Clinical trial NCT01538849: Study to Investigate the Safety, Tolerability and Efficacy of YH4808 in Patients With Reflux Esophagitis
Official title: Randomized, Double-blind, Active-controlled, Multi-center Clinical Trial to Investigate the Safety, Tolerability and Efficacy of YH4808 in Patients With Reflux Esophagitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Reflux Esophagitis
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2012-02-24
Enrollment: 154
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Week 4
Secondary outcomes:
measure: 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
timeFrame: Week 8
measure: Nocturnal Symptom Free Days & Symptom Free Days
timeFrame: Treatment Period
measure: Sustained resolution of symptom & Time to first sustained symptom resolution
timeFrame: Treatment Period
measure: Symptom Score
timeFrame: Treatment Period
measure: Serum Gastrin Level
timeFrame: Check at Baseline(Pre-dose), 2, 4, and 8 weeks.
measure: Global Impression of Change (Patient, Investigator)
timeFrame: Check at 4, and 8 weeks.
measure: Quality of Life
timeFrame: Check at Baseline(Pre-dose), 4, and 8 weeks.
measure: Epworth Sleepiness Scale
timeFrame: Check at Baseline(Pre-dose), 2, 4, and 8 weeks.
Other outcomes:
measure: Nocturnal Symptom Free Days & Symptom Free Days
timeFrame: Follow-up period
measure: Sustained resolution of symptom
timeFrame: Follow-up period
measure: Symptom Score
timeFrame: Follow-up period
measure: Healing Rate of Reflux Esophagitis by Baseline According to Los Angeles Classification(LA Grade A~D Subgroup Analysis)
timeFrame: Check at Baseline, Week 4 and Week 8
measure: Healing Rate of Reflux Esophagitis and Symptom related endpoints by H.pylori positive or negative
timeFrame: Treatement & Follow-up period
measure: Adverse events, Physical examination results, ECG, Vital sign, Lab results
timeFrame: Treatment & Follow-up period
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul ST.MARY'S HOSPITAL
Study officials:
affiliation: Catholic Univ. Seoul St. Mary Hospital
name: Myung Gyy Choi, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: