Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers
INTRODUCTION: Vildagliptin and metformin are two well-established oral antidiabetics with a complementary mechanism of action. Two new generic products, vildagliptin and its fixed-drug combination (FDC) with metformin, were tested for bioequivalence versus the approved originator reference products...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174400/ https://www.ncbi.nlm.nih.gov/pubmed/35543870 http://dx.doi.org/10.1007/s13300-022-01269-1 |
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author | Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Klingberg, Ulrike Vadla, Hari Kiran Chary Prathap, Vamshi Ramana |
author_facet | Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Klingberg, Ulrike Vadla, Hari Kiran Chary Prathap, Vamshi Ramana |
author_sort | Schnaars, Yvonne |
collection | PubMed |
description | INTRODUCTION: Vildagliptin and metformin are two well-established oral antidiabetics with a complementary mechanism of action. Two new generic products, vildagliptin and its fixed-drug combination (FDC) with metformin, were tested for bioequivalence versus the approved originator reference products (Galvus® and Eucreas®). METHODS: Three randomized studies with two-treatment, two-period, two-sequence crossover design were conducted in healthy adults. One study evaluated vildagliptin 50 mg tablets as single dose under fasting conditions. Vildagliptin–metformin FDC tablet strengths of 50/850 mg and 50/1000 mg were evaluated in separate studies as single dose under fed conditions, given 30 min after a standardized high-fat, high-calorie breakfast following 10 h overnight fasting. Blood samples for analysis were collected until 24 h after dosing in each study period. Bioequivalence between test (T) and reference (R) products required 90% confidence interval (CIs) for the geometric least square (LS) mean T/R ratio to be within 80–125% for the pharmacokinetic parameters, maximum plasma concentration (C(max)), and area under the curve (AUC(0–t)). RESULTS: The 90% CIs of geometric LS means of T/R ratio for C(max) and AUC(0–t) with vildagliptin tablets of 50 mg were 92.22–103.94% and 99.00–102.66%, respectively; corresponding results with FDC tablets for 50/850 mg tablets were 94.81–115.41% and 95.28–106.00% for vildagliptin and 90.87–101.18% and 90.56–100.09% for metformin; for 50/1000 mg tablets C(max) and AUC(0–t) were 105.56–122.30% and 98.30–107.55%, respectively, for vildagliptin and 92.14–103.73% and 94.60–101.81%, respectively, for metformin. Other parameters such as AUC(0–∞), time to maximum concentration (T(max)), and terminal half-life (t(1/2)) were comparable between test and reference products. Adverse events (AEs), mainly vomiting, were reported without relevant difference between test and reference products in each study. AEs were generally mild and transient. No severe or serious AEs occurred. CONCLUSIONS: The new generic drug products of vildagliptin and the FDCs of vildagliptin and metformin demonstrated bioequivalence to the approved originator products and are therefore expected to provide similar therapeutic effects. |
format | Online Article Text |
id | pubmed-9174400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-91744002022-06-09 Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Klingberg, Ulrike Vadla, Hari Kiran Chary Prathap, Vamshi Ramana Diabetes Ther Original Research INTRODUCTION: Vildagliptin and metformin are two well-established oral antidiabetics with a complementary mechanism of action. Two new generic products, vildagliptin and its fixed-drug combination (FDC) with metformin, were tested for bioequivalence versus the approved originator reference products (Galvus® and Eucreas®). METHODS: Three randomized studies with two-treatment, two-period, two-sequence crossover design were conducted in healthy adults. One study evaluated vildagliptin 50 mg tablets as single dose under fasting conditions. Vildagliptin–metformin FDC tablet strengths of 50/850 mg and 50/1000 mg were evaluated in separate studies as single dose under fed conditions, given 30 min after a standardized high-fat, high-calorie breakfast following 10 h overnight fasting. Blood samples for analysis were collected until 24 h after dosing in each study period. Bioequivalence between test (T) and reference (R) products required 90% confidence interval (CIs) for the geometric least square (LS) mean T/R ratio to be within 80–125% for the pharmacokinetic parameters, maximum plasma concentration (C(max)), and area under the curve (AUC(0–t)). RESULTS: The 90% CIs of geometric LS means of T/R ratio for C(max) and AUC(0–t) with vildagliptin tablets of 50 mg were 92.22–103.94% and 99.00–102.66%, respectively; corresponding results with FDC tablets for 50/850 mg tablets were 94.81–115.41% and 95.28–106.00% for vildagliptin and 90.87–101.18% and 90.56–100.09% for metformin; for 50/1000 mg tablets C(max) and AUC(0–t) were 105.56–122.30% and 98.30–107.55%, respectively, for vildagliptin and 92.14–103.73% and 94.60–101.81%, respectively, for metformin. Other parameters such as AUC(0–∞), time to maximum concentration (T(max)), and terminal half-life (t(1/2)) were comparable between test and reference products. Adverse events (AEs), mainly vomiting, were reported without relevant difference between test and reference products in each study. AEs were generally mild and transient. No severe or serious AEs occurred. CONCLUSIONS: The new generic drug products of vildagliptin and the FDCs of vildagliptin and metformin demonstrated bioequivalence to the approved originator products and are therefore expected to provide similar therapeutic effects. Springer Healthcare 2022-05-11 2022-06 /pmc/articles/PMC9174400/ /pubmed/35543870 http://dx.doi.org/10.1007/s13300-022-01269-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis 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, visithttp://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Klingberg, Ulrike Vadla, Hari Kiran Chary Prathap, Vamshi Ramana Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers |
title | Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers |
title_full | Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers |
title_fullStr | Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers |
title_full_unstemmed | Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers |
title_short | Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers |
title_sort | bioequivalence studies of new generic formulations of vildagliptin and fixed-drug combination of vildagliptin and metformin versus respective originator products in healthy volunteers |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174400/ https://www.ncbi.nlm.nih.gov/pubmed/35543870 http://dx.doi.org/10.1007/s13300-022-01269-1 |
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