR 1.11; C(max) ERR 1.14). Dose-dependent increases in AUC(0–168h) and C(max) occurred in both populations. Accumulation was as expected, based on the half-life (t(1/2), ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified. CONCLUSIONS: The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects. FUNDING: Novo Nordisk A/S, Denmark. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-018-0677-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5910468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-59104682018-04-24 A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects Ikushima, Ippei Jensen, Lene Flint, Anne Nishida, Tomoyuki Zacho, Jeppe Irie, Shin Adv Ther Original Research INTRODUCTION: Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects. METHODS: In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC(0–168h))]. RESULTS: Steady-state exposure of semaglutide was similar for both populations: AUC(0–168h) estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C(max)) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC(0–168h) ERR 1.11; C(max) ERR 1.14). Dose-dependent increases in AUC(0–168h) and C(max) occurred in both populations. Accumulation was as expected, based on the half-life (t(1/2), ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified. CONCLUSIONS: The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects. FUNDING: Novo Nordisk A/S, Denmark. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-018-0677-1) contains supplementary material, which is available to authorized users. Springer Healthcare 2018-03-13 2018 /pmc/articles/PMC5910468/ /pubmed/29536338 http://dx.doi.org/10.1007/s12325-018-0677-1 Text en © The Author(s) 2018 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Ikushima, Ippei Jensen, Lene Flint, Anne Nishida, Tomoyuki Zacho, Jeppe Irie, Shin A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects |
title | A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects |
title_full | A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects |
title_fullStr | A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects |
title_full_unstemmed | A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects |
title_short | A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects |
title_sort | randomized trial investigating the pharmacokinetics, pharmacodynamics, and safety of subcutaneous semaglutide once-weekly in healthy male japanese and caucasian subjects |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910468/ https://www.ncbi.nlm.nih.gov/pubmed/29536338 http://dx.doi.org/10.1007/s12325-018-0677-1 |
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