Efficacy and Safety of Oral Once-Daily Vonoprazan (TAK-438) in Participants With Erosive Esophagitis
Condition: Erosive Esophagitis
MeSH terms: Esophagitis
Intervention: Vonoprazan; Lansoprazole; Vonoprazan Placebo; Lansoprazole Placebo
Intervention description: Vonoprazan tablets; Lansoprazole capsules; Vonoprazan placebo-matching tablets; Lansoprazole placebo-matching capsules
Intervention MeSH terms: Lansoprazole; Dexlansoprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 481.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of the study is to demonstrate the efficacy of vonoprazan (TAK-438) versus
      lansoprazole in the treatment of erosive esophagitis classified as Los Angeles (LA)
      classification grades A to D at Week 8.
    

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 or, when applicable, the participant's legally acceptable
             representative signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures.

          3. Has been confirmed in an endoscopy to have erosive esophagitis, ie, the Los Angeles
             (LA) classification grades A to D within 7 days of the start of the Day 1 (Visit 2).

             Note: The recruitment goal is to ensure that those with LA classification grade C/D
             will account for more than 30% of all participants enrolled (144/480), with no further
             recruitment of those with grade A/B considered when they account for more than 70%
             (336/480) of all participants.

          4. Is aged 18 years old or older (or the local age of consent if that is older), male or
             female, at the time of signing an informed consent, and is being treated on an
             outpatient basis for erosive esophagitis, including those admitted temporarily for
             examination.

          5. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agrees to use routinely adequate contraception from signing
             of informed consent throughout the duration of the study.

        Exclusion Criteria:

          1. Has received any investigational compound within 84 days prior to the start of the
             Observation phase.

          2. Has received TAK-438 in a previous clinical study or as a therapeutic agent.

          3. Is an immediate family member, study site employee, or is in a dependant 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. Has, in the judgment of the investigator, clinically significant abnormal
             hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening.

          5. Has a history or clinical manifestations of serious central nerve system (CNS),
             cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological,
             endocrine or hematological disease.

          6. Has a history of hypersensitivity or allergies to TAK-438 (including its excipients*)
             or to proton pump inhibitors (PPIs).

             *D-mannitol, crystalline cellulose, hydroxypropyl cellulose, fumaric acid,
             croscarmellose sodium, magnesium stearate, hypromellose, macrogol 6000, titanium
             oxide, yellow iron sesquioxide and iron sesquioxide.

          7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse within 1 year prior to the Observation Phase (Visit 1).

          8. Is required to take excluded medications.

          9. If female, the participant is pregnant or lactating or intending to become pregnant
             before, during, or within 1 month after participating in this study; or intending to
             donate ova during such time period.

         10. Has participated in another clinical study within the past 30 days from Visit 1.

         11. Has co-morbidities that could affect the esophagus (eosinophilic esophagitis,
             esophageal varices, scleroderma, viral or fungal infection, esophageal strictures), a
             history of radiotherapy or cryotherapy for the esophagus; those with corrosive or
             physiochemical injury (with the possible inclusion in the study of those with
             Schatzki's ring or Barrett's esophagus).

         12. Has a history of surgical procedures that may affect the esophagus (eg, fundoplication
             and mechanical dilatation for esophageal strictures excluding Schatzki's ring) or a
             history of gastric or duodenal surgery excluding endoscopic removal of benign polyps.

         13. Developed acute upper gastrointestinal bleeding, gastric ulcer (a mucosal defect with
             white coating) or duodenal ulcer (a mucosal defect with white coating), within 30 days
             before the start of the Observation Phase (Visit 1) (with the possible inclusion of
             those with gastric or duodenal erosion).

         14. Has Zollinger-Ellison syndrome or gastric acid hypersecretion or a history of gastric
             acid hypersecretion.

         15. Is scheduled for surgery that requires hospitalization or requires surgical treatment
             during his/her participation in the study.

         16. Has a history of malignancy or was treated for malignancy within 5 years before the
             start of the Observation Phase (Visit 1) (the participant may be included in the study
             if he/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ).

         17. Has acquired immunodeficiency syndrome (AIDS) or hepatitis, including hepatitis virus
             carriers: hepatitis B surface antigen (HBsAg) positive, or hepatitis C virus
             (HCV)-antibody-positive (the participant may be included in the study if he/she is
             HCV-antigen or HCV-ribonucleic acid [RNA]-negative).

         18. Laboratory tests performed at the start of the Early Observation Phase (visit 1)
             revealed any of the following abnormalities in the participant:

               1. Creatinine levels: >2 mg/dL (>177 μmol/L).

               2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or total
                  bilirubin levels: > upper limit of normal (ULN).

         19. Is active in the Screening Period after the closure of enrollment identified by the
             Sponsor or the number of participants randomized with LA classification A/B or C/D
             have reached the required sample size.