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)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 208
- 试验地点
- 36
- 主要终点
- Number of Participants With Foveolar Hyperplasia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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
研究组 & 干预措施
Vonoprazan group
Vonoprazan 20 mg administered orally once daily in the healing phase + vonoprazan 10 mg (as the initial dose and adjusted to vonoprazan 10 mg or 20 mg) administered orally once daily in the maintenance phase
干预措施: Vonoprazan (Drug)
Lansoprazole group
Lansoprazole 30 mg administered orally once daily in the healing phase + lansoprazole 15 mg (as the initial dose and adjusted to lansoprazole 15 mg or 30 mg) administered orally once daily in the maintenance phase
干预措施: Lansoprazole (Drug)
结局指标
主要结局
Number of Participants With Foveolar Hyperplasia
时间窗: 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.
Number of Participants With Enterochromaffin-like-cell Hyperplasia
时间窗: 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.
Number of Participants With Malignant Alteration of Epithelial Cells
时间窗: 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.
Number of Participants With G-cell Hyperplasia
时间窗: 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.
Number of Participants With Parietal Cell Protrusion/Hyperplasia
时间窗: 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.
次要结局
- Number of Participants With Cobblestone Mucosa(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Multiple White and Flat Elevated Lesions(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Atrophy in Greater Curvature of Antrum(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Neutrophilic Infiltration in Greater Curvature of Middle Gastric Body(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Middle Gastric Body(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Intestinal Metaplasia in Greater Curvature of Antrum(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) in Maintenance Phase(260 weeks (Baseline, up to the end of Maintenance Phase))
- Number of Participants With Hyperplastic Polyp(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Presence of H.Pylori in Greater Curvature of Middle Gastric Body(Up to Week 268 (Week 260 in Maintenance Phase))
- Percentage of Participants With Recurrence of Erosive Esophagitis (EE)(Up to Week 268 (Week 260 in Maintenance Phase))
- Percentage of Participants Who Healed EE at the End of Healing Phase(Up to Week 8)
- Number of Participants With Fundic Gland Polyp(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Black Spots(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Antrum(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Neutrophilic Infiltration in Greater Curvature of Antrum(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Atrophy in Greater Curvature of Middle Gastric Body(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Gastric Polyp(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Intestinal Metaplasia in Greater Curvature of Middle Gastric Body(Up to Week 268 (Week 260 in Maintenance Phase))
- Number of Participants With Presence of H.Pylori in Greater Curvature of Antrum(Up to Week 268 (Week 260 in Maintenance Phase))