The Korean Journal of Medicine

  • 제86권2호
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  • Pages.179-189
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  • 2014
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  • 1738-9364(pISSN)
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  • 2289-0769(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
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DOI QR코드

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만성 간질환에서 펜넬$^{(R)}$의 무작위, 이중맹검, 다기관 제4상 임상시험

The PERFECT Study (PEnnel Real liFe Efficacy Clinical Trial), a Double-Blind, Randomized, Multicenter Trial Examining the Efficacy of Biphenyl Dimethyl Dicarboxylate Combined with Garlic Oil in Patients with Transaminase Elevated Chronic Liver Disease

  • 김형준 (중앙대학교 의과대학 내과학교실) ;
  • 이준성 (인제대학교 의과대학 내과학교실) ;
  • 이현웅 (중앙대학교 의과대학 내과학교실) ;
  • 김문영 (연세대학교 원주의과대학 내과학교실) ;
  • 남순우 (가톨릭대학교 의과대학 내과학교실) ;
  • 손주현 (한양대학교 의과대학 내과학교실) ;
  • 조세현 (가톨릭대학교 의과대학 내과학교실) ;
  • 윤승규 (가톨릭대학교 의과대학 내과학교실) ;
  • 양진모 (가톨릭대학교 의과대학 내과학교실) ;
  • 박충기 (한림대학교 의과대학 내과학교실) ;
  • 임규성 (차의과대학교 내과학교실) ;
  • 이영석 (가톨릭대학교 의과대학 내과학교실)
  • Kim, Hyung Joon (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Lee, June Sung (Department of Internal Medicine, Inje University College of Medicine) ;
  • Lee, Hyun Woong (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Kim, Mun Young (Department of Internal Medicine, Yonsei University Wonju College of Medicine) ;
  • Nam, Soon Woo (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Sohn, Ju Hyun (Department of Internal Medicine, Hanyang University College of Medicine) ;
  • Cho, Se Hyun (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Yoon, Seung Gyu (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Yang, Jin Mo (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Park, Chung Kee (Department of Internal Medicine, Hallym University College of Medicine) ;
  • Rim, Gyu Sung (Department of Internal Medicine, CHA University) ;
  • Lee, Young Sok (Department of Internal Medicine, The Catholic University of Korea College of Medicine)
  • 투고 : 2013.10.02
  • 심사 : 2013.11.21
  • 발행 : 2014.02.01
⟨ 이전 논문 다음 논문 ⟩

초록

목적: 펜넬(Pennel$^{(R)}$)은 DDB에 마늘유(garlic oil)를 복합시킨 제제로 혈청 트랜스아미나제(AST와/또는 ALT)가 상승된 만성 간 질환자에서 펜넬의 치료 효과에 대한 유효성을 검증하기 위해 활성대조약인 레가론, 위약군과 비교 평가한 다기관 제 4상 임상연구를 실시하였다. 방법: 총 11개 병원, 237명의 피험자가 연구에 참여하였다. 이 중 시험약군은 100명, 활성대조군은 102명, 위약군은 35명이었다. 12주간의 치료기간 동안 순응도는 좋았으며 중도 탈락은 없었다. 환자의 연령은 평균 46세, 남성의 비율이 높았다. 치료 전 ALT 값은 91 U/L였으며 66%가 비알코올성 지방간염, 15%가 알코올성 간염, 12%가 만성 C형간염 그리고 7%가 만성 B형간염 환자였다. 결과: 약물 투약 12주째 ALT 정상화 분율은 시험약군이 89명으로 89%, 활성대조군이 19명으로 18.6%, 위약군이 8명으로 22.9%로 나타났다(p < 0.001). 간염의 원인에 따른 분류에서도 시험군에서 통계적으로 의미 있게 ALT 정상화 분율의 비율이 높았다. 치료 전 대비 치료 12주의 ALT는 시험약군에서 평균 85 U/L 감소하였으나 활성대조군은 20 U/L, 위약군은 25 U/L 감소하였다. 항산화 효과 지표인 malondialdehyde (MDA)는 시험약군에서만 1.4 pmol/mg의 호전을 보였다. 하위그룹분석에서 비알코올성 지방간염과, 바이러스성 간염환자에서 의미 있게 MDA 수치의 호전을 보였다(p < 0.001). 시험약물의 안전성 평가에서도 이상반응의 발생빈도가 위약군에 비해 차이가 없었다. 이상반응의 대부분은 감기, 피로, 설사 및 소화불량 등 grade 1의 경증이었으며 중대한 이상반응은 없었다. 삶의 질 평가 총점수도 시험약군이 치료 12주에 10점 이상 통계적으로 의미 있게 증가하였다(p < 0.001). 결론: 결론적으로 ALT가 상승한 만성 간 질환자를 대상으로 한 12주간의 펜넬 4상 임상 시험의 유효성과 안전성 평가에서 펜넬은 원인 질환과 무관하게 치료 4주 만에 급격한 ALT 수치의 정상화를 유도하였으며 항산화 효과를 보였다. 치료기간 동안 부작용이 거의 없는 안전한 약제로서 순응도가 뛰어났으며, 치료 후 삶의 질이 의미 있게 개선되는 효과를 보였다.

Background/Aims: Biphenyl dimethyl dicarboxylate (DDB) combined with garlic oil (pennel) has been used to treat chronic liver disease. A randomized, double-blind, active- and placebo-controlled clinical trial was conducted to investigate the efficacy, safety and quality of life in chronic liver disease patients. Methods: A total of 237 patients with chronic liver disease were randomized into three groups; 100 patients were administered pennel, 102 patients Legalon as an active-control and 35 patients placebo for 12 weeks. The primary endpoint was the rate of alanine aminotransferase (ALT) normalization. We assessed differences in ALT levels and malondialdehyde (MDA) as an oxidative biomarker between 0 and 12 weeks, the improvement in quality of life using a chronic liver disease questionnaire (CLDQ) and the incidence of adverse events. Results: Among 237 patients, there were 157 patients with non-alcoholic fatty liver disease, 36 patients with alcoholic liver disease, and 28 patients with chronic hepatitis B and C. The incidence of ALT normalization at 12 weeks was 89% for the pennel group, 18.6% for the active-control group, and 22.9% for the placebo-control group (p < 0.001). The difference in serum ALT level between 0 and 12 weeks was significantly higher in the pennel group (p < 0.001) and the level of MDA was decreased in the pennel group, statistically (p < 0.001). There was no difference in incidence of adverse events among groups. The pennel group showed significant improvement based on the CLDQ (p < 0.001). Conclusions: Pennel can effectively improve the rate of ALT normalization and the quality of life with a safety profile in chronic liver disease.

키워드

과제정보

연구 과제 주관 기관 : PharmaKing Company

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  2. Efficacy and Safety of Biphenyl Dimethyl Dicarboxylate and Ursodeoxycholic Acid Combination in Chronic Hepatitis Related to Metabolic Syndrome Components vol.77, pp.4, 2014, https://doi.org/10.4166/kjg.2020.158