[Translation] A randomized, open-label, two-period, two-crossover single-dose bioequivalence study of bicyclol tablets (25 mg) in healthy subjects under fasting/fed conditions

主要目的：在健康男性与女性受试者中于空腹/餐后条件下，评价受试制剂双环醇片（规格：25 mg，生产商：浙江华海药业股份有限公司）和北京协和药厂有限公司生产的参比制剂双环醇片（百赛诺，规格：25 mg）的生物等效性。次要目的：观察受试制剂双环醇片与参比制剂双环醇片（百赛诺）在健康受试者中的安全性。

[Translation]

Primary objective: To evaluate the bioequivalence of the test preparation Bicyclol Tablets (Specification: 25 mg, Manufacturer: Zhejiang Huahai Pharmaceutical Co., Ltd.) and the reference preparation Bicyclol Tablets (Bisano, Specification: 25 mg) produced by Beijing Union Pharmaceutical Co., Ltd. in healthy male and female subjects under fasting/postprandial conditions. Secondary objective: To observe the safety of the test preparation Bicyclol Tablets and the reference preparation Bicyclol Tablets (Bisano) in healthy subjects.

Start Date03 Mar 2024

Sponsor / Collaborator

Zhejiang Huahai Pharmaceutical Co., Ltd.

CTR20231453 / RecruitingPhase 4

双环醇片治疗急性药物性肝损伤多中心、随机、双盲、阳性对照Ⅲ期临床试验——延伸性长期观察研究

[Translation] A multicenter, randomized, double-blind, positive-controlled phase III clinical trial of bicyclol tablets in the treatment of acute drug-induced liver injury: an extended long-term observation study

对完成双环醇片治疗急性药物性肝损伤多中心、随机、双盲、阳性对照Ⅲ期临床试验的受试者进行延伸性长期观察研究，考察肝损伤的远期预后。

[Translation]

An extended long-term observation study was conducted on subjects who completed the multicenter, randomized, double-blind, positive-controlled Phase III clinical trial of bicyclol tablets in the treatment of acute drug-induced liver injury to examine the long-term prognosis of liver injury.

Start Date15 Aug 2023

Sponsor / Collaborator

Beijing Union Pharmaceutical Factory

NCT05711459 / RecruitingNot ApplicableIIT

A Prospective and Multicenter Cohort Study of Bicyclol in the Treatment of Antineoplastic Drug-induced Liver Injury.

The clinical trial is designed to evaluate the efficacy of bicyclol for patients with antineoplastic drug-induced liver injury and investigate factors effecting the therapeutic outcome.

Start Date01 May 2022

Sponsor / Collaborator

Tianjin Cancer Institute

100 Clinical Results associated with Bicyclol

100 Translational Medicine associated with Bicyclol

100 Patents (Medical) associated with Bicyclol

175

Literatures (Medical) associated with Bicyclol

12 Nov 2024·Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases

[Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)].

