A Study of Anaprazole Sodium Enteric-coated Tablets in the Treatment of Reflux Esophagitis

A Multicenter, Randomized, Double-blind, Double-dummy, Positive Drug Parallel Controlled Phase II Clinical Trial to Evaluate Efficacy and Safety of Anaprazole Sodium Enteric-coated Tablets in the Treatment of Reflux Esophagitis

A phase 2, randomized, double-blind, double-dummy, positive drug parallel controlled, multicenter trial to evaluate efficacy and safety of within 8 weeks (including 8 weeks) treatment of Anaprazole 40mg QD, 60mg QD compared with Rabeprazole 20mg QD in patients with reflux esophagitis.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastrointestinal Diseases; Gastroesophageal Reflux; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Reflux Esophagitis
• Intervention / Treatment: Drug: Anaprazole sodium 40 mg; Drug: Anaprazole sodium 60 mg; Drug: Rabeprazole sodium 20 mg

Detailed Description

This is a multicenter, randomized, double-blind, double-dummy, active drug-parallel-controlled, phase 2 clinical study to evaluate the efficacy and safety of Anaprazole Sodium 40 mg QD and 60 mg QD versus Rabeprazole Sodium 20 mg QD in the treatment of reflux esophagitis in Chinese subjects with reflux esophagitis. The target population for this study was subjects with endoscopically confirmed reflux esophagitis. All potential participants will provide informed consent, and those who provide informed consent will enter the Screening Period (Day -7 to Day -1) and be assessed for screening eligibility according to the inclusion and exclusion criteria. The study is expected to enroll approximately 156 subjects with reflux esophagitis (LA classification grades A-D) who meet enrollment criteria (and none of the exclusion criteria), and eligible subjects will be randomized into 3 groups (Anaprazole Sodium 40 mg QD, 60 mg QD, and Rabeprazole Sodium 20 mg QD) in a 1:1: 1 ratio according to a predefined randomization table, with 52 subjects in each group. All subjects take the corresponding study drug within 30-60 minutes before breakfast for 4 or 8 consecutive weeks (subjects were followed up at Week 4 of treatment, and if the subject'endoscopy indicated that the reflux esophagitis was healed, the healed subject ended study treatment and entered safety follow-up. Subjects who were not cured were to continue treatment until 8 weeks if endoscopy at 4 weeks of treatment indicated that reflux esophagitis was not cured.). All subjects complete treatment at 4 or 8 weeks of treatment and were followed for safety. At the end of the study, statistical analysis will be performed on the efficacy and safety indicators of the study drug to compare the efficacy and safety of Anaprazole sodium and rabeprazole sodium in the treatment of reflux esophagitis. Participants will primarily be assessed for the cure rate of reflux esophagitis based on endoscopy of 3 groups. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yaping Luo; Phone Number: 15367827140; Email: luoyaping@xuanzhubio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Changhai Hospital
      • Contact: Zhaoshen Li; Phone Number: 021-55621735; Email: zhaoshen-li@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects clearly understand and voluntarily participate in this study, sign the informed consent form and voluntarily comply with the study procedures;
2. Age ≥ 18 years and ≤ 70 years, male or female;
3. Endoscopic diagnosis of reflux esophagitis (LA classification criteria grades A-D) within 7 days prior to randomization.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be allowed to participate in this study:

