Phase 3 Study of TAK-438 10 mg in the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD)
Condition: Non-erosive Gastroesophageal Reflux Disease
MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic
Intervention: Placebo; TAK-438 10 mg
Intervention description: TAK-438 placebo-matching tablets; TAK-438 tablets
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 484.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study was to evaluate the efficacy and safety of oral TAK-438 10 mg
      once-daily in the treatment of non-erosive gastroesophageal reflux disease (NERD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. The participant signs and dates a written informed consent form prior to the
             initiation 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 with
             Grade M, the target number of participants in each grade is at least 30% of the total
             number of participants. Enrollment of patients with either Grade N or M will end when
             the number of enrolled participants with each grade exceeds 332, or 70% of the total
             planned number of participants.

          5. The participant experiences recurrent heartburn, on at least 2 days a week over the
             last 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 years
             at the time of informed consent signing. However, participants who are hospitalized
             only for examination purposes are also allowed to participate.

          7. A female participant of childbearing potential agrees to use routinely adequate
             contraception 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 the
             run-in period.

          9. The participant has experienced heartburn on at least 2 days in the last 1 week prior
             to randomization.

         10. The participant has appropriately provided in the patient's diary all the required
             information during the run-in period.

        Exclusion Criteria:

          1. The participant has received any investigational compound within 84 days prior to the
             first dose of study drug.

          2. The participant has received TAK-438 in a previous clinical study or as a therapeutic
             agent, 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 a
             dependent relationship with a study site employee who is involved in conduct of this
             study (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 the
             start of the run-in period (Visit 1).

          5. Endoscopic examination for entering this study fails to diagnose NERD within 84 days
             before the start of the run-in period (Visit 1).

          6. The participant has any complications affecting the esophagus, including Barrett's
             esophagus (3 cm or more, long segment Barrett's esophagus [LSBE]), eosinophilic
             esophagitis, esophageal varices, scleroderma, viral or fungal infection, and
             esophageal 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 esophageal
             sphincter) are permitted to participate.

          7. The participant has a history of surgery or treatment affecting gastroesophageal
             reflux, including fundoplication and mechanical dilatation for esophageal stenosis
             (except Schatzki's ring), or a history of gastric or duodenal surgery (except
             endoscopic removal of benign polyps).

          8. The participant has acute upper gastrointestinal bleeding or gastric or duodenal
             ulcer, characterized by a defective mucosa with white coating, within 30 days prior to
             the start of the run-in period (Visit 1). However, participants with gastric or
             duodenal 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 acid
             hypersecretion disorders.

         11. The participant has, or has a history of chest pain due to cardiac disease, or has
             chest pain suspectedly caused by cardiac disease within 1 year prior to the start of
             the run-in period (Visit 1).

         12. The participant has any other concurrent upper gastrointestinal symptoms more severe
             than heartburn.

         13. The participant has depression.

         14. The participant has, has a history of, or is suspected of functional upper
             gastrointestinal disorders, such as functional dyspepsia and functional heartburn
             diagnosed by the Rome IV criteria.

         15. The participant has a history of hypersensitivity or allergies to TAK-438 (including
             the formulation excipients).

         16. The participant has a history or complication of drug abuse (defined as any illicit
             drug 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 become
             pregnant or to donate ova any time between the informed consent signing and 4 weeks
             after the last dose of study drug.

         19. The participant has any serious neurological, cardiovascular, pulmonary, hepatic,
             renal, metabolic, gastrointestinal, urologic, endocrinological, or hematologic
             diseases.

         20. The participant needs surgery requiring hospitalization during the course of the
             study, or surgery requiring hospitalization is scheduled for the participant during
             the course of the study.

         21. The participant has a history of malignancy or is treated for malignancy within 5
             years prior to the start of the run-in period (Visit 1). However, participants who
             have recovered completely from cutaneous basal cell carcinoma or from cervical
             carcinoma in situ are permitted to participate.

         22. The participant has acquired immunodeficiency syndrome (AIDS) or hepatitis, is a human
             immunodeficiency virus (HIV) carrier, or tested positive for the hepatitis B virus
             surface antigen (HBsAg) or the hepatitis C virus (HCV) antibody. However, participants
             who 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 at
             the start of the run-in period (Visit 1):

               -  Creatinine > 2 mg/dL.

               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit
                  of normal (ULN).

               -  Bilirubin (Total bilirubin) > ULN.