Review

Drug-induced liver injury (DILI) is one of the most common adverse reactions of anti-tuberculosis treatment. To improve the diagnosis and management of anti-tuberculosis drug-induced liver injury (ATB-DILI) for clinicians and tuberculosis control workers, the Chinese Medical Association Tuberculosis Branch has developed guidelines for the diagnosis and treatment of ATB-DILI. These guidelines summarized recent research progress in relevant fields and provide detailed explanations, recommendations, and quality assessments related to ATB-DILI, covering aspects such as definition, risk factors, mechanisms, pathological manifestations, clinical classification, diagnosis, and management. The key recommendations are as follows.Recommendation 1: Risk factors: NAT2 slow acetylation genotype, GSTM1 gene variation, advanced age, hepatitis virus infection or concurrent acute/chronic liver disease, HIV infection, malnutrition, and alcohol (ethanol) intake are risk factors for ATB-DILI (2, B).Recommendation 2: R-value calculation: Calculate the R-value for suspected ATB-DILI patients at different time points during the course of the disease. ALT and ALP values should be obtained on the same day, with a maximum interval of no more than 48 hours. This helps to accurately determine the clinical type and prognosis of DILI (2, C).Recommendation 3: Comprehensive medical history collection: Collect information on past medication history, clinical features, dynamic changes in liver biochemical markers, drug rechallenge reactions, comorbidities, and underlying liver diseases (4, B).Recommendation 4: Liver biochemical tests: Include at least ALT, AST, ALP, GGT, TBil, DBil, and albumin. If necessary, measure prothrombin time or international normalized ratio (INR) (3, B).Recommendation 5: Abdominal imaging: Routine abdominal imaging should be performed for suspected ATB-DILI patients (3, B).Recommendation 6: Liver histopathological examination: Histology of liver biopsies aids in the diagnosis and differential diagnosis of DILI (4, B).Recommendation 7: Biochemical diagnostic criteria for acute ATB-DILI: Liver biochemical tests should meet one of the following criteria: ALT≥3×ULN and/or TBil≥2×ULN; simultaneous elevation of AST, ALP, and TBil, with at least one parameter≥2×ULN (4, C).Recommendation 8: Diagnostic criteria for ATB-DILI: Diagnosis requires:(1) A history of exposure to anti-tuberculosis drugs that can cause liver injury;(2)Rapid normalization of abnormal liver biochemical markers after drug discontinuation: For patients with hepatocellular injury, a decrease in the peak serum ALT level of at least 50% within 8 days is highly suggestive, while a decrease of at least 50% within 30 days is considered important. For patients with cholestatic injury, a serum ALP or TBil peak level that decreases by at least 50% within 180 days is also considered important;(3) Exclusion of other causes of liver injury;(4) Positive rechallenge reaction. Meeting three of the above criteria confirms ATB-DILI, whereas meeting (1) and (2) criteria indicates a suspected case. In practice, the vast majority of ATB-DILI are suspected cases (3, B).Recommendation 9: Avoid re-exposure: Minimize re-exposure to the same suspected drug, especially if the initial exposure caused severe liver injury (4, B).Recommendation 10: Causality assessment: Use the RUCAM scale as the primary method for assessing causality. In cases involving multiple hepatotoxic drugs, concurrent liver disease, or new drug clinical trials, combine expert opinions for reliable assessment (3, B).Recommendation 11: Baseline testing: All patients are recommended to undergo baseline liver biochemistry, HBsAg (if HBsAg is positive, further HBV DNA testing), anti-HCV testing, and abdominal imaging before starting anti-TB treatment (3, B).Recommendation 12: Monitoring frequency: Patients without high-risk factors should have monthly liver biochemical monitoring (4, C);high-risk patients or those using hepatotoxic drugs should be monitored every 2 weeks during the first 2 months of anti-tuberculosis treatment, then monthly (2, B).Recommendation 13: Avoid concurrent hepatotoxic drugs: Evaluate the benefit-risk ratio of using other hepatotoxic drugs or traditional Chinese medicine (4, C).Recommendation 14: Antiviral treatment: In ATB-DILI patients with viral hepatitis, consider prompt antiviral therapy if indicated (3, B).Recommendation 15: NAT2 genotyping: Guide isoniazid dosing based on NAT2 gene polymorphism (4, C).Recommendation 16: Application of preventive hepatoprotective drugs: People with high risk factors for liver damage may consider it (4, C); however, routine use in the general population is not recommended (2, B).Recommendation 17: Immediate discontinuation: In the case of ATB-DILI, suspected drugs should be discontinued immediately (4, A).Recommendation 18: N-acetylcysteine (NAC): Early intravenous administration of NAC is beneficial for acute liver failure and subacute liver failure induced by drugs in adults (4, D).Recommendation 19: Glucocorticoids: Use with caution;not recommended as routine treatment for ATB-DILI(4, C);may be considered for immune-mediated DILI with hypersensitivity and autoimmune features (3, B).Recommendation 20: For acute hepatocellular injury or mixed DILI with significantly elevated ALT/AST, bicyclol and/or magnesium isoglycyrrhizinate are recommended (2, B).Recommendation 21: For mild to moderate hepatocellular injury type DILI with elevated ALT/AST, reasonable choices include ammonium glycyrrhizinate, compound glycyrrhizin, and other glycyrrhizic acid derivatives, glutathione, silymarin, polyenylphosphatidylcholine, and other drugs (4, C); For cholestatic DILI with elevated ALP/GGT/TBil, ursodeoxycholic acid or S-adenosylmethionine may be selected (4, C); the combined use of two or more drugs that mainly reduce ALT is not recommended (4, B).Recommendation 22: Treatment of severe patients: For severe patients such as those with drug-induced liver failure, liver transplantation is recommended (2, B); artificial liver (high-volume plasma exchange, dual plasma molecular adsorption system, etc.) may be a beneficial option (4, C); ornithine aspartate may help reduce blood ammonia levels in patients with severe disease or liver failure (4, C).Recommendation 23: Rational drug use during the recovery period: During or after liver function recovery, clinicians should comprehensively assess the patient's liver injury severity, presence of liver injury-related risk factors, and tuberculosis severity. Based on this assessment, anti-tuberculosis drugs should be selected rationally (4, C). These recommendations provide clinical evidence and decision-making guidance for the standardized diagnosis and treatment of ATB-DILI.

