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Completed

NCT Number: NCT02679508

Vonoprazan Study in Patients With Erosive Esophagitis to Evaluate Long-term Safety

The purpose of this study is exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration (260 weeks: 5 years) of vonoprazan 10 mg or 20 mg in patients receiving maintenance treatment after healed erosive esophagitis (EE), and the curative effect of vonoprazan 20 mg versus lansoprazole in patients with EE.

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Key information

Conditions

Erosive Esophagitis Digestive System Diseases Esophageal Diseases Esophagitis Gastroenteritis Gastrointestinal Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Tokatsu Tsujinaka Hospital, Abiko, Chiba, Japan

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About this study

This is a multicenter, open-label, randomized, parallel-group study to exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration of vonoprazan in maintenance treatment after healed EE, and the curative effect of vonoprazan versus lansoprazole in participants with EE.

Participants endoscopically diagnosed with EE of Los Angeles (LA) Classification Grades A to D at the start of treatment (Week 0 of the healing phase) will be randomly assigned to receive either vonoprazan 20 mg or lansoprazole 30 mg to be taken once daily for up to 8 weeks. Subjects with healed EE as confirmed endoscopically at Week 4 or 8 in the healing phase will enter the maintenance phase.

In the maintenance phase, the vonoprazan group and the lansoprazole group will be administered a starting dose of 10 mg and 15 mg, respectively, once daily up to 260 weeks.

If the principal investigator or investigator judged the effect of vonoprazan 10 mg or lansoprazole 15 mg to be insufficient as the maintenance treatment of EE, vonoprazan and lansoprazole may be increased to 20 mg and 30 mg, respectively.

The research period will consist of two subperiods: healing phase in which participants with EE will receive treatment (for 4 or 8 weeks) and maintenance phase in which participants will receive maintenance treatment (for 260 weeks), and thus, a total of up to 268 weeks. The number of visits will be a maximum of 18 visits. Planned number of research subjects, as the number of research subjects for entry to the maintenance phase, will be 130 participants in the vonoprazan group and 65 participants in the lansoprazole group.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Healing Phase:

  • Participants endoscopically diagnosed with EE of grades A to D by the LA Classification Grading System at the start of treatment (Week 0 of the healing phase)
  • Participants with H. pylori negative
  • Participants who, in the opinion of the principal investigator or investigator, are capable of understanding the content of the clinical research and complying with the research protocol requirements.
  • Participants who can sign and date an informed consent form and information sheet prior to the conduction of the clinical research procedures.
  • Male or female participants aged 20 years or older at the time of informed consent
  • Therapeutic category: Ambulatory

Maintenance Phase:

  • Participants who have endoscopically confirmed EE healing* (mucous membrane disorder is not observed) at completion of the healing phase (Week 4 or 8 of the healing phase)
  • Participants who are classified as grade 0 according to severity classification of EE (See Table 9.b)
  • Participants who have been determined to be appropriate as subjects for maintenance treatment of EE by the principal investigator or investigator

Exclusion criteria

Healing Phase:

  • Participants with concurrent peptic ulcer (except scarred stage) or Zollinger-Ellison syndrome
  • Participants who received treatment with PPIs (including vonoprazan) within 4 weeks (Week -4 to Week 0) prior to the start of healing phase (Week 0 of the healing phase)
  • Participants with a history of H. pylori eradication.
  • Participants who have received surgery or treatment affecting gastroesophageal reflux (fundoplication or dilation for esophageal stenosis [excluding Schatzki's ring], etc.)
  • Participants with an esophagus-related complication (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal stenosis, etc.), a history of radiotherapy or cryotherapy of the esophagus, a caustic or physiochemical trauma (esophageal sclerotherapy, etc.). However, participants with Schatzki's ring (mucosal tissue ring around inferior esophageal sphincter) or Barrett's esophagus are allowed to be included.
  • Participants with clinically apparent hepatic impairment (e.g., AST or ALT levels at the time of informed consent: >1.5 times the upper limit of normal (ULN).
  • Participants with renal impairment or renal failure [creatinine clearance (CCr) ˂30 mL/min, etc.]
  • Participants with a history of hypersensitivity or allergy for PPIs.
  • Participants with a history of gastrectomy, gastrointestinal resection, or vagotomy
  • Participants with a malignant tumor
  • Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant
  • Participants with one of the diseases listed under administration contraindication in the vonoprazan or lansoprazole package insert
  • Participants planning to take prohibited concomitant medications during the research period
  • Participants participating in other clinical studies
  • Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

