Clinical trial NCT04531475: Study to Evaluate the Safety and Efficacy of X842 in Patients With Reflux Esophagitis
Official title: A Multicenter, Randomized, Double-blind, Double-simulation, Active Comparator-controlled, Parallel-group Phase II Clinical Study to Evaluate the Efficacy and Safety of X842 Capsules at Different Dosages in Patients With Reflux Esophagitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Reflux Esophagitis
Keywords: X842
Reflux Esophagitis
GERD
PCAB
Lead sponsor: Jiangsu Sinorda Biomedicine Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-08-28
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After completing the relevant laboratory tests and endoscopic examinations at screening, subjects who meet the inclusion criteria and do not meet the exclusion criteria are randomly assigned to X842 capsule low-dose group, X842 capsule high-dose group, and lansoprazole enteric-coated capsule group for 4-week treatment and then receive endoscopy. In the study, the duration of subjects receiving treatment with the test drug or comparator is 4 weeks. If a subject has the reflux esophagitis (RE) uncured under endoscopy at week 4 of treatment, the sponsor will give the subject lansoprazole enteric-coated capsules for free for another 4 weeks' treatment.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to investigate the efficacy and dose-effect relationship of X842 capsules at different dosages in the treatment of reflux esophagitis for 4 weeks in comparison with lansoprazole enteric-coated capsules.

Detailed description: It is designed as a multicenter, randomized, double-blind, double-simulation, high and low dose group, active comparator-controlled, parallel-group study to investigate the efficacy and dose-effect relationship of X842 capsules at different dosages in the treatment of reflux esophagitis for 4 weeks in comparison with lansoprazole enteric-coated capsules.

Eligibility criteria: Inclusion Criteria:

1. Males or females, 18 years ≤ age ≤ 75 years;
2. Within 14 days prior to randomization, the subjects are endoscopically diagnosed with reflux esophagitis from Los Angeles (LA) grade A to D (notes: the percent of the subjects with LA grade A of RE should be no more than 60% of the all subjects who are planned to be enrolled in the study);
3. Subjects fully understand the trial contents, participate in the trial voluntarily, and sign the informed consent forms.

Exclusion criteria:

