A Randomized Double-blind, Double Dummy, Active Comparator-controlled Dose-finding Study in Patients With Erosive Esophagitis Due to Gastro-esophageal Reflux Disease (GERD) Los Angeles Grade C or D, and Patients With at Least Partial Symptom Response But Endoscopically Still Unhealed After 8 Weeks History of Standard Treatment Healing Course With Proton-pump Inhibitor (PPI), to Investigate Safety, Tolerability, and Healing Rates After 4 Weeks Treatment of X842 or Lansoprazole, and Symptom Pattern During Subsequent 4 Weeks Treatment With Lansoprazole
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 248
- 试验地点
- 79
- 主要终点
- Number of Patients With Esophageal Mucosa Healing
研究概览
简要总结
This study will be conducted in patients with erosive esophagitis due to gastro-esophageal reflux disease (GERD) Los Angeles (LA) grades C or D, and in patients with at least partial symptom response but still endoscopically unhealed (LA grades A or B) after 8 weeks history of standard treatment healing course with PPI, designed to support dose selection for Phase 3 and to investigate safety, tolerability, and healing rates after 4 weeks treatment of X842 or Lansoprazole, and symptom pattern during subsequent 4 weeks treatment with Lansoprazole.
详细描述
This is a randomized, double-blind, active comparator-controlled study with a parallel-group design including four arms with X842 and one arm with Lansoprazole.
Randomization to one of the treatments with X842 twice daily (BID) 25 mg, 50 mg, 75 mg, 100 mg, or Lansoprazole 30 mg once daily (QD) will be based on a 1:1:1:1:1 scheme.
The duration of each patient's participation in the study, including screening, blind treatment period, and open-label treatment period will be approximately 60 days. The patients will be randomized for 4 weeks of double-blind treatment and will be provided with investigational medicinal product for 35 days.
All patients will have an endoscopic evaluation after 4 weeks of treatment. Following the endoscopic evaluation, all patients will receive subsequent 4 weeks of open-label treatment with Lansoprazole. Repeated symptom evaluation to detect symptom patterns will be assessed during this period.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index (BMI) ≥ 18 and ≤ 40 kg/m^2 at screening.
- •Gastro-esophageal reflux disease with endoscopically confirmed esophagitis:
- •LA grade C or D ≤7 days before randomization (with or without historical PPI treatment) or
- •LA grade A or B ≤7 days before randomization and history of treatment with the standard healing course of PPI for minimum of 8 weeks prior to screening and ≤7 days of non-treatment during this period and at least partial symptom response during the minimum of 8 weeks of PPI treatment.
- •Willing and able to comply with all aspects of the protocol (including capsule swallowing, diary completion, etc.).
- •Capable of signing informed consent form.
排除标准
- •History or presence of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disease or disorder.
- •Patients with so-called "alarm features" in symptomatology, like odynophagia, severe dysphagia, bleeding, weight loss, anemia, and blood in stool pointing to a possible malignant disease of the gastrointestinal (GI) tract.
- •Present clinically significant psychiatric diagnosis.
- •History of malignancy of any organ system.
- •Presence of esophageal ulcer, stricture, Barrett´s esophagus or suspected esophagitis secondary to infection, inflammatory disease, ingestion of erosive chemicals or history of any surgical or medical condition which might significantly alter the Gastro-oesophageal reflux disease (GERD) status or the absorption, distribution, metabolism or excretion of drugs.
- •Known severe atrophic gastritis.
- •Any planned major surgery within the duration of the study.
- •History of a positive result for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B core antigen (anti-HBcAg), or antibody to Hepatitis C virus (anti-HCV) or presence of these findings on screening.
- •History of long QTc syndrome (e.g. QTc ≥450 ms for males and ≥470 ms for females).
- •Cardiac arrhythmias or any clinically significant abnormalities in the resting 12-lead ECG at the time of screening, as judged by the Investigator.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
- •Current or history of alcohol, drug abuse and/or use of anabolic steroids within 2 years prior to screening.
- •Women who are pregnant or breastfeeding.
- •Patients who have previously participated (completed or withdrawn) in this study CX842A2201.
研究组 & 干预措施
X842 50 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 Dummy (Drug)
Lansoprazole
Patients will receive 2 tablets (X842 dummy×2) and 1 capsule (Lansoprazole 30 mg) in the morning, and 2 tablets (X842 dummy×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 Dummy (Drug)
X842 75 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 25 mg) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 25 mg) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole Dummy (Drug)
X842 25 mg BID
Patients will receive 2 tablets (X842 25mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 25 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 (Drug)
X842 25 mg BID
Patients will receive 2 tablets (X842 25mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 25 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 Dummy (Drug)
X842 25 mg BID
Patients will receive 2 tablets (X842 25mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 25 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole (Drug)
X842 25 mg BID
Patients will receive 2 tablets (X842 25mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 25 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole Dummy (Drug)
X842 50 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 (Drug)
X842 50 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole (Drug)
X842 50 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole Dummy (Drug)
X842 75 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 25 mg) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 25 mg) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 (Drug)
X842 75 mg BID
Patients will receive 2 tablets (X842 50 mg + X842 25 mg) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 25 mg) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole (Drug)
X842 100 mg BID
Patients will receive 2 tablets (X842 50 mg×2) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: X842 (Drug)
X842 100 mg BID
Patients will receive 2 tablets (X842 50 mg×2) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole (Drug)
X842 100 mg BID
Patients will receive 2 tablets (X842 50 mg×2) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole Dummy (Drug)
Lansoprazole
Patients will receive 2 tablets (X842 dummy×2) and 1 capsule (Lansoprazole 30 mg) in the morning, and 2 tablets (X842 dummy×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.
干预措施: Lansoprazole (Drug)
结局指标
主要结局
Number of Patients With Esophageal Mucosa Healing
时间窗: Week 4
The healing of erosive esophagitis due to gastro-esophageal reflux disease (GERD) was assessed. It supported the dose selection X842,through the assessment of healing of erosive esophagitis due to GERD based on endoscopic assessment after 4 weeks of treatment. The dose that would lead to having 85% of the patients have esophageal mucosa healing after 4 weeks of treatment. Following the endoscopic evaluation, all patients received subsequent 4 weeks of open-label treatment with lansoprazole. Repeated symptom evaluation was assessed during this period to detect the symptom pattern. Endoscopy evaluation at 4 weeks was based on the level and duration of acid control achieved with X842. Symptom evaluation was assessed using the validated patient-reported outcome (PRO) QOLRAD (Heartburn version) and patient diaries (RESQ-eDiary).
次要结局
- Number of Patients With Adverse Events (AEs)(From Screening (Day -7 to Day 0) until Week 8)
- Percentage of Heartburn-Free 24-hour Days(Weeks 1 and 8)
- Percentage at Most-mild Heartburn 24-hour Days(Weeks 1 and 8)
- Investigator Assessment of Symptoms by Frequency and Severity(Weeks 1 and 8)
- Change From Baseline in Quality of Life in Reflux and Dyspepsia (QOLRAD) Score(Baseline, Weeks 1, and 8)