Maintenance Phase:

  • Participants who have taken PPIs other than the study drug or the control drug during the healing phase
  • Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

Treatment and study plan

Vonoprazan

Drug

Vonoprazan fumarate 10 mg or 20 mg capsules

Lansoprazole

Drug

Lansoprazole 15 mg or 30 mg capsules

Primary outcomes

  1. Number of Participants With Malignant Alteration of Epithelial Cells

    Time frame: Time Frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with malignant alteration of epithelial cells for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

  2. Number of Participants With Parietal Cell Protrusion/Hyperplasia

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with parietal cell protrusion/hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

  3. Number of Participants With Foveolar Hyperplasia

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with foveolar hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

  4. Number of Participants With Enterochromaffin-like-cell Hyperplasia

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with enterochromaffin-like-cell hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

  5. Number of Participants With G-cell Hyperplasia

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with G-cell hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

Secondary outcomes

  1. Percentage of Participants With Recurrence of Erosive Esophagitis (EE)

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Erosive esophagitis recurrence is defined as endoscopically confirmed to have erosive esophagitis (LA classification grades O and A to D) during the Maintenance Phase. The LA classification graded as follows- Grade O: normal mucosa; Grade A: nonconfluent mucosal breaks <5 mm in length; Grade B: nonconfluent mucosal breaks ≥ 5mm in length; Grade C: confluent mucosal breaks <75% circumferential; Grade D: confluent mucosal breaks >75% circumferential.

  2. Percentage of Participants Who Healed EE at the End of Healing Phase

    Time frame: Up to Week 8

    Percentage of participants who healed EE at the end of healing phase was reported.

  3. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) in Maintenance Phase

    Time frame: 260 weeks (Baseline, up to the end of Maintenance Phase)

    Number of participants reporting one or more TEAEs in Maintenance Phase was reported. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

  4. Number of Participants With Fundic Gland Polyp

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with fundic gland polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

  5. Number of Participants With Hyperplastic Polyp

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with hyperplastic polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

  6. Number of Participants With Cobblestone Mucosa

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with cobblestone mucosa for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

  7. Number of Participants With Multiple White and Flat Elevated Lesions

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with multiple white and flat elevated lesions for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

  8. Number of Participants With Black Spots

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with black spots for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

  9. Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Middle Gastric Body

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with inflammation (mononuclear infiltration) in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  10. Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Antrum

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with inflammation (mononuclear infiltration) in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  11. Number of Participants With Neutrophilic Infiltration in Greater Curvature of Middle Gastric Body

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with neutrophilic infiltration in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  12. Number of Participants With Neutrophilic Infiltration in Greater Curvature of Antrum

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with neutrophilic infiltration in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  13. Number of Participants With Atrophy in Greater Curvature of Middle Gastric Body

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with atrophy in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  14. Number of Participants With Atrophy in Greater Curvature of Antrum

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with atrophy in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  15. Number of Participants With Intestinal Metaplasia in Greater Curvature of Middle Gastric Body

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with intestinal metaplasia in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  16. Number of Participants With Intestinal Metaplasia in Greater Curvature of Antrum

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with intestinal metaplasia in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  17. Number of Participants With Presence of H.Pylori in Greater Curvature of Middle Gastric Body

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with presence of H.pylori in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  18. Number of Participants With Presence of H.Pylori in Greater Curvature of Antrum

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with presence of H.pylori in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

  19. Number of Participants With Gastric Polyp

    Time frame: Up to Week 268 (Week 260 in Maintenance Phase)

    Numbers of participants with gastric polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported. The number analyzed is the number of participants with data available for analysis.

Sponsors and collaborators

Lead sponsor

Takeda

Industry

Registry information

Official study title

Vonoprazan Study In Patients With Erosive Esophagitis to Evaluate Long-term Safety: A Study to Evaluate the Safety of Long-term Administration of Vonoprazan in Maintenance Treatment in Patients With Erosive Esophagitis (EE)

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Feb 10, 2016
Registry last updated
Dec 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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