The purpose of this study is to investigate the acid-inhibitory effect of multiple oral doses of Vonoprazan (TAK-438) and the relative effect of vonoprazan versus two controls (esomeprazole and rabeprazole sodium) in healthy Japanese adult male participants with the CYP2C19 extensive metabolizer (EM) genotype.

This is a Phase 3 open-label crossover study to evaluate the acid-inhibitory effect following 7 days multiple doses of vonoprazan (20 mg per dose) and esomeprazole (20 mg per dose) (Cohort 1) or vonoprazan (20 mg per dose) and rabeprazole sodium (10 mg per dose) (Cohort 2) in healthy Japanese adult male participants (CYP2C19 genotype: EM). There will be a total of 20 participants, 5 per group for both Cohorts 1 and 2. At least 2 participants each with the homo EM (*1/*1) or hetero EM (*1/*2, *1/*3) CYP2C19 genotype will be enrolled among the 5 participants per group.

The drug being tested in this study is called vonoprazan. This study will look at the acid inhibitory effect following 7 days multiple doses of vonoprazan and esomeprazole (Cohort 1) or vonoprazan and rabeprazole sodium (Cohort 2) in healthy Japanese adult male participants with the CYP2C19 EM genotype.

The study will enroll a total of 20 participants, 5 per group for both Cohorts. At least 2 participants each with the homo EM (*1/*1) or hetero EM (*1/*2, *1/*3) CYP2C19 genotype will be enrolled among the 5 participants per group.

• Group A, Cohort 1: vonoprazan (20 mg per dose for 7 days) followed by esomeprazole (20 mg per dose for 7 days)
• Group B, Cohort 1: esomeprazole (20 mg per dose for 7 days) followed by TAK-438 (20 mg per dose for 7 days)
• Group C, Cohort 2: vonoprazan (20 mg per dose for 7 days) followed by rabeprazole sodium (10 mg per dose for 7 days)
• Group D, Cohort 2: rabeprazole sodium (10 mg per dose for 7 days) followed by vonoprazan (20 mg per dose for 7 days).

All participants will be asked to take Study Medication at the same time each day throughout the study. This single center trial will be conducted in Japan. The overall time to participate in this study is 31 days.

Inclusion Criteria:

1. Is a healthy Japanese adult male volunteer.
2. Is aged 20 to 45 years, inclusive, at the time of informed consent.
3. Has been confirmed at CYP2C19 genotyping as an Extensive Metabolizer [EM (*1/*1,*1/*2,*1/*3)].
4. Capable of understanding and complying with the protocol requirements.
5. The participant signs and dates a written informed consent form prior to the initiation of any study procedures.
6. Weighs 50 kg or more and has body mass index (BMI) of 18.5 or more and less than 25.0 kg/m^2 at Screening or admission (Day -3).
7. H. pylori-negative at Screening.

Exclusion Criteria:

1. Has undergone resection of the upper gastrointestinal tract or vagotomy.
2. Was determined to have hypoacidity or anacidity.
3. Has a present or past history of acid-related disease (reflux esophagitis, gastric ulcer, duodenal ulcer, non-erosive gastroesophageal reflux, Barrett's esophagus, Zollinger-Ellison syndrome, etc.).
4. Has undergone eradication of H. pylori within 6 months prior to the start of the study drug administration.
5. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormalities which may impact the ability of the subject to participate or potentially confound the study results.
6. Has a known hypersensitivities or allergies to drugs or food.
7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the start of the study drug administration.
8. Has poor peripheral venous access.
9. Had 200 mL or more of whole blood drawn within 4 weeks (28 days) prior to the start of the study drug administration or 400 mL or more of whole blood drawn within 12 weeks (84 days) prior to the start of the study drug administration.
10. Had a total volume of 800 mL or more of whole blood drawn within 52 weeks (364 days) prior to the start of the study drug administration.
11. Has undergone blood component draw within 2 weeks (14 days) prior to the start of the study drug administration.
12. Requires treatment with any of the excluded medications specified in the study or requires nutrition with any vitamin supplements or foods prohibited in the study.
13. Has received study medication within 16 weeks (112 days) prior to the start of the study drug administration.
14. Has received vonoprazan (TAK-438) in the past.
15. Has a history of cancer.
16. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen or serological reaction for syphilis at Screening.
17. Has a Screening or admission (Day -3) abnormal clinically significant electrocardiogram (ECG).
18. Has abnormal Screening or admission (Day -3) laboratory values that suggest a clinically significant underlying disease or subject with the following lab abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice the upper limit of the normal range.
19. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
20. Participant who, in the opinion of the investigator or sub-investigator, is unlikely to comply with the protocol or is unsuitable for any other reasons.

31 Days

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.