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The Phase III Clinical Trial of X842 Capsules for Reflux Esophagitis

Not Applicable
Completed
Conditions
Reflux Esophagitis
Interventions
Registration Number
NCT07079540
Lead Sponsor
Jiangsu Sinorda Biomedicine Co., Ltd
Brief Summary

To evaluate the efficacy and safety of X842 Capsules 50 mg compared to Lansoprazole Enteric Capsules for the treatment of reflux esophagitis, and to characterize the population pharmacokinetics of X842 capsules in this patient population.

Detailed Description

This study uses a multicenter, randomized, double-blind, double-dummy, active-controlled parallel-group, non-inferiority design to compare the efficacy and safety of X842 capsules (50 mg) in the treatment of reflux esophagitis over 4 to 8 weeks in comparison with lansoprazole enteric-coated capsules(30 mg) . Additionally, the population pharmacokinetics characteristics of X842 capsules in patients with reflux esophagitis is observed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
380
Inclusion Criteria
  1. Males or females, 18 years ≤ age ≤ 75 years;
  2. Within 7 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 20% of the all subjects who are planned to be enrolled in the study);
  3. Subjects who can independently complete the subject diary cards;
  4. 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. Endoscopic examination revealed concomitant diseases potentially affecting the esophagus, excluding hiatal hernia, and excluding Barrett's esophagus with metaplastic columnar epithelium that either does not involve the entire esophageal circumference or is short-segment (< 3 cm in length).
  5. Patients with rheumatic/autoimmune diseases potentially affecting esophageal motility (e.g., scleroderma, undifferentiated connective tissue disease), or those with a history of esophageal radiotherapy or cryotherapy;
  6. Subjects who have acute upper gastrointestinal hemorrhage within 4 weeks prior to enrollment;
  7. Subjects with active peptic ulcer discovered during upper gastrointestinal endoscopy, or subjects with suspicious or definite malignancies;
  8. Subjects known to have Zollinger-Ellison syndrome or inflammatory bowel disease (IBD);
  9. Subjects with history of surgery affecting the structure or function of the esophagus, stomach, or duodenum, or surgery altering gastric acid secretion.
  10. Subjects who plan to undergo surgical procedures during the study period that may alter gastric acid secretion (e.g., abdominal surgery, vagotomy, or craniectomy).
  11. 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);
  12. 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;
  13. 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);
  14. Subjects who use of therapeutic doses of GERD medications within 7 days prior to randomization, eg. proton pump inhibitors (PPIs), P-CABs, histamine2 receptor antagonists (H2RAs), or gastric mucosal protectors (except hydrotalcite), prokinetic drugs, and traditional Chinese medicines;
  15. Subjects who chronically use 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;
  16. At screening, subjects with clinically significant ECG abnormalities, including serious arrhythmia, multifocal ventricular premature complexes, grade II or above atrioventricular block, and prolongation of the Q-Tc interval (QTc≥450 ms in males and QTc≥470 ms in females);
  17. Subjects who are using atazanavir sulfate or ripivirin hydrochloride at screening;
  18. Subjects with a history of long-term abuse of drug or alcohol within 6 months prior to screening;
  19. Female subjects with 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;
  20. Subjects who participate in other drug/medical device clinical studies and use the drug/medical device within 3 months prior to randomization;
  21. Subjects who are considered unsuitable for participating in this trial by investigators.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
X842 50mg QDX842X842 50 mg, capsule, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily up to 4 to 8 weeks.
lansoprazole 30mg QDX842 PlaceboLansoprazole 30 mg, capsule, orally, once daily and X842 placebo-matching capsule, orally, once daily up to 4 weeks.
X842 50mg QDLansoprazole PlaceboX842 50 mg, capsule, orally, once daily and lansoprazole placebo-matching capsule, orally, once daily up to 4 to 8 weeks.
lansoprazole 30mg QDLansoprazoleLansoprazole 30 mg, capsule, orally, once daily and X842 placebo-matching capsule, orally, once daily up to 4 weeks.
Primary Outcome Measures
NameTimeMethod
Proportion of Subjects Whose Reflux Esophagitis is Cured as Confirmed by Endoscopy at Week 88 weeks

Healing of reflux esophagitis is defined as endoscopic confirmation of resolved esophagitis (absence of esophageal mucosal breaks) in subjects.

