A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease
Condition: Non-Erosive Gastro-Esophageal Reflux Disease; Heartburn
MeSH terms: Gastroesophageal Reflux; Heartburn
Intervention: Vonoprazan; Placebo
Intervention description: Orally via capsules; Orally via capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: During the Run-In Period, participants will receive open-label vonoprazan.
Enrollment: 458.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Symptomatic Non-Erosive Gastroesophageal Reflux Disease; NERD; Vonoprazan; Heartburn

Summary:

      The primary objectives of this study are to assess the efficacy of vonoprazan (10 mg, 20 mg,
      and 40 mg On-Demand) compared to placebo (On-Demand) in relief of episodic heartburn over 6
      weeks in participants with symptomatic non-erosive gastroesophageal reflux disease (NERD),
      and to assess the safety of vonoprazan (10 mg, 20 mg, and 40 mg On-Demand) compared to
      placebo (On-Demand) in participants with symptomatic NERD.
    

Eligibility criteria:

        Inclusion Criteria for Run-In Period

          1. The participant is ≥18 years of age at the time of informed consent signing.

          2. In the opinion of the investigator or sub investigators, the participant is capable of
             understanding and complying with protocol requirements.

          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 participant identified their main symptom as heartburn, a burning sensation in the
             retrosternal area (behind the breastbone).

          5. History of episodes of heartburn for 6 months or longer prior to screening.

          6. Heartburn reported on 4 or more days during any 7 consecutive days in 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.

        Inclusion Criteria for On-Demand Treatment Period

          1. The participant completes the Run-In Period, during which the participant was at least
             80% compliant with open-label study drug.

          2. The participant has stable disease, ie, no heartburn the last 7 days of the Run-In
             Period.

          3. The participant continues to fulfill all eligibility criteria for the Run-In Period
             (except Inclusion Criteria 4).

          4. Participant completes at least 80% of diary entries during Run-In Period, including
             80% of diary entries over the last 7 days.

        Exclusion Criteria for Run-In Period

          1. Endoscopically confirmed erosive esophagitis (EE) during the Screening Period assessed
             by the investigator. Endoscopy should be performed after participants meet Inclusion
             Criteria 6. Any endoscopic confirmation performed in a routine clinical setting within
             7 days before signing the informed consent is acceptable to use for the purpose of
             fulfilling the screening requirement.

          2. The participant has active irritable bowel syndrome (IBS) or 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 heartburn
             diagnosed by the Rome IV criteria.

          4. The participant has a history of or is suspected of having functional dyspepsia
             diagnosed by the Rome IV criteria.

          5. The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined esophagus)
             and/or definite dysplastic changes in the esophagus.

          6. 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.

          7. The participant has scleroderma (systemic sclerosis).

          8. The participant has a history of surgery or endoscopic treatment affecting
             gastroesophageal reflux, including fundoplication and dilation for esophageal
             stricture (except Schatzki's ring) or a history of gastric or duodenal surgery (except
             endoscopic removal of benign polyps).

          9. The participant has an active gastric or duodenal ulcer within 4 weeks before the
             first dose of study drug.

         10. Use of prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2
             receptor antagonists (H2RAs) throughout the study.

         11. The participant has received vonoprazan in a clinical trial at any time or any other
             investigational compound (including those in post-marketing studies) within 30 days
             prior to the start of the Screening Period. 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.

         12. 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.

         13. The participant has cutaneous lupus erythematosus or systemic lupus erythematosus.

         14. The participant has had clinically significant upper or lower gastrointestinal
             bleeding within 4 weeks prior to screening.

         15. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory
             conditions.

         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, titanium oxide, or red or yellow ferric oxide). Skin
             testing may be performed according to local standard practice to confirm
             hypersensitivity.

         17. The participant has a history of alcohol abuse, illegal drug use, drug addiction, 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 within the 12
             months prior to screening. Participants must have a negative urine drug screen for
             cannabinoids/ tetrahydrocannabinol and nonprescribed medications at screening.
             Participants taking prescription drugs (except prescription
             cannabinoids/tetrahydrocannabinol) will be allowed.

         18. The participant is taking any excluded medications or treatments listed in the
             protocol.

         19. 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.

         20. 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.

         21. The participant requires hospitalization or has surgery scheduled during the course of
             the study or has undergone major surgical procedures within 30 days prior to the
             Screening Visit.

         22. The participant has a history of malignancy 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 recovered from cutaneous basal cell carcinoma or
             cervical carcinoma in situ).

         23. The participant has acquired immune deficiency syndrome (AIDS) or human
             immunodeficiency virus (HIV) infection, or tests positive for the hepatitis B surface
             antigen (HBsAg), hepatitis C virus (HCV) antibody, or HCV ribonucleic acid (HCV-RNA).
             However, participants who test positive for 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 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 participants with
                  Gilbert Syndrome)