A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo for Relief of Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD)

Inclusion Criteria:

1. The participant is ≥18 years of age at the time of informed consent signing.
2. In the opinion of the investigator or subinvestigators, the participant is capable ofunderstanding and complying with protocol requirements, including compliance with theelectronic diary.
3. The participant signs and dates a written informed consent form (ICF) and any requiredprivacy authorization prior to the initiation of any study procedures. The participantis informed of the full nature and purpose of the study, including possible risks andside effects. The participant has the ability to cooperate with the investigator.Ample time and opportunity should be given to read and understand verbal and/orwritten instructions.
4. The subject has a diagnosis of symptomatic gastroesophageal reflux disease (GERD) withheartburn as the subject's predominant symptom prior to the Screening Period, asdocumented in the subject's medical record.
5. History of onset of heartburn at least 6 months prior to the Screening Period.
6. Heartburn reported on 4 or more days during any consecutive 7-day period of theScreening Period as recorded in the electronic diary.
7. A female participant of childbearing potential who is or may be sexually active with anon-sterilized male partner agrees to routinely use adequate contraception from thesigning of informed consent until 4 weeks after the last dose of study drug.

Exclusion Criteria:

1. The participant has endoscopically confirmed erosive esophagitis (EE) during theScreening Period. Endoscopy conducted during the Screening Period should be performedafter participants meet Inclusion Criterion 6 (i.e., heartburn reported on 4 or moredays during any consecutive 7-day period of the Screening Period as recorded in theelectronic diary).
2. The participant has active irritable bowel syndrome (IBS) or has had a flare of IBSrequiring therapy within the prior 6 months.
3. The participant has a history of or is suspected of having functional uppergastrointestinal disorders, such as:
4. Functional heartburn, as described in the Rome IV Criteria.
5. Functional dyspepsia, as described in the Rome IV Criteria.
6. The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined esophagus)and/or definite dysplastic changes in the esophagus.
7. The participant has any other clinically significant condition affecting theesophagus, including eosinophilic esophagitis; esophageal varices; viral or fungalinfection; esophageal stricture; a history of radiation therapy, radiofrequencyablation, endoscopic mucosal resection, or cryotherapy to the esophagus; or anyhistory of caustic or physiochemical trauma (including sclerotherapy or esophagealvariceal band ligation). However, participants diagnosed with Schatzki's ring (mucosaltissue ring around lower esophageal sphincter) or hiatal hernia are eligible toparticipate.
8. The participant has scleroderma (systemic sclerosis) or systemic lupus erythematosus.
9. The participant has a history of surgery or endoscopic treatment affectinggastroesophageal reflux, including fundoplication and dilation for esophagealstricture (except dilation for a Schatzki's ring) or a history of gastric or duodenalsurgery (except endoscopic removal of benign polyps).
10. The participant has an active gastric or duodenal ulcer within 4 weeks before thefirst dose of study drug.
11. The participant requires or is expected to require use of prescription ornon-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) throughout the study.
12. The participant has received any investigational compound (including those inpost-marketing studies) within 30 days prior to the start of the Screening Period orvonoprazan in a clinical trial at any time (including participation in StudyNERD-201). A participant who has been screen failed from another clinical study andwho has not been dosed may be considered for enrollment in this study.
13. The participant is a study site employee, an immediate family member, or is in adependent relationship with a study site employee who is involved in the conduct ofthis study (eg, spouse, parent, child, sibling) or who may have consented underduress.
14. The participant has had clinically significant upper or lower gastrointestinalbleeding within 4 weeks prior to the Screening Period.
15. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretoryconditions.
16. The participant has a history of hypersensitivity or allergies to vonoprazan (including the formulation excipients: D-mannitol, microcrystalline cellulose,hydroxypropyl cellulose, fumaric acid, croscarmellose sodium, magnesium stearate,hypromellose, macrogol 8000, and titanium oxide, or red or yellow ferric oxide). Skintesting may be performed according to local standard practice to confirmhypersensitivity.
17. The participant has a history of alcohol abuse, illegal drug use, or drug addictionwithin the 12 months prior to screening, or regularly consumes >21 units of alcohol (1unit = 12 oz/300 mL beer, 1.5 oz/25 mL hard liquor/spirits, or 5 oz/100 mL wine) perweek based on self-report. Participants must have a negative urine drug screen forcannabinoids/tetrahydrocannabinol (including prescription cannabinoids) andnon-prescribed medications during the Screening Period.
18. The participant is taking any excluded medications or treatments listed in theprotocol, including prescription cannabinoids/tetrahydrocannabinol.
19. If female, the participant is pregnant, lactating, or intending to become pregnantbefore, during, or within 4 weeks after participating in this study, or intending todonate ova during such time period.
20. The participant has a history or clinical manifestations of significant centralnervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, othergastrointestinal, urological, endocrine, or hematological disease that, in the opinionof the investigator, would confound the study results or compromise participantsafety.
21. The participant requires hospitalization or has surgery scheduled during the course ofthe study (from Visit 1 to end of Follow-up Period at Visit 10) or has undergone majorsurgical procedures within 30 days prior to the Screening Period.
22. The participant has a history of malignancy (including mucosa-associated lymphoidtissue lymphoma) or has been treated for malignancy within 5 years prior to the startof the Screening Period (Visit 1). (The participant may be included in the study ifhe/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ).
23. The participant has acquired immunodeficiency syndrome or human immunodeficiency virusinfection, or tests positive for the hepatitis B surface antigen, hepatitis C virus (HCV) antibody, or HCV-ribonucleic acid (RNA). However, participants who test positivefor HCV antibody but negative for HCV-RNA are permitted to participate.
24. The participant has any of the following abnormal laboratory test values at the startof the Screening Period:
25. Creatinine levels: >2 mg/dL (>177 μmol/L).
26. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upperlimit of normal (ULN) or total bilirubin >2 × ULN (except for participants with adiagnosis of Gilbert's syndrome).
27. The subject tests positive for active H pylori infection during the Screening Period,after ≥4 weeks free from antibiotics and bismuth and ≥2 weeks free from PPIs andhistamine-2 receptor antagonists (H2RAs).