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)
Condition: Non-Erosive Gastro-Esophageal Reflux Disease; Heartburn
MeSH terms: Gastroesophageal Reflux; Heartburn
Intervention: Vonoprazan; Placebo
Intervention description: Orally via capsule; Orally via capsule
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 776.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NERD; Vonoprazan

Summary:

      The primary objectives of this study are to assess the efficacy of vonoprazan (10 mg and 20
      mg once daily [QD]) compared to placebo (QD) in relief of heartburn over 4 weeks in
      participants with NERD.
    

Eligibility criteria:

        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 of
             understanding and complying with protocol requirements, including compliance with the
             electronic diary.

          3. The participant signs and dates a written informed consent form (ICF) and any required
             privacy authorization prior to the initiation of any study procedures. The participant
             is informed of the full nature and purpose of the study, including possible risks and
             side effects. The participant has the ability to cooperate with the investigator.
             Ample time and opportunity should be given to read and understand verbal and/or
             written instructions.

          4. The subject has a diagnosis of symptomatic gastroesophageal reflux disease (GERD) with
             heartburn as the subject's predominant symptom prior to the Screening Period, as
             documented 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 the
             Screening Period as recorded in the electronic diary.

          7. A female participant of childbearing potential who is or may be sexually active with a
             non-sterilized male partner agrees to routinely use adequate contraception from the
             signing 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 the
             Screening Period. Endoscopy conducted during the Screening Period should be performed
             after participants meet Inclusion Criterion 6 (i.e., heartburn reported on 4 or more
             days during any consecutive 7-day period of the Screening Period as recorded in the
             electronic diary).

          2. The participant has active irritable bowel syndrome (IBS) or has had a flare of IBS
             requiring therapy within the prior 6 months.

          3. The participant has a history of or is suspected of having functional upper
             gastrointestinal disorders, such as:

               1. Functional heartburn, as described in the Rome IV Criteria.

               2. Functional dyspepsia, as described in the Rome IV Criteria.

          4. The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined esophagus)
             and/or definite dysplastic changes in the esophagus.

          5. The participant has any other clinically significant condition affecting the
             esophagus, including eosinophilic esophagitis; esophageal varices; viral or fungal
             infection; esophageal stricture; a history of radiation therapy, radiofrequency
             ablation, endoscopic mucosal resection, or cryotherapy to the esophagus; or any
             history of caustic or physiochemical trauma (including sclerotherapy or esophageal
             variceal band ligation). However, participants diagnosed with Schatzki's ring (mucosal
             tissue ring around lower esophageal sphincter) or hiatal hernia are eligible to
             participate.

          6. The participant has scleroderma (systemic sclerosis) or systemic lupus erythematosus.

          7. The participant has a history of surgery or endoscopic treatment affecting
             gastroesophageal reflux, including fundoplication and dilation for esophageal
             stricture (except dilation for a Schatzki's ring) or a history of gastric or duodenal
             surgery (except endoscopic removal of benign polyps).

          8. The participant has an active gastric or duodenal ulcer within 4 weeks before the
             first dose of study drug.

          9. The participant requires or is expected to require use of prescription or
             non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists
             (H2RAs) throughout the study.

         10. The participant has received any investigational compound (including those in
             post-marketing studies) within 30 days prior to the start of the Screening Period or
             vonoprazan in a clinical trial at any time (including participation in Study
             NERD-201). A participant who has been screen failed from another clinical study and
             who has not been dosed may be considered for enrollment in this study.

         11. The participant is a study site employee, an immediate family member, or is in a
             dependent relationship with a study site employee who is involved in the conduct of
             this study (eg, spouse, parent, child, sibling) or who may have consented under
             duress.

         12. The participant has had clinically significant upper or lower gastrointestinal
             bleeding within 4 weeks prior to the Screening Period.

         13. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory
             conditions.

         14. 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). Skin
             testing may be performed according to local standard practice to confirm
             hypersensitivity.

         15. The participant has a history of alcohol abuse, illegal drug use, or drug addiction
             within the 12 months prior to screening, or regularly consumes >21 units of alcohol (1
             unit = 12 oz/300 mL beer, 1.5 oz/25 mL hard liquor/spirits, or 5 oz/100 mL wine) per
             week based on self-report. Participants must have a negative urine drug screen for
             cannabinoids/tetrahydrocannabinol (including prescription cannabinoids) and
             non-prescribed medications during the Screening Period.

         16. The participant is taking any excluded medications or treatments listed in the
             protocol, including prescription cannabinoids/tetrahydrocannabinol.

         17. If female, the participant is pregnant, lactating, or intending to become pregnant
             before, during, or within 4 weeks after participating in this study, or intending to
             donate ova during such time period.

         18. The participant has a history or clinical manifestations of significant central
             nervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, other
             gastrointestinal, urological, endocrine, or hematological disease that, in the opinion
             of the investigator, would confound the study results or compromise participant
             safety.

         19. The participant requires hospitalization or has surgery scheduled during the course of
             the study (from Visit 1 to end of Follow-up Period at Visit 10) or has undergone major
             surgical procedures within 30 days prior to the Screening Period.

         20. The participant has a history of malignancy (including mucosa-associated lymphoid
             tissue lymphoma) or has been treated for malignancy within 5 years prior to the start
             of the Screening Period (Visit 1). (The participant may be included in the study if
             he/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ).

         21. The participant has acquired immunodeficiency syndrome or human immunodeficiency virus
             infection, or tests positive for the hepatitis B surface antigen, hepatitis C virus
             (HCV) antibody, or HCV-ribonucleic acid (RNA). However, participants who test positive
             for HCV antibody but negative for HCV-RNA are permitted to participate.

         22. The participant has any of the following abnormal laboratory test values at the start
             of the Screening Period:

               1. Creatinine levels: >2 mg/dL (>177 μmol/L).

               2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper
                  limit of normal (ULN) or total bilirubin >2 × ULN (except for participants with a
                  diagnosis of Gilbert's syndrome).

         23. 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 and
             histamine-2 receptor antagonists (H2RAs).