02 Aug 2024·Journal of Asian Natural Products Research

Characterization of the metabolic contributions of cytochrome P450 isoforms to bicyclol using the relative activity factor method

Article

Author: Sheng, Li ; Luo, Li-jun ; Li, Yang ; Liu, Xiao ; Li, Yan

Bicyclol is a hepatoprotective agent widely used for treating chronic hepatitis and drug-induced liver injuries in clinics. The purpose of the study was to elucidate the contribution of CYP450 enzymes to the metabolism of bicyclol using the relative activity factor approach. After incubation with human liver microsomes and recombinant human liver CYP450 enzymes, the calculated contribution of CYP3A4 and 2C19 to the metabolism of bicyclol was 85.6-90.3% and 9.2-9.7%, respectively. The metabolism was interrupted in the presence of CYP3A4 and 2C19 selective inhibitors. These findings help to predict or avoid metabolic drug-drug interactions or toxicity in clinical applications of bicyclol.

01 Jun 2024·Cardiovascular Drugs and Therapy

Bicyclol Alleviates Streptozotocin-induced Diabetic Cardiomyopathy By Inhibiting Chronic Inflammation And Oxidative Stress

Article

Author: Wang, Minxiu ; Bai, Bin ; Wu, Xuedan ; Jin, Leiming ; Zheng, Li ; Zhang, Lingxi ; Wang, Yi ; Jiang, Yongsheng ; Hu, Chenghong ; Zhu, Weiwei ; Xu, Xuelian ; Liao, Jing ; He, Ying ; Jin, Bo

PURPOSEDiabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM.METHODSA type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells.RESULTSWe showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects.CONCLUSIONOur data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.

100 Deals associated with Bicyclol

External Link

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Fatty Liver	CN	-	18 Oct 2001
Hepatitis, Viral, Human	UA	-	11 Oct 2001
Hepatitis B	CN	Beijing Union Pharmaceutical Factory	01 Jan 2001

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chemical and Drug Induced Liver Injury	Phase 3	CN	Beijing Union Pharmaceutical Factory	13 Dec 2021
Hepatitis, Chronic	Phase 1	CN	Beijing Union Pharmaceutical Factory	15 May 2015
Liver Cancer	Phase 1	CN	Chinese Academy of Medical Sciences	-

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02944552 (Pubmed \| Liver Int)	Phase 2	Chemical and Drug Induced Liver Injury	241	Low-dose bicyclol (25 mg TID)	cqxyfuoqoh(xickjjwgzf) = fiyqsofowm hmydpzzlfo (xfldgkbodx )	Positive	14 May 2022
				High-dose bicyclol (50 mg TID)	cqxyfuoqoh(xickjjwgzf) = eingaqulxl hmydpzzlfo (xfldgkbodx )

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