Study to Investigate the Safety, Tolerability and Efficacy of YH4808 in Patients With Reflux Esophagitis

Study Overview
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Brief Summary
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This study is to investigate the optimal clinical dose and administration methods of YH4808 in patients with reflux esophagitis by evaluating the safety and efficacy after YH4808 oral administration.

Detailed Description
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In the result of recent meta-analysis, there was no improvement in symptoms with the first administration of PPI in about 75% of GERD patients, and symptoms were still sustained in about 50% of patients after administration of more than 3 days. Especially the nocturnal secretion of gastric acid was not effectively inhibited, and about 25% of GERD patients could not achieve the proper therapeutic effects even after PPI treatment twice daily for 4-8 weeks. YH4808, as a selective K+- competitive acid blocker (P-CAB), is no need for activation by gastric acid since it competitively inhibits proton pump with K+. Thus, the inhibition of gastric acid secretion by YH4808 is prompt and effective. In addition, the inhibitive effect of gastric acid secretion by stimulation of histamine is proved to be more powerful than PPI (esomeprazole) and sustained in in-vitro/in-vivo model, and 24-h inhibition of gastric acid secretion and especially nocturnal inhibition of gastric acid secretion was observed to be superior to esomeprazole with repeat doses for 7 days in healthy volunteers. Based on these nonclinical and clinical outcomes, an exploratory phase-II clinical trial is to be conducted to determine the proper treatment dose and administration method of YH48084 for GERD patients.

Official Title
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Randomized, Double-blind, Active-controlled, Multi-center Clinical Trial to Investigate the Safety, Tolerability and Efficacy of YH4808 in Patients With Reflux Esophagitis

Conditions
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Reflux Esophagitis

Intervention / Treatment
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* Drug: Esomeprazole 40mg
* Drug: YH4808 A mg
* Drug: YH4808 B mg
* Drug: YH4808 C mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who has signed on the written consent Male and female aged 20 and over Endoscopically verified Reflux Esophagitis classified into Los Angeles classification Grade A, B, C or D within 2 weeks before randomisation Exclusion Criteria: History or presence of upper gastrointestinal anatomic or motor disorders Other exclusions apply.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YH4808 A mg (Twice daily)<br>YH4808 A mg (Twice daily, Oral administration) | Drug: YH4808 A mg<br>* 1 tablet = YH4808 A mg<br>* Other names: Undecided;|
| Experimental: YH4808 B mg (Once daily)<br>YH4808 B mg (Once daily, Oral administration) | Drug: YH4808 B mg<br>* 1 tablet = YH4808 B mg<br>* Other names: Undecided;|
| Experimental: YH4808 B mg (Twice daily)<br>YH4808 B mg (Twice daily, Oral administration) | Drug: YH4808 B mg<br>* 1 tablet = YH4808 B mg<br>* Other names: Undecided;|
| Experimental: YH4808 C mg (Once daily)<br>YH4808 C mg (Once daily, Oral administration) | Drug: YH4808 C mg<br>* YH4808 C mg = 2 x YH4808 B mg<br>* Other names: Undecided;|
| Active Comparator: Esomeprazole 40mg (Once daily)<br>Esomeprazole 40mg (Once daily, Oral administration) | Drug: Esomeprazole 40mg<br>* 1 tablet = Esomeprazole 40 mg<br>* Other names: Nexium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Healing of Reflux Esophagitis (RE) Who Were Normal(including minimal change) at Week 4 Out of Patients Who Were Graded A, B, C or D at Baseline According to Los Angeles Classification |  | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Healing of Reflux Esophagitis (RE) Who Were Normal(including minimal change) at Week 8 Out of Patients Who Were Graded A, B, C or D at Baseline According to Los Angeles Classification |  | Week 8 | 
| Nocturnal Symptom Free Days & Symptom Free Days |  | Treatment Period | 
| Sustained resolution of symptom & Time to first sustained symptom resolution |  | Treatment Period | 
| Symptom Score |  | Treatment Period | 
| Serum Gastrin Level |  | Check at Baseline(Pre-dose), 2, 4, and 8 weeks. | 
| Global Impression of Change (Patient, Investigator) |  | Check at 4, and 8 weeks. | 
| Quality of Life |  | Check at Baseline(Pre-dose), 4, and 8 weeks. | 
| Epworth Sleepiness Scale |  | Check at Baseline(Pre-dose), 2, 4, and 8 weeks. |