1. Subjects who receive X842 capsules or other P-CAB drugs in previous clinical studies;
2. Subjects known to be allergic to X842 capsules or lansoprazole enteric-coated capsules, or relevant excipients of X842 capsules or lansoprazole enteric-coated capsules, such as lactose, microcrystalline cellulose, croscarmellose sodium, sodium dodecyl sulfate, sodium stearyl fumarate, and silicon dioxide;
3. Subjects unable to receive upper gastrointestinal endoscopy;
4. Subjects unable to independently complete the subject diary cards;
5. Subjects known to have any concomitant disease that may affect the esophagus (eosinophilic esophagitis, esophageal varices, dermatosclerosis, viral or fungal infectious esophagitis, or esophageal stenosis), or have a history of esophageal radiotherapy or cryotherapy (but subjects are eligible for this study if they have concomitant esophageal hiatal hernia)
6. Subjects known to have a history of Barrett's esophagus, or who have Barrett's esophagus discovered during endoscopy at screening;
7. Subjects who have acute upper gastrointestinal hemorrhage within 4 weeks prior to enrollment;
8. Subjects with active peptic ulcer discovered during upper gastrointestinal endoscopy, or subjects with suspicious or definite malignancies;
9. Subjects known to have Zollinger-Ellison syndrome or inflammatory bowel disease (IBD);
10. Subjects with concomitant cholecystolithiasis, gallbladder wall crystal or gallbladder polyp discovered by B ultrasonography at screening;
11. Subjects with a history of surgery that may affect the esophagus (for example, fundoplication and mechanical distension for esophageal stenosis), or subjects with a history of cholecystectmy or surgery of stomach or duodenum (except endoscopic excision of benign polyps, and except simple suture surgeries such as for gastric perforation);
12. Subjects with a history of malignancies within 5 years prior to screening (a subject can participate in the study if his /her skin basal cell carcinoma or carcinoma in situ of uterine cervix has been cured);
13. Subjects with concomitant serious diseases of central nervous system, cardiovascular system, respiratory system, liver, kidney, gastrointestinal tract, urinary system, endocrine system, or hematological system, and the investigator thinks these diseases may mix the study results up or affect the safety of the subject;
14. Laboratory test results at screening showing that ALT or AST is larger than 1.5 times of the upper limit of normal, or kidney function index Cr is larger than the upper limit of normal (a re-examination is permitted in the study, and subjects will be excluded if they still fail to meet the inclusion criteria);
15. Subjects who use proton pump inhibitors (PPIs), P-CABs, histamine2 receptor antagonists (H2RAs), or gastric mucosal protectors (except hydrotalcite) within 2 weeks prior to randomization;
16. Subjects who chronically use (\>12 doses / month) non-steroidal anti-inflammatory drug (including cyclooxygenase-2 inhibitor), anti-platelet drug (such as aspirin and clopidogrel), or anticoagulant (such as Warfarin) prior to randomization, and can not stop the medication during the trial;
17. At screening, subjects with clinically significant ECG abnormalities, including serious arrhythmia, multifocal preventricular contraction (PVC), grade II or above atrioventricular block, and prolongation of the Q-T interval (QTc≥450 ms in males and QTc≥470 ms in females);
18. Diabetic subjects with poorly controlled blood glucose level (fasting blood glucose (FBG) \> 10.0 mmol/L), or hypertensive subjects with poorly controlled blood pressure (systolic pressure ≥150 mmHg or diastolic pressure ≥100 mmHg);
19. Subjects with known acquired immunodeficiency syndrome (AIDS);
20. Subjects who are using atazanavir sulfate or ripivirin hydrochloride at screening;
21. Subjects with a history of long-term abuse of drug or alcohol within 6 months prior to screening;
22. Female subjects with suspicious or known pregnancy, those in breast-feeding period, or those who are planned to become pregnant during the trial. At the investigator's discretion, women of childbearing age who cannot use a medically-proven and reliable method of contraception from signing the informed consent forms to 4 weeks after the last dose of the study;
23. Subject who plan to have a surgery requiring hospitalization, or subject who need to have a surgery during his/her participation in the study;
24. Subjects who participate in other drug/medical device clinical studies and use the drug/medical device within 3 months prior to randomization;
25. Subjects who are considered unsuitable for participating in this trial by investigators.

Primary outcomes:
measure: Proportion of Subjects Whose Reflux Esophagitis is Cured as Confirmed by Endoscopy at Week 4 of Treatment
timeFrame: 4 weeks
Secondary outcomes:
measure: Proportion of Subjects Whose Reflux Esophagitis LA Grade is Decreased by ≥1 as Confirmed by Endoscopy at Week 4 of Treatment
timeFrame: 4 weeks
measure: Changes in Gerd-Q Score at Week 2 and 4 Compared With the Baseline
timeFrame: Week 2 and Week 4
measure: Changes in Serum Gastrin at Week 2 and 4 of Treatment Compared with the Baseline
timeFrame: Week 2 and Week 4
measure: Measurement of the PK Profile
timeFrame: Week 2 and Week 4
measure: Number of Subjects Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to 6 weeks
measure: Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of blood serum
timeFrame: Up to 6 weeks
measure: Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of blood
timeFrame: Up to 6 weeks
measure: Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of urine
timeFrame: Up to 6 weeks
measure: Number of Subjects With Markedly Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to 6 weeks
measure: Vital signs of body temperature
timeFrame: Up to 6 weeks
measure: Vital signs of blood pressure
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Liu'an
country: China
facility: Liuan People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Luhe Hospital Capital Medical University
state: Beijing
city: Guiyang
country: China
facility: The Affiliated Hospital of Guzihou Medical University
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Chenzhou
country: China
facility: Affiliated Hospital of Xiangnan University
state: Hunan
city: Changzhou
country: China
facility: The First people's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Pingxiang
country: China
facility: Jiangxi PingXiang People's Hospital
state: Jiangxi
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
state: Shanghai
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqi Medical University
state: Sichuan
city: Taizhou
country: China
facility: Taizhou Municipal Hospital
state: Zhejiang
Study officials:
affiliation: Jiangsu Sinorda Biomedicine Co., Ltd
name: Pingsheng Hu, Ph.D
role: STUDY_CHAIR
References: