Sakurai, Y;
Nishimura, A;
Kennedy, G;
Hibberd, M;
Jenkins, R;
Okamoto, H;
Yoneyama, T;
Jenkins, H;
Ashida, K;
Irie, S;
et al.
Sakurai, Y; Nishimura, A; Kennedy, G; Hibberd, M; Jenkins, R; Okamoto, H; Yoneyama, T; Jenkins, H; Ashida, K; Irie, S; Täubel, J
(2015)
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects.
Clin Transl Gastroenterol, 6 (6).
e94.
ISSN 2155-384X
https://doi.org/10.1038/ctg.2015.18
SGUL Authors: Taubel, Jorg
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Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (672kB) | Preview |
Abstract
OBJECTIVES: To evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-438 (vonoprazan, a potassium-competitive acid blocker) in healthy male subjects. METHODS: In two phase I, randomized, double-blind, placebo-controlled, single rising-dose studies, healthy male subjects (Japan N=84; UK N=63) received a single TAK-438 dose (1-120 mg in Japan and 1-40 mg in the UK). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH). RESULTS: Plasma concentration-time profiles of TAK-438 at all dose levels showed rapid absorption (median Tmax up to 2 h). Estimated mean elimination half-life was up to 9 h. Exposure was slightly greater than dose proportional. No clear difference in TAK-438 pharmacokinetics was observed between Japanese and non-Japanese subjects. Acid suppression was dose dependent and similar in both studies. The 24-h intragastric pH ≥4 holding time ratio with 40 mg TAK-438 was 92% in Japan and 87% in the UK. TAK-438 was well tolerated, with no adverse events reported in Japanese subjects; 10 of 63 UK subjects experienced 12 treatment-emergent adverse events (non-serious). Increases in serum gastrin and pepsinogen I and II concentrations were observed at doses ≥10 mg, but there were no changes in alanine aminotransferase concentrations. CONCLUSIONS: Single oral doses of TAK-438 20-120 mg caused rapid, profound, and 24-h suppression of gastric acid secretion in healthy male subjects, regardless of geographical region, and TAK-438 was well tolerated at all doses studied, making it a potential alternative to proton pump inhibitors for the treatment of acid-related disorders.
Item Type: | Article |
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Additional Information: | Copyright © 2015 American College of Gastroenterology Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: | Clin Transl Gastroenterol |
ISSN: | 2155-384X |
Language: | eng |
Publisher License: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 |
PubMed ID: | 26111126 |
Web of Science ID: | WOS:000359476400007 |
Go to PubMed abstract | |
URI: | https://openaccess.sgul.ac.uk/id/eprint/114005 |
Publisher's version: | https://doi.org/10.1038/ctg.2015.18 |
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