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Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects
INTRODUCTION: Ultra rapid lispro (URLi) is a novel insulin lispro formulation that was developed to more closely match physiological insulin secretion. The aims of this study were to demonstrate the bioequivalence (BE) of a concentrated formulation (U200) of URLi to the U100 formulation of URLi afte...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Healthcare
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376802/ https://www.ncbi.nlm.nih.gov/pubmed/32535742 http://dx.doi.org/10.1007/s13300-020-00848-4 |
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author | Linnebjerg, Helle LaBell, Elizabeth Smith Dellva, Mary Anne Coutant, David E. Leohr, Jennifer |
author_facet | Linnebjerg, Helle LaBell, Elizabeth Smith Dellva, Mary Anne Coutant, David E. Leohr, Jennifer |
author_sort | Linnebjerg, Helle |
collection | PubMed |
description | INTRODUCTION: Ultra rapid lispro (URLi) is a novel insulin lispro formulation that was developed to more closely match physiological insulin secretion. The aims of this study were to demonstrate the bioequivalence (BE) of a concentrated formulation (U200) of URLi to the U100 formulation of URLi after subcutaneous (SC) administration and to evaluate the glucodynamics (GD) of these formulations. METHODS: This phase 1, randomized, two‐sequence, four‐period, double-blind, replicate crossover study was conducted in 68 healthy subjects. At each dosing visit, subjects received a 15-U SC dose of either U100 URLi or U200 URLi followed by a 10-h euglycemic clamp procedure. Serum insulin lispro and blood glucose concentrations were measured, and the glucose infusion rate was continuously adjusted during the clamp to maintain the target blood glucose. RESULTS: Bioequivalence of U200 URLi relative to U100 URLi was demonstrated. The 90% confidence intervals (CIs) of the ratios of geometric least squares (LS) means for the maximum insulin concentration and total exposure were within the BE limits of 0.80–1.25. Additionally, the 90% CIs for the ratios of geometric LS means for maximum glucose infusion rate and total glucose infused were within the BE limits. The early 50% t(max) occurred at approximately the same time for the U100 and U200 URLi formulations, and the insulin exposure within the first 15 min was similar for both formulations. The tolerability of the two URLi formulations was comparable. CONCLUSIONS: This study demonstrated that the U100 and U200 URLi formulations are bioequivalent. The accelerated insulin absorption observed for the U100 formulation was maintained with the U200 URLi formulation. Further, the GD were similar for both formulations, supporting the ability of individuals to transfer from U100 to U200 URLi in a 1:1 unit conversion. TRIAL REGISTRATION: NCT03616977. |
format | Online Article Text |
id | pubmed-7376802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-73768022020-07-27 Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects Linnebjerg, Helle LaBell, Elizabeth Smith Dellva, Mary Anne Coutant, David E. Leohr, Jennifer Diabetes Ther Original Research INTRODUCTION: Ultra rapid lispro (URLi) is a novel insulin lispro formulation that was developed to more closely match physiological insulin secretion. The aims of this study were to demonstrate the bioequivalence (BE) of a concentrated formulation (U200) of URLi to the U100 formulation of URLi after subcutaneous (SC) administration and to evaluate the glucodynamics (GD) of these formulations. METHODS: This phase 1, randomized, two‐sequence, four‐period, double-blind, replicate crossover study was conducted in 68 healthy subjects. At each dosing visit, subjects received a 15-U SC dose of either U100 URLi or U200 URLi followed by a 10-h euglycemic clamp procedure. Serum insulin lispro and blood glucose concentrations were measured, and the glucose infusion rate was continuously adjusted during the clamp to maintain the target blood glucose. RESULTS: Bioequivalence of U200 URLi relative to U100 URLi was demonstrated. The 90% confidence intervals (CIs) of the ratios of geometric least squares (LS) means for the maximum insulin concentration and total exposure were within the BE limits of 0.80–1.25. Additionally, the 90% CIs for the ratios of geometric LS means for maximum glucose infusion rate and total glucose infused were within the BE limits. The early 50% t(max) occurred at approximately the same time for the U100 and U200 URLi formulations, and the insulin exposure within the first 15 min was similar for both formulations. The tolerability of the two URLi formulations was comparable. CONCLUSIONS: This study demonstrated that the U100 and U200 URLi formulations are bioequivalent. The accelerated insulin absorption observed for the U100 formulation was maintained with the U200 URLi formulation. Further, the GD were similar for both formulations, supporting the ability of individuals to transfer from U100 to U200 URLi in a 1:1 unit conversion. TRIAL REGISTRATION: NCT03616977. Springer Healthcare 2020-06-13 2020-08 /pmc/articles/PMC7376802/ /pubmed/32535742 http://dx.doi.org/10.1007/s13300-020-00848-4 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Linnebjerg, Helle LaBell, Elizabeth Smith Dellva, Mary Anne Coutant, David E. Leohr, Jennifer Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects |
title | Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects |
title_full | Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects |
title_fullStr | Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects |
title_full_unstemmed | Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects |
title_short | Bioequivalence of Ultra Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects |
title_sort | bioequivalence of ultra rapid lispro (urli) u100 and u200 formulations in healthy subjects |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376802/ https://www.ncbi.nlm.nih.gov/pubmed/32535742 http://dx.doi.org/10.1007/s13300-020-00848-4 |
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