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

Sakurai Y, Nishimura A, Kennedy G, Hibberd M, Jenkins R, Okamoto H, Yoneyama T, Jenkins H, Ashida K, Irie S, Täubel J - Clin Transl Gastroenterol (2015)

Bottom Line: Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH).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).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.

View Article: PubMed Central - PubMed

Affiliation: Takeda Pharmaceutical Company Ltd, Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Mean intragastric pH–time profiles after a single dose of TAK-438 (1–120 mg in Japan and 1–40 mg in the UK) in the Japanese (left) and UK (right) single rising-dose studies in healthy male subjects (red vertical lines indicate when meals were given) (Pharmacodynamic analysis set; Japan N=82, UK N=63).
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fig4: Mean intragastric pH–time profiles after a single dose of TAK-438 (1–120 mg in Japan and 1–40 mg in the UK) in the Japanese (left) and UK (right) single rising-dose studies in healthy male subjects (red vertical lines indicate when meals were given) (Pharmacodynamic analysis set; Japan N=82, UK N=63).

Mentions: The mean intragastric pH–time parameters after a single dose of TAK-438 showed rapid onset, dose-dependent acid suppression in both studies, with an upward shift in pH compared with placebo (Figure 4).


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

Sakurai Y, Nishimura A, Kennedy G, Hibberd M, Jenkins R, Okamoto H, Yoneyama T, Jenkins H, Ashida K, Irie S, Täubel J - Clin Transl Gastroenterol (2015)

Mean intragastric pH–time profiles after a single dose of TAK-438 (1–120 mg in Japan and 1–40 mg in the UK) in the Japanese (left) and UK (right) single rising-dose studies in healthy male subjects (red vertical lines indicate when meals were given) (Pharmacodynamic analysis set; Japan N=82, UK N=63).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816246&req=5

fig4: Mean intragastric pH–time profiles after a single dose of TAK-438 (1–120 mg in Japan and 1–40 mg in the UK) in the Japanese (left) and UK (right) single rising-dose studies in healthy male subjects (red vertical lines indicate when meals were given) (Pharmacodynamic analysis set; Japan N=82, UK N=63).
Mentions: The mean intragastric pH–time parameters after a single dose of TAK-438 showed rapid onset, dose-dependent acid suppression in both studies, with an upward shift in pH compared with placebo (Figure 4).

Bottom Line: Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH).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).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.

View Article: PubMed Central - PubMed

Affiliation: Takeda Pharmaceutical Company Ltd, Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus