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

Purpose

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.

Condition	Intervention	Phase
Reflux Esophagitis	Drug: Esomeprazole 40mg Drug: YH4808 A mg Drug: YH4808 B mg Drug: YH4808 C mg	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: GERD

Drug Information available for: Omeprazole Omeprazole magnesium Esomeprazole Esomeprazole Sodium Esomeprazole magnesium

U.S. FDA Resources

Further study details as provided by Yuhan Corporation:

Primary Outcome Measures:

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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
Nocturnal Symptom Free Days & Symptom Free Days [ Time Frame: Treatment Period ] [ Designated as safety issue: No ]
Sustained resolution of symptom & Time to first sustained symptom resolution [ Time Frame: Treatment Period ] [ Designated as safety issue: No ]
Symptom Score [ Time Frame: Treatment Period ] [ Designated as safety issue: No ]
Serum Gastrin Level [ Time Frame: Check at Baseline(Pre-dose), 2, 4, and 8 weeks. ] [ Designated as safety issue: No ]
Global Impression of Change (Patient, Investigator) [ Time Frame: Check at 4, and 8 weeks. ] [ Designated as safety issue: No ]
Quality of Life [ Time Frame: Check at Baseline(Pre-dose), 4, and 8 weeks. ] [ Designated as safety issue: No ]
Epworth Sleepiness Scale [ Time Frame: Check at Baseline(Pre-dose), 2, 4, and 8 weeks. ] [ Designated as safety issue: No ]

Other Outcome Measures:

Nocturnal Symptom Free Days & Symptom Free Days [ Time Frame: Follow-up period ] [ Designated as safety issue: No ]
Sustained resolution of symptom [ Time Frame: Follow-up period ] [ Designated as safety issue: No ]
Symptom Score [ Time Frame: Follow-up period ] [ Designated as safety issue: No ]
Healing Rate of Reflux Esophagitis by Baseline According to Los Angeles Classification(LA Grade A~D Subgroup Analysis) [ Time Frame: Check at Baseline, Week 4 and Week 8 ] [ Designated as safety issue: No ]
Healing Rate of Reflux Esophagitis and Symptom related endpoints by H.pylori positive or negative [ Time Frame: Treatement & Follow-up period ] [ Designated as safety issue: No ]
Adverse events, Physical examination results, ECG, Vital sign, Lab results [ Time Frame: Treatment & Follow-up period ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	December 2012
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: YH4808 A mg (Twice daily) YH4808 A mg (Twice daily, Oral administration)	Drug: YH4808 A mg 1 tablet = YH4808 A mg Other Name: Undecided
Experimental: YH4808 B mg (Once daily) YH4808 B mg (Once daily, Oral administration)	Drug: YH4808 B mg 1 tablet = YH4808 B mg Other Name: Undecided
Experimental: YH4808 B mg (Twice daily) YH4808 B mg (Twice daily, Oral administration)	Drug: YH4808 B mg 1 tablet = YH4808 B mg Other Name: 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 Name: Undecided
Active Comparator: Esomeprazole 40mg (Once daily) Esomeprazole 40mg (Once daily, Oral administration)	Drug: Esomeprazole 40mg 1 tablet = Esomeprazole 40 mg Other Name: Nexium

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

Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01538849

Contacts

Contact: Seung Oh Lee	+82-2-828-0433	andrew90@yuhan.co.kr
Contact: Su Youn Nam, M.D., Ph.D.	+82-2-828-0432	namsu@yuhan.co.kr

Locations

Korea, Republic of
Seoul ST.MARY'S HOSPITAL	Recruiting
Seoul, Korea, Republic of, 137-701
Contact: Myung Gyu Choi, M.D., Ph.D. +82-2-2258-2083 choim@catholic.ac.kr

Sponsors and Collaborators

Yuhan Corporation

Investigators

Principal Investigator:

Myung Gyy Choi, M.D., Ph.D.

Catholic Univ. Seoul St. Mary Hospital

More Information

No publications provided

Responsible Party:	Yuhan Corporation
ClinicalTrials.gov Identifier:	NCT01538849 History of Changes
Other Study ID Numbers:	YH4808-201
Study First Received:	February 20, 2012
Last Updated:	May 13, 2013
Health Authority:	Korea: Ministry of Food and Drug Safety

Additional relevant MeSH terms:

Esophagitis
Esophagitis, Peptic
Gastroesophageal Reflux
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Peptic Ulcer
Esophageal Motility Disorders

Deglutition Disorders
Omeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013