초록 ▼

1) 임상연구
: 비변비형 환자를 대상으로 SKI3246의 위약 대비 약효 및 안전성을 확인하는 임상연구를 완료하였으나, 일차, 이차 유효성 평가 변수에서 위약 대비 통계학적으로 유의미한 결과를 확보하지 못함
: 추가적으로 다양한 임상결과 분석을 통해 FDA 가이드라인 (2012년 3월)에 따라 복부통증 VAS 기준 51-100을 갖는 pain intensity responder를 subgroup 분석해 본 결과, SKI3246 300mg이 위약 대비 pain intensity responder와 overall respo

1) 임상연구
: 비변비형 환자를 대상으로 SKI3246의 위약 대비 약효 및 안전성을 확인하는 임상연구를 완료하였으나, 일차, 이차 유효성 평가 변수에서 위약 대비 통계학적으로 유의미한 결과를 확보하지 못함
: 추가적으로 다양한 임상결과 분석을 통해 FDA 가이드라인 (2012년 3월)에 따라 복부통증 VAS 기준 51-100을 갖는 pain intensity responder를 subgroup 분석해 본 결과, SKI3246 300mg이 위약 대비 pain intensity responder와 overall responder가 통계적으로 유의함을 확인할 수 있었음
2) 비임상 독성 연구
: 랫드에서의 26주반복투여 독성시험에서 SKI3246의 무해용량 (NOAEL)은 암수 모두 2000 mg/kg/day 이상
3) value up 연구
: 규격화, 표준화의 일환으로 표준품 약 12g을 제조 및 documentation
: 표준품 및 원료, 완제에 대한 장기 안정성 연구 (최대 3년)도 진행
: NKA (Neurokinin A)에 의해 증가된 랫드의 상부위장관 운동에 대한 SKI3246의 억제효과를 확인

Abstract ▼

1. Background of the Study
IBS is a functional bowel disorder, characterized by multiple symptoms, such as abdominal pain, discomfort, diarrhea, and/or constipation. Over the past few decades, a wide range of therapeutic targets have been proposed to treat IBS.However, there are still unmet needs

1. Background of the Study
IBS is a functional bowel disorder, characterized by multiple symptoms, such as abdominal pain, discomfort, diarrhea, and/or constipation. Over the past few decades, a wide range of therapeutic targets have been proposed to treat IBS.However, there are still unmet needs for novel therapeutic agents, which are safer and more effective than conventional drugs.
SKI3246 is the standardized herbal extract from Atractylodes japonica rhizome, used as a traditional herbal medicine in the treatment of digestive disorders. In previous studies, we have found SKI3246 could reduce the abdominal pain caused by visceral hypersensitivity and improve abnormal bowel movements induced by stress without adverse effects such as constipation, contrary to other conventional 5-HT3 antagonists.

Ⅱ. Content and Range of the Study
1) Clinical study
: The purpose of this study is to determine the efficacy and safety of SKI3246 (300mg or 600mg, twice daily) compared with placebo in the treatment of non-constipation IBS patients. As primary outcome measures, global assessment of relief on the 12th week of treatment (visit 5) was measured by the SGA (subject global assessment) of relief-5 point likert scale
2) Non-clinical toxicity study
: The objective of this study is to investigate the toxicity of SKI3246 (26-week treatment and 13-week recovery period, SD rat).
3) Value-up study
: The aim of this study is to identify key differentiators and to gain competitive advantage. Standardization and additional pharmacological studies were carried out.

Ⅲ. Results of the study
1) Clinical study
: A total of 307 subjects have been enrolled. Out of them, 253 have completed the study in compliance with the protocol.
: Considering both primary and secondary outcome measures, the results of study were not statistically meaningful in comparison with placebo. However, the subgroup analysis of pain intensity responders based on the FDA guidance (Mar. 2012) with the subjects whose abdominal pain VAS score is 51 - 100 showed the statistically significant difference between two groups (SKI3246 300mg and placebo) in terms of pain intensity responder and overall responder.
2) Non-clinical toxicity study
: The NOAEL of SKI3246 is considered to be 2000 mg/kg/day or more in both sexes in this study.
3) Value-up study
: We established standard documentation and tested the long-term stability of drug substances, products and reference standars (up to 3 years). We also found SKI3246 can inhibit increased upper GI transit by NKA in SD rats.