Secondary Outcome Measures
NameTimeMethod
Proportion of Subjects Whose Reflux Esophagitis is Cured as Confirmed by Endoscopy at Week 44 weeks

Healing of reflux esophagitis is defined as endoscopic confirmation of resolved esophagitis (absence of esophageal mucosal breaks) in subjects.

Improvement rate in the frequency and severity of individual clinical symptoms (heartburn, regurgitation) of reflux esophagitis at Weeks 2, 4, and 8 after treatment initiation.2,4,8 weeks

Improvement in the frequency of clinical symptom occurrence: Defined as subjects whose symptom frequency score before treatment was ≥1 point had a reduction of ≥1 point after treatment compared to before treatment.

Improvement in the severity of clinical symptoms: Defined as a reduction of ≥1 point in the symptom severity score of subjects with a score of ≥1 point before treatment after treatment compared to before treatment.

Overall symptomatic resolution rate for reflux esophagitis at Weeks 2, 4, and 82,4,8 weeks

Overall Clinical Symptom Resolution: Defined as the achievement of a score of 0 (i.e., complete disappearance) for all symptoms of reflux esophagitis in subjects with any individual symptom score ≥1 at baseline.

Change in serum gastrin levels from baseline at Weeks 4 and 8 of treatment4, 8 weeks

Serum gastrin testing will be conducted at the central laboratory. The change between the serum gastrin values collected at Weeks 4 and 8 relative to baseline.

Response rates for individual symptom domains (heartburn, regurgitation) in reflux esophagitis at Weeks 2, 4, and 8 post-baseline.2.4.8 weeks

Resolution of individual clinical symptoms: defined as the achievement of score 0 in both severity and frequency for symptoms with baseline scores ≥1.

Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of bloodup to 8 weeks

Number of subjects with any markedly abnormal values in laboratory tests of blood collected throughout study is reported.

Number of Subjects With Markedly Abnormal Electrocardiogram (ECG) Findingsup to 8 weeks

The investigator or the sub-investigator interpreted the ECG using one of the following categories: "within normal limits", "abnormal but not clinically significant", or "abnormal and clinically significant"

Vital signsup to 8 weeks

Blood pressure, respiration, heart rate and body temperature were evaluated at each visit during the screening period and the double-blind treatment period

Pharmacokinetic evaluationup to 8 weeks

Quantification of plasma concentrations of X842 and its metabolites to characterize the population pharmacokinetic profile of X842 capsules in GERD patients.

Number of Subjects Reporting Who Had One or More Treatment-emergent Adverse Event (TEAE)up to 8 weeks

Adverse event is defined as any adverse medical event that is observed in a subject who is receiving a drug treatment or in a clinical study, and that does not necessarily have a causal relationship with the treatment.

Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of blood serum Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of blood serumup to 8 weeks

Number of subjects with any markedly abnormal values in laboratory tests of blood serum collected throughout study is reported.

Number of Subjects With Markedly Abnormal Clinical Laboratory assessment of urineup to 8 weeks

Number of subjects with any markedly abnormal values in laboratory tests of urine collected throughout study is reported.collected throughout study is reported.

Trial Locations

Locations (53)

Liuan People's Hospital

🇨🇳

Liu'an, Anhui, China

Xuancheng People's Hospital

🇨🇳

Xuancheng, Anhui, China

The 900th Hospital of the Joint Logistic Support Force of the People's Liberation Army of China

🇨🇳

Fuzhou, Fujian, China

The First Hospital of Lanzhou University

🇨🇳

Lanzhou, Gansu, China

Nanfang Hospital, Southern Medical University

🇨🇳

Guangzhou, Guangdong, China

Huizhou Central People's Hospital

🇨🇳

Huizhou, Guangdong, China

Jiangmen Central Hospital

🇨🇳

Jiangmen, Guangdong, China

Meizhou People's Hospital

🇨🇳

Meizhou, Guangdong, China

Peking University Shenzhen Hospital

🇨🇳

Shenzhen, Guangdong, China

Liuzhou Worker's Hospital

🇨🇳

Liuzhou, Guangxi, China

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Liuan People's Hospital
🇨🇳Liu'an, Anhui, China

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