A Unblinded Study of TAK-438 (20 mg) for Prevention of Recurrence of Gastric or Duodenal Ulcer During Long-Term Low-Dose Aspirin Therapy

The purpose of this study is to study the safety and efficacy of TAK-438, once daily (QD), in participants with a history of gastric or duodenal ulcer requiring long-term low-dose aspirin therapy will be investigated.

Inclusion Criteria:

1. Participants who, in the opinion of the principal investigator or subinvestigator, are capable of understanding the details of the study and complying with them.

2. Prior to study commencement, participants who are capable of signing and dating the information/consent form.

3. Participants with a chronic disease (ischaemic cardiac disease, ischaemic cerebrovascular disease, etc.) which requires continuous low-dose aspirin oral therapy for prevention of thromboembolism during the treatment period.

4. Participants who meet either 1 or 2 below according to gastric or duodenal endoscopy:

   • Ulcer scar (defined, in this study, as regenerative mucosa, convergence of mucosal fold, gastric wall transformation, etc) has been confirmed during endoscopy on the study drug initiation day (Visit 2).
   • Ulcer (mucosal defects of 3 mm or larger with white moss) or ulcer scar has been endoscopically confirmed before the study drug initiation day (Visit 2).

5. Outpatient participants (inpatients for examinations are acceptable).

6. Women with child-bearing potential must agree to routinely take appropriate contraceptive measures throughout treatment period, from giving consent to the study until 4 weeks after the final dose.

Exclusion Criteria:

1. Participants who received treatment with another study drug (including approved drugs under post-marketing surveillance) within 84 days prior to commencement of screening

2. Participants who have previously received TAK-438 in a clinical study or as a treatment

3. Participants who are employees of institutions participating in this study and family members of such employees, participants in a dependent relationship with employees of institutions involved in conduct of the study (e.g., spouse, parent, child, sibling), and participants who are under duress in giving their consent

4. Participant who have donated 400 mL or more of blood within 90 days prior to the commencement of screening

5. Participants with a plan to change the type, dosage or administration of low-dose aspirin.

6. Participants with ulcer (mucosal defects of 3 mm or larger with white moss) or active hemorrhage confirmed during gastric or duodenal endoscopy on the study drug initiation day (Visit 2)

7. Participants with small intestinal hemorrhage, large intestinal hemorrhage, or gastrointestinal hemorrhage of unknown cause

8. Participants with a history of surgery or scheduled surgery influencing gastric acid secretion (resection of upper gastrointestinal tract or vagotomy etc)

9. Participants with a history or complication of Zollinger-Ellison syndrome, or other gastric acid hypersecretion disorders

10. Participants with a history or complication of aspirin asthma

11. Participants who have a history of hypersensitivity or allergy to TAK-438 (including its excipients) or aspirin or salicylic acid agents.

12. Participants with current use of illicit drug or a history of drug abuse. and/or alcohol dependence within one year prior to the commencement of screening

13. Participants who require treatment with prohibited concomitant drugs or therapies (see 7.3)

14. Female participants who are pregnant or lactating; those who plan to become pregnant or donate ova during treatment period, from giving consent until 4 weeks after final dose

15. Participants with serious central nervous system disorders, cardiovascular disease, pulmonary disease, hepatic disease, renal disease, metabolic disease, gastrointestinal disorders, urinary disorders, endocrine disease, or blood dyscrasia

16. Participants who plan to undergo surgery requiring hospitalization or requires surgery during the study period

17. Participants with a history of a malignancy (or treatment thereof) within 5 years prior to the commencement of screening; however, participants with completely cured of basal cell carcinoma of skin or carcinoma in situ of the cervix may be included in the study.

18. Participants with acquired immune deficiency syndrome (AIDS; including HIV carriers) or hepatitis (including viral hepatitis carriers [HBs antigen positive or HCV antibody positive]); however, Participants who are hepatitis C virus (HCV) antigen negative or HCV-RNA negative may be included in the study.

19. Participants who meet either of the following laboratory test values at the beginning of screening (Visit 1)

    • Serum creatinine value: higher than 2 mg/dL
    • Alanine transaminase (ALT) or aspartate aminotransferase (AST): higher than 2.5 × the upper limit of normal
    • Total bilirubin: higher than 2.0 × the upper limit of normal