A Phase III, Randomized, Open Label, Active Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Ademetionine 1,4-Butane Disulfonate 500 mg Lyophilized Powder for Injection in Adult Patients with Intrahepatic Cholestasis (IHC).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 10
- 主要终点
- Mean change in serum total bilirubin and serum conjugated bilirubin from baseline to end of the study visit (week 2).
研究概览
简要总结
This trial is a phase III, randomized, open label, active controlled, prospective, parallel group, comparative, multicentric clinical study to evaluate the efficacy, safety and tolerability of Ademetionine 1,4-Butane Disulfonate 500 mg Lyophilized Powder for Injection in adult patients with intrahepatic cholestasis (IHC).
Patients who are willing and able to participate in the study will sign and date the Informed Consent Form on the day of screening or baseline visit (Visit 1). During this screening period, patients who are willing to give consent will be evaluated for all the eligibility criteria. Eligible patients (male and female) aged between 18 to 65 years (both inclusive), with a diagnosis of intrahepatic cholestasis (IHC) [Serum total bilirubin and conjugated bilirubin levels more than 2 times upper limit of normal (ULN) AND Alkaline phosphatase (ALP) and / or Gamma glutamyl transferase (GGT) more than 2 times upper limit of normal (ULN)] at screening visit will be considered for the study.
After confirming the inclusion/exclusion criteria the subject will be randomized and provided with study drug at randomization visit. Subjects will be provided with patient diary at randomization visit, which need to be brought along with in each subsequent visit till the last visit. Follow up visits will be done on week 1/day 8(±1) and week 2/day 15(±2) (Final Visit) of treatment to assess efficacy, safety and tolerability.
Patients will be assigned to either of the two arms i.e., Arm A or Arm B consisting of Ademetionine 1,4-Butane Disulfonate 500 mg Lyophilized Powder for Injection (Arm A) or Ademetionine-1,4-Butanedisulfonate Tablets 400 mg (Arm B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male and female patients aged between 18 to 65 years (both inclusive).
- •Patients with diagnosis of intrahepatic cholestasis (IHC): Serum total bilirubin and serum conjugated bilirubin levels more than 2 times upper limit of normal (ULN).
- •Alkaline phosphatase (ALP) and / or Gamma glutamyl transferase (GGT) more than 2 times upper limit of normal (ULN).
- •Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study.
- •WOCBP must have a negative urine pregnancy test at screening / baseline visit.
- •Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
- •Patients willing to comply with the protocol requirements.
排除标准
- •Patients with a known hypersensitivity to the active substance of Ademetionine.
- •Patients with a history of consumption of steatogenic medications in the 6 months prior to screening, such as Amiodarone, Methotrexate, Tamoxifen, Valproate, anti-retroviral medicine, NSAIDs, statins, neuroleptics, anti-convulsants, corticosteroids, etc.
- •as per available records.
- •Patients with a history of other causes of chronic liver disease (NAFLD, autoimmune liver diseases, viral hepatitis (Hepatitis B virus and Hepatitis C virus), Wilson’s disease, hemochromatosis) and metabolic syndrome.
- •Patients with a history of severe liver disease such as with Child-Pugh Class B or C and with any end-stage liver disease.
- •Patients with known or history of genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase deficiency, Vitamin B12 metabolism defect) