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Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products
INTRODUCTION: Three studies compared the bioequivalence (BE) of new generic tablet formulations of sitagliptin (100 mg; fasting) and the fixed-dose combination (FDC) of sitagliptin/metformin (50/850 mg, 50/1000 mg; both fed) in healthy volunteers with the same tablet strengths of the reference produ...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9943811/ https://www.ncbi.nlm.nih.gov/pubmed/36526947 http://dx.doi.org/10.1007/s13300-022-01349-2 |
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author | Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Uhl, Wolfgang Ribot, Olga Varanasi, Kanthikiran V. S. Rodríguez, Laura Torrejón, Javier Gómez, Luis |
author_facet | Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Uhl, Wolfgang Ribot, Olga Varanasi, Kanthikiran V. S. Rodríguez, Laura Torrejón, Javier Gómez, Luis |
author_sort | Schnaars, Yvonne |
collection | PubMed |
description | INTRODUCTION: Three studies compared the bioequivalence (BE) of new generic tablet formulations of sitagliptin (100 mg; fasting) and the fixed-dose combination (FDC) of sitagliptin/metformin (50/850 mg, 50/1000 mg; both fed) in healthy volunteers with the same tablet strengths of the reference products Januvia and Janumet. METHODS: The study design was open-label, single-dose, randomized with two-way crossover periods. Blood sampling was performed for 72/48 h in the sitagliptin/FDC studies, respectively. Primary pharmacokinetic (PK) parameters for sitagliptin and metformin were area under the plasma concentration–time curve from time 0 to last timepoint of measurable concentration (AUC(0–t)) and maximum plasma concentration (C(max)). Test (T) and reference (R) formulations proved bioequivalent if 90% confidence interval (CI) of geometric least-squares mean ratio for AUC(0–t) and C(max) were within BE acceptance range of 80.00–125.00%. Safety evaluations included vital signs, clinical laboratory tests, and adverse events (AEs). RESULTS: Treated/evaluable volunteers for BE per study were: 30/28 (sitagliptin 100 mg), 26/25 (FDC 50/850 mg), and 26/24 (FDC 50/1000 mg). The 90% CI of the geometric means of T/R ratios for primary PK parameters were within predefined BE limits: CI for AUC(0–t) and C(max) were 95.83–100.37% and 91.85–109.56% (sitagliptin 100 mg); 100.84–103.69% and 93.44–105.10% (FDC 50/850 mg), and 101.26–105.20% and 98.71–112.89% (FDC 50/1000 mg); respective values for metformin were 94.23–101.89% and 91.66–99.38% (FDC 50/850 mg) and 98.45–104.89% and 96.79–105.62% (FDC 50/1000 mg). All AEs were nonserious, transient, and mostly mild. Safety evaluations did not reveal any relevant difference between T and R formulations. CONCLUSIONS: The new generic tablet formulations of sitagliptin 100 mg and the FDCs sitagliptin/metformin 50/850 mg and 50/1000 mg demonstrated bioequivalence to originator reference products. Therefore, the new products are expected to provide efficacy and tolerability similar to those of the reference products in the treatment of patients with type 2 diabetes (T2D). TRIAL REGISTRATION: EudraCT EU Clinical Trials Registry (2014-005437-31); ClinicalTrials.gov Registry (NCT05549570 and NCT05549583, both retrospectively registered on 20 September 2022). |
format | Online Article Text |
id | pubmed-9943811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-99438112023-02-23 Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products Schnaars, Yvonne Gaikwad, Sumedh Gottwald-Hostalek, Ulrike Uhl, Wolfgang Ribot, Olga Varanasi, Kanthikiran V. S. Rodríguez, Laura Torrejón, Javier Gómez, Luis Diabetes Ther Original Research INTRODUCTION: Three studies compared the bioequivalence (BE) of new generic tablet formulations of sitagliptin (100 mg; fasting) and the fixed-dose combination (FDC) of sitagliptin/metformin (50/850 mg, 50/1000 mg; both fed) in healthy volunteers with the same tablet strengths of the reference products Januvia and Janumet. METHODS: The study design was open-label, single-dose, randomized with two-way crossover periods. Blood sampling was performed for 72/48 h in the sitagliptin/FDC studies, respectively. Primary pharmacokinetic (PK) parameters for sitagliptin and metformin were area under the plasma concentration–time curve from time 0 to last timepoint of measurable concentration (AUC(0–t)) and maximum plasma concentration (C(max)). Test (T) and reference (R) formulations proved bioequivalent if 90% confidence interval (CI) of geometric least-squares mean ratio for AUC(0–t) and C(max) were within BE acceptance range of 80.00–125.00%. Safety evaluations included vital signs, clinical laboratory tests, and adverse events (AEs). RESULTS: Treated/evaluable volunteers for BE per study were: 30/28 (sitagliptin 100 mg), 26/25 (FDC 50/850 mg), and 26/24 (FDC 50/1000 mg). The 90% CI of the geometric means of T/R ratios for primary PK parameters were within predefined BE limits: CI for AUC(0–t) and C(max) were 95.83–100.37% and 91.85–109.56% (sitagliptin 100 mg); 100.84–103.69% and 93.44–105.10% (FDC 50/850 mg), and 101.26–105.20% and 98.71–112.89% (FDC 50/1000 mg); respective values for metformin were 94.23–101.89% and 91.66–99.38% (FDC 50/850 mg) and 98.45–104.89% and 96.79–105.62% (FDC 50/1000 mg). All AEs were nonserious, transient, and mostly mild. Safety evaluations did not reveal any relevant difference between T and R formulations. CONCLUSIONS: The new generic tablet formulations of sitagliptin 100 mg and the FDCs sitagliptin/metformin 50/850 mg and 50/1000 mg demonstrated bioequivalence to originator reference products. Therefore, the new products are expected to provide efficacy and tolerability similar to those of the reference products in the treatment of patients with type 2 diabetes (T2D). TRIAL REGISTRATION: EudraCT EU Clinical Trials Registry (2014-005437-31); ClinicalTrials.gov Registry (NCT05549570 and NCT05549583, both retrospectively registered on 20 September 2022). Springer Healthcare 2022-12-16 2023-02 /pmc/articles/PMC9943811/ /pubmed/36526947 http://dx.doi.org/10.1007/s13300-022-01349-2 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, visit http://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 Uhl, Wolfgang Ribot, Olga Varanasi, Kanthikiran V. S. Rodríguez, Laura Torrejón, Javier Gómez, Luis Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products |
title | Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products |
title_full | Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products |
title_fullStr | Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products |
title_full_unstemmed | Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products |
title_short | Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin–Metformin Fixed-Dose Combination Compared with the Originator Products |
title_sort | bioequivalence evaluation in healthy volunteers: new generic formulations of sitagliptin and sitagliptin–metformin fixed-dose combination compared with the originator products |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9943811/ https://www.ncbi.nlm.nih.gov/pubmed/36526947 http://dx.doi.org/10.1007/s13300-022-01349-2 |
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