Past medical history

1. Subjects whose primary diseases that are not suitable for participating in the clinical trial cannot be effectively controlled in the investigator 's opinion, such as patients with previous severe heart, brain, lung, liver, kidney and other systemic diseases;
2. Patients with previous concomitant diseases that may affect esophageal motility or motility, which may still affect the efficacy evaluation (e.g., eosinophilic esophagitis, esophageal varices, scleroderma, viral infection or fungal infection, esophageal stenosis, etc.) at the investigator 's discretion, or with a history of esophageal radiotherapy or esophageal cryotherapy;
3. History of previous surgical procedures that could affect the esophagus (eg, fundoplication and mechanical dilatation for esophageal strictures), or history of gastric or duodenal surgery, excluding endoscopic removal of benign polyps;
4. Subjects with active peptic ulcer, active upper/lower gastrointestinal bleeding confirmed by esophagogastroduodenoscopy (EGD) within 30 days prior to randomization;
5. Subjects with previous Zollinger-Ellison syndrome, achalasia, secondary esophageal motility disorder, irritable bowel syndrome, inflammatory bowel disease;
6. Prior malignancy or treatment for malignancy within 5 years prior to randomization (except cured cutaneous basal cell carcinoma or cervical carcinoma in situ);

7. Subjects who have a previous history of psychiatric disorders (except for patients with current psychiatric disorders who are stable and not under medication control as judged by the investigator), or a history of drug or alcohol abuse within 12 months prior to Screening.

   General/Laboratory Tests

8. Abnormal liver function at screening: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 1.5 × ULN and/or total bilirubin (TBIL) ≥ 1.5 × ULN;
9. Abnormal renal function at screening: serum creatinine (Cr) ≥ 1.2 × ULN/blood urea nitrogen (BU)/blood urea nitrogen (BUN) ≥ 1.2 × ULN; Other conditions
10. Patients unable to undergo esophagogastroduodenoscopy (EGD);
11. Patients who are allergic to Annarazole Sodium or Rabeprazole Sodium and other drug ingredients or components that may be used in the study;
12. Use of therapeutic doses of drugs for gastroesophageal reflux disease such as proton pump inhibitors, potassium-competitive acid blockers, histamine H2 receptor antagonists, mucosal protective drugs, prokinetic drugs, anti-Helicobacter pylori drugs, and Chinese patent medicines for gastroesophageal reflux disease within 7 days before randomization;
13. Subjects who may affect the efficacy and safety evaluation due to alcohol, drug and drug withdrawal during the study;
14. Pregnant or lactating women, subjects with fertility plan from 30 days before randomization to half a year after the end of the trial;
15. Participation in another drug clinical trial (defined as receiving investigational product or placebo) within 3 months prior to randomization;
16. Other conditions that the investigator considers the subject unsuitable for this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anaprazole sodium 40 mg QD	Drug: Anaprazole sodium 40 mg; Anaprazole sodium 2 tablets (20 mg/tablet) + Anaprazole sodium dummy tablets 1 tablet (20 mg/tablet) + Rabeprazole sodium dummy tablets 2 tablets (10 mg/tablet) orally once daily within 30-60 minutes before breakfast for 8 weeks (after 4 weeks of continuous treatment, if endoscopy shows reflux esophagitis is cured, treatment is discontinued, into the safety follow-up period).
Experimental: Anaprazole sodium 60 mg QD	Drug: Anaprazole sodium 60 mg; Anaprazole sodium 3 tablets (20 mg/tablet) + Rabeprazole sodium dummy tablets 2 tablets (10 mg/tablet) orally once daily within 30-60 minutes before breakfast for 8 weeks (after 4 weeks of continuous treatment, if endoscopy shows reflux esophagitis is cured, treatment is discontinued, into the safety follow-up period).
Active Comparator: Rabeprazole sodium 20 mg QD	Drug: Rabeprazole sodium 20 mg; Anaprazole sodium dummy tablets 3 tablets (20 mg/tablet) + Rabeprazole sodium 2 tablets (10 mg/tablet) orally once daily within 30-60 minutes before breakfast for 8 weeks (after 4 weeks of continuous treatment, if endoscopy shows reflux esophagitis is cured, treatment is discontinued, into the safety follow-up period).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The endoscopic healing rate of reflux esophagitis within 8 weeks (including 8 weeks)	The endoscopic ulcer healing rate is defined as the percentage of patients with reflux esophagitis healed evaluated by blinded independency central reading. Reflux esophagitis is evaluated by endoscopy as per LA Classification.	Treatment of 4 weeks or 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of improvement in each individual symptom (daytime reflux)	The assessment of improvement of daytime reflux is evaluated in terms of severity and frequency. Mean severity scores are calculated for the first 7 days of the 4-week and 8-week visits, respectively. Mean score = sum of individual scores recorded over 7 days/number of days recorded. Complete response: mean score/score reduced to 0. Improvement:mean score/score reduced to 1. Ineffective: no change or increase in mean score/score. Complete response rate = number of complete response cases/total number of cases × 100%. Improvement rate = number of improved cases/total number of cases × 100%.	Treatment of 4 weeks or 8 weeks
The rate of improvement in each individual symptom (daytime heartburn)	The assessment of improvement of daytime heartburn is evaluated in terms of severity and frequency. Mean severity scores are calculated for the first 7 days of the 4-week and 8-week visits, respectively. Mean score = sum of individual scores recorded over 7 days/number of days recorded. Complete response: mean score/score reduced to 0. Improvement:mean score/score reduced to 1. Ineffective: no change or increase in mean score/score. Complete response rate = number of complete response cases/total number of cases × 100%. Improvement rate = number of improved cases/total number of cases × 100%.	Treatment of 4 weeks or 8 weeks
The rate of improvement in each individual symptom (nighttime reflux)	The assessment of improvement of nighttime reflux is evaluated in terms of severity and frequency. Mean severity scores are calculated for the first 7 days of the 4-week and 8-week visits, respectively. Mean score = sum of individual scores recorded over 7 days/number of days recorded. Complete response: mean score/score reduced to 0. Improvement:mean score/score reduced to 1. Ineffective: no change or increase in mean score/score. Complete response rate = number of complete response cases/total number of cases × 100%. Improvement rate = number of improved cases/total number of cases × 100%.	Treatment of 4 weeks or 8 weeks
The rate of improvement in each individual symptom (nighttime heartburn)	The assessment of improvement of nighttime heartburn is evaluated in terms of severity and frequency of each of the four individual symptoms. Mean severity scores are calculated for the first 7 days of the 4-week and 8-week visits, respectively. Mean score = sum of individual scores recorded over 7 days/number of days recorded. Complete response: mean score/score reduced to 0. Improvement:mean score/score reduced to 1. Ineffective: no change or increase in mean score/score. Complete response rate = number of complete response cases/total number of cases × 100%. Improvement rate = number of improved cases/total number of cases × 100%.	Treatment of 4 weeks or 8 weeks
Change From Baseline in gastroesophageal reflux disease health-related quality of life scale (GERD-HRQL) score	GERD related quality of life (QoL) is assessed with the "gastroesophageal reflux disease - health related quality of life" (GERD-HRQL) questionnaire. QoL is measured at baseline and at six months after treatment. The scale contains 10 questions and a symptom control satisfaction survey, which focuses on heartburn, acid reflux, swallowing function, and drug efficacy. Each question is scored according to a scoring criteria of 6 scores (0 indicates no symptoms, 5 indicates intolerable symptoms, and affects daily activities), and the total score is the sum of the scores of each item (0-50 points in total), with higher scores indicating worse quality of life. Satisfaction is divided into three levels: dissatisfaction, moderate, and satisfaction. Change in GERD-HRQL score = total GERD-HRQL score after treatment - total GERD-HRQL score before treatment.	Treatment of 4 weeks or 8 weeks
Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Enzyme Inhibitors; Proton Pump Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents
• Additional Relevant MeSH Terms: Pathologic Processes; Stomach Diseases; Gastroenteritis; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Disease; Gastroesophageal Reflux; Esophagitis, Peptic; Deglutition Disorders; Gastrointestinal Diseases; Digestive System Diseases; Esophagitis; Esophageal Diseases; Esophageal Motility Disorders; Esophageal Spasm, Diffuse; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: 3571-RE-2001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No