Phase 3 Study of TAK-438 10 mg in the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD)

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding andcomplying with protocol requirements.

2. The participant signs and dates a written informed consent form prior to theinitiation of any study procedures.

3. The participant with NERD.

4. The participant is endoscopically confirmed to have the modified Los Angeles (LA)Classification Grade N or M at the start of the run-in period (Visit 1). To allow efficacy evaluation in the participants with Grade N as well as in those withGrade M, the target number of participants in each grade is at least 30% of the totalnumber of participants. Enrollment of patients with either Grade N or M will end whenthe number of enrolled participants with each grade exceeds 332, or 70% of the totalplanned number of participants.

5. The participant experiences recurrent heartburn, on at least 2 days a week over thelast 3 weeks prior to the start of the run-in period (Visit 1).

6. The participant is either a male or female outpatient with a minimum age of 20 yearsat the time of informed consent signing. However, participants who are hospitalizedonly for examination purposes are also allowed to participate.

7. A female participant of childbearing potential agrees to use routinely adequatecontraception from signing of informed consent throughout the duration of the study,and for 4 weeks after the last dose of study drug.

8. The participant's compliance to the study drug has been good (75% or better) in therun-in period.

9. The participant has experienced heartburn on at least 2 days in the last 1 week priorto randomization.

10. The participant has appropriately provided in the patient's diary all the requiredinformation during the run-in period.

Exclusion Criteria:

1. The participant has received any investigational compound within 84 days prior to thefirst dose of study drug.

2. The participant has received TAK-438 in a previous clinical study or as a therapeuticagent, except one with experience of receiving TAK-438 as an adjunct therapy for H.pylori eradication, who can be enrolled in this study.

3. The participant is an immediate family member, study site employee, or is in adependent relationship with a study site employee who is involved in conduct of thisstudy (eg, spouse, parent, child, sibling) or may consent under duress.

4. The participant has donated at least 400 mL of blood within the 90 days prior to thestart of the run-in period (Visit 1).

5. Endoscopic examination for entering this study fails to diagnose NERD within 84 daysbefore the start of the run-in period (Visit 1).

6. The participant has any complications affecting the esophagus, including Barrett'sesophagus (3 cm or more, long segment Barrett's esophagus [LSBE]), eosinophilicesophagitis, esophageal varices, scleroderma, viral or fungal infection, andesophageal stenosis; a history of radiation therapy or cryotherapy for the esophagus;or caustic or physiochemical trauma (eg, esophageal sclerotherapy). However,participants with Barrett's mucosa (less than 3 cm, short segment Barrett's esophagus [SSBE]) or Schatzki's ring (a mucosal tissue ring lining the inferior esophagealsphincter) are permitted to participate.

7. The participant has a history of surgery or treatment affecting gastroesophagealreflux, including fundoplication and mechanical dilatation for esophageal stenosis (except Schatzki's ring), or a history of gastric or duodenal surgery (exceptendoscopic removal of benign polyps).

8. The participant has acute upper gastrointestinal bleeding or gastric or duodenalulcer, characterized by a defective mucosa with white coating, within 30 days prior tothe start of the run-in period (Visit 1). However, participants with gastric orduodenal erosion are permitted to participate.

9. The participant has acute gastritis or acute exacerbation of chronic gastritis.

10. The participant has, or has a history of, Zollinger-Ellison syndrome or gastric acidhypersecretion disorders.

11. The participant has, or has a history of chest pain due to cardiac disease, or haschest pain suspectedly caused by cardiac disease within 1 year prior to the start ofthe run-in period (Visit 1).

12. The participant has any other concurrent upper gastrointestinal symptoms more severethan heartburn.

13. The participant has depression.

14. The participant has, has a history of, or is suspected of functional uppergastrointestinal disorders, such as functional dyspepsia and functional heartburndiagnosed by the Rome IV criteria.

15. The participant has a history of hypersensitivity or allergies to TAK-438 (includingthe formulation excipients).

16. The participant has a history or complication of drug abuse (defined as any illicitdrug use) or of alcohol abuse within 1 years prior to the start of the run-in period (Visit 1).

17. The participant requires any excluded medications or treatments.

18. The female participant who is pregnant, is lactating, or is intending to becomepregnant or to donate ova any time between the informed consent signing and 4 weeksafter the last dose of study drug.

19. The participant has any serious neurological, cardiovascular, pulmonary, hepatic,renal, metabolic, gastrointestinal, urologic, endocrinological, or hematologicdiseases.

20. The participant needs surgery requiring hospitalization during the course of thestudy, or surgery requiring hospitalization is scheduled for the participant duringthe course of the study.

21. The participant has a history of malignancy or is treated for malignancy within 5years prior to the start of the run-in period (Visit 1). However, participants whohave recovered completely from cutaneous basal cell carcinoma or from cervicalcarcinoma in situ are permitted to participate.

22. The participant has acquired immunodeficiency syndrome (AIDS) or hepatitis, is a humanimmunodeficiency virus (HIV) carrier, or tested positive for the hepatitis B virussurface antigen (HBsAg) or the hepatitis C virus (HCV) antibody. However, participantswho tested negative for HCV antigen or HCV-RNA are permitted to participate.

23. The participant has any of the following abnormal clinical laboratory test values atthe start of the run-in period (Visit 1):

• Creatinine > 2 mg/dL.

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limitof normal (ULN).

• Bilirubin (Total bilirubin) > ULN.