Efficacy and Safety of Vonoprazan Compared to Lansoprazole in the Maintenance Treatment of Erosive Esophagitis
Condition: Erosive Esophagitis
MeSH terms: Esophagitis
Intervention: Vonoprazan; Lansoprazole; Vonoprazan Placebo; Lansoprazole Placebo
Intervention description: Vonoprazan tablets; Lansoprazole capsules or tablets; 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: 703.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      This is a comparative study of vonoprazan (TAK-438) (10 mg or 20 mg) in participants in whom
      endoscopic healing of erosive esophagitis has been confirmed with vonoprazan or adequate
      treatment with a proton pump inhibitor (PPI), to demonstrate the non-inferiority of
      vonoprazan to lansoprazole in their maintenance treatment (6 months or 24 weeks) as well as
      to determine the clinically recommended dose for vonoprazan for maintenance therapy in
      erosive esophagitis.
    

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 on endoscopy to have had erosive esophagitis [Los Angeles (LA)
             classification grades A to D] within 84 days of Day 1.

          4. If the participant is not rolled over from TAK-438_303 study, he/she has undergone an
             open-label Proton pump inhibitor (PPI) treatment (Lansoprazole 30 mg, once daily) of 4
             or 8 weeks within the TAK-438_305 protocol.

          5. Has been confirmed on endoscopy to have healing of erosive esophagitis. This
             endoscopy, if not part of the TAK-438_303 study, must have been within the last 14
             days prior to randomization, otherwise the endoscopy must be repeated to confirm
             healing before randomization in the TAK-438_305 study.

          6. 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 temporarily admitted for
             examination.

          7. 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 and for 4 weeks after last
             dose of study medication.

        Exclusion Criteria:

          1. Has received any investigational compound (other than study TAK-438_303) within 84
             days prior to screening phase.

          2. Has received TAK-438 in a previous clinical study (other than study TAK-438_303) or as
             a therapeutic agent.

          3. 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. 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 significant central nervous system (CNS),
             cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological,
             endocrine or hematological disease.

          6. Has a history of hypersensitivity or allergies to TAK-438 or to proton pump inhibitors
             (PPIs) including any associated excipients.

          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 start the screening phase.

          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 (other than study TAK-438_303) 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 Screening Phase (Visit 1) (with the possible inclusion of
             those with gastric or duodenal erosion). Participants requiring non-steroidal
             anti-inflammatory drugs (NSAIDs) or aspirin treatment along with the concomitant PPI
             therapy to prevent gastrointestinal (GI) bleeding should not be enrolled.

         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 Screening 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] 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 on 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).