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Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial
INTRODUCTION: Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were repo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415995/ https://www.ncbi.nlm.nih.gov/pubmed/25855342 http://dx.doi.org/10.1007/s12325-015-0200-x |
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author | Sasaki, Takashi Seino, Yutaka Fukatsu, Atsushi Ubukata, Michito Sakai, Soichi Samukawa, Yoshishige |
author_facet | Sasaki, Takashi Seino, Yutaka Fukatsu, Atsushi Ubukata, Michito Sakai, Soichi Samukawa, Yoshishige |
author_sort | Sasaki, Takashi |
collection | PubMed |
description | INTRODUCTION: Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical development studies. We aimed to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple doses of luseogliflozin administered once daily for 7 days in Japanese patients with T2DM. METHODS: We conducted a randomized, placebo-controlled, single-blind, parallel-group, clinical pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo, Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics (including changes in UGE and plasma glucose concentrations), and safety of luseogliflozin. RESULTS: The plasma concentrations of luseogliflozin and its active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was greater in all luseogliflozin groups versus placebo. Least-squares mean differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg, respectively. On Day 7, the areas under the concentration–time curves for post-meal plasma glucose and the mean plasma glucose for 0–16 h were significantly lower in all luseogliflozin groups versus placebo. Seven patients had mild adverse events (AEs); all were resolved. No AEs led to study discontinuation. CONCLUSION: Once-daily administration of luseogliflozin for 7 days increased 24-h UGE in a dose-dependent manner, reduced plasma glucose concentrations, and was well tolerated in Japanese patients with T2DM. The pharmacokinetic and pharmacodynamic profile of luseogliflozin observed in this study supports its once-daily dosing regimen. FUNDING: Taisho Pharmaceutical Co., Ltd. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-015-0200-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4415995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-44159952015-05-07 Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial Sasaki, Takashi Seino, Yutaka Fukatsu, Atsushi Ubukata, Michito Sakai, Soichi Samukawa, Yoshishige Adv Ther Original Research INTRODUCTION: Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical development studies. We aimed to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple doses of luseogliflozin administered once daily for 7 days in Japanese patients with T2DM. METHODS: We conducted a randomized, placebo-controlled, single-blind, parallel-group, clinical pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo, Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics (including changes in UGE and plasma glucose concentrations), and safety of luseogliflozin. RESULTS: The plasma concentrations of luseogliflozin and its active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was greater in all luseogliflozin groups versus placebo. Least-squares mean differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg, respectively. On Day 7, the areas under the concentration–time curves for post-meal plasma glucose and the mean plasma glucose for 0–16 h were significantly lower in all luseogliflozin groups versus placebo. Seven patients had mild adverse events (AEs); all were resolved. No AEs led to study discontinuation. CONCLUSION: Once-daily administration of luseogliflozin for 7 days increased 24-h UGE in a dose-dependent manner, reduced plasma glucose concentrations, and was well tolerated in Japanese patients with T2DM. The pharmacokinetic and pharmacodynamic profile of luseogliflozin observed in this study supports its once-daily dosing regimen. FUNDING: Taisho Pharmaceutical Co., Ltd. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-015-0200-x) contains supplementary material, which is available to authorized users. Springer Healthcare 2015-04-09 2015 /pmc/articles/PMC4415995/ /pubmed/25855342 http://dx.doi.org/10.1007/s12325-015-0200-x Text en © The Author(s) 2015 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Research Sasaki, Takashi Seino, Yutaka Fukatsu, Atsushi Ubukata, Michito Sakai, Soichi Samukawa, Yoshishige Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial |
title | Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial |
title_full | Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial |
title_fullStr | Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial |
title_full_unstemmed | Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial |
title_short | Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial |
title_sort | pharmacokinetics, pharmacodynamics, and safety of luseogliflozin in japanese patients with type 2 diabetes mellitus: a randomized, single-blind, placebo-controlled trial |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415995/ https://www.ncbi.nlm.nih.gov/pubmed/25855342 http://dx.doi.org/10.1007/s12325-015-0200-x |
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