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Clin Transl Gastroenterol. 2015 Jun 25;6:e94. doi: 10.1038/ctg.2015.18.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects.

Author information

1
Takeda Pharmaceutical Company Ltd, Osaka, Japan.
2
Takeda Development Centre Europe Ltd, London, UK.
3
Takeda Pharmaceutical Company Ltd, Fujisawa, Japan.
4
Department of Gastroenterology and Hepatology, Saiseikai Nakatsu Hospital, Osaka, Japan.
5
Medical Co. LTA Honjo Clinic (current Sumida Hospital), Tokyo, Japan.
6
1] Richmond Pharmacology Ltd, London, UK [2] St George's University of London, London, UK.

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.

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