초록 ▼

가역적 위산펌프길항제인 YH4808 약물을 위식도역류질환 및 소화성궤양치료제로 개발하기 위해 건강한 성인남성을 대상으로한 단회 및 반복투여 제1상 임상시험 및 후기 임상개발을 위한 비임상 중장기독성시험, 공정개발 연구 및 약리학적 특장점 연구를 수행하였음.
1상 임상시험결과 YH4808은 단회 800mg까지 우수한 내약성을 나타내었으며, 100mg 이상의 용량에서 우수한 위내 pH 조절효능을 나타내었고, 독성시험에서도 특별한 독성이 관찰되지 않았기에, 식도염환자에 대한 제2상임상시험을 추진하고자 IND를 신청하여 승인을 획득하

가역적 위산펌프길항제인 YH4808 약물을 위식도역류질환 및 소화성궤양치료제로 개발하기 위해 건강한 성인남성을 대상으로한 단회 및 반복투여 제1상 임상시험 및 후기 임상개발을 위한 비임상 중장기독성시험, 공정개발 연구 및 약리학적 특장점 연구를 수행하였음.
1상 임상시험결과 YH4808은 단회 800mg까지 우수한 내약성을 나타내었으며, 100mg 이상의 용량에서 우수한 위내 pH 조절효능을 나타내었고, 독성시험에서도 특별한 독성이 관찰되지 않았기에, 식도염환자에 대한 제2상임상시험을 추진하고자 IND를 신청하여 승인을 획득하였음.

Abstract ▼

1. Objective: YH4808 is a reversible acid pump antagonist with new chemical entity. The objectives of this project was to perform first-in-human clinical study in healthy volunteers and non-clinical studies to develop YH4808 as new therapeutics for the gastroesophageal reflux disease (GERD) and pept

1. Objective: YH4808 is a reversible acid pump antagonist with new chemical entity. The objectives of this project was to perform first-in-human clinical study in healthy volunteers and non-clinical studies to develop YH4808 as new therapeutics for the gastroesophageal reflux disease (GERD) and peptic ulcer diseases.
2. The scope of the project: Scope of this project was 1) phase 1 clinical study in healthy male volunteers with single or multiple (7 days) ascending doses of YH4808, 2) non-clinical toxicity studies to support late stage development, 3) process development for the API, 4) non-clinical pharmacology studies to support differentiation points, and 5) filing of IND for phase 2 clinical study.
3. Results
1) Phase 1 clinical study: Healthy male subjects were received single (30mg, 50mg, 100mg, 200mg, 400mg, 600mg, 800mg) or 7 days multiple (100mg, 200mg, 400mg) ascending doses of YH4808 to investigate the safety and PK/PD. YH4808 was well tolerated up to highest dose with no severe adverse events and showed rapid onset of efficacy. Especially, YH4808 maintained time above gastric pH > 4 more than 16 hours at the doses above 200 mg and this results predict very high clinical efficacy in GERD patients.
2) Non-clinical toxicity: 26-week toxicity study in rats and 13-week toxicity study in monkeys were performed. Systemic exposure of YH4808 was increased as to the doses were increased.
There was no noticeable toxicity observed except the changes in stomach such as thickening of the stomach wall and chief cell hyperplasia which is believed to be related with pharmacological mechanism of YH4808 and was reversible.
3) Process development: By optimization of starting material and reducing the production steps for the API, the production cost of YH4808 was reduced approximately 70% compared with previous process.
4) Formulation development: Excipients for the new formulation which would have better PK and clinical efficacy were determined and drug product was stable up to 24 months after manufacturing.
4. Final achievement and plan
1) Based on the excellent clinical study outcome from Phase 1 study and favorable non-clinical studies, IND for Phase 2 study was filed and approved by the regulatory authority on Feb. 2012.
2) After completion of Phase 2 study, further clinical development and commercialization in Korea and licensing out to multinational pharma company will be pursued.

목차 Contents

• 표지 ... 1
• 제출문 ... 3
• 보고서 요약서 ... 4
• 요 약 문 ... 5
• SUMMARY ... 6
• 연구 성과 실적 및 향후 계획 ... 7
• 참여연구원 현황표 ... 14
• II. 총괄연구과제 연구결과 ... 15
• 1. 연구개발과제의 배경 및 필요성 ... 16
• 2. 국내외 기술개발 현황 ... 19
• 3. 연구개발과제의 추진체계 ... 21
• 4. 연구개발수행 내용 및 결과 ... 22
• 5. 목표달성도 및 관련분야 기여도 ... 34
• 6. 향후 연구성과 추진 계획 ... 36
• 7. 연구개발결과의 파급효과 ... 36
• 8. 연구개발결과의 활용계획 ... 39
• 9. 연구개발과정에서 수집한 해외과학기술정보 ... 40
• 10. 참고문헌 ... 40
• III. 첨부서류 ... 41
• 1. 자체평가의견서 ... 43
• 2. 실적 증빙자료 ... 47