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

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

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.

Study Overview

• Status: Completed
• Conditions: Reflux Esophagitis
• Intervention / Treatment: Drug: YH4808 A mg; Drug: YH4808 B mg; Drug: YH4808 C mg; Drug: Esomeprazole 40mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
    • Seoul St.Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject who has signed on the written consent
2. Male and female aged 20 and over
3. Endoscopically verified Reflux Esophagitis classified into Los Angeles classification Grade A, B, C or D within 2 weeks before randomisation

Exclusion Criteria:

1. History or presence of upper gastrointestinal anatomic or motor disorders
2. Other exclusions apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Other Outcome Measures

Outcome Measure	Time Frame
Nocturnal Symptom Free Days & Symptom Free Days	Follow-up period
Sustained resolution of symptom	Follow-up period
Symptom Score	Follow-up period
Healing Rate of Reflux Esophagitis by Baseline According to Los Angeles Classification(LA Grade A~D Subgroup Analysis)	Check at Baseline, Week 4 and Week 8
Healing Rate of Reflux Esophagitis and Symptom related endpoints by H.pylori positive or negative	Treatement & Follow-up period
Adverse events, Physical examination results, ECG, Vital sign, Lab results	Treatment & Follow-up period

Collaborators and Investigators

• Sponsor: Yuhan Corporation
• Investigators: Principal Investigator: Myung Gyy Choi, M.D., Ph.D., Catholic Univ. Seoul St. Mary Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: February 20, 2012
• First Submitted That Met QC Criteria: February 23, 2012
• First Posted (Estimate): February 24, 2012

Study Record Updates

• Last Update Posted (Estimate): July 10, 2014
• Last Update Submitted That Met QC Criteria: July 8, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: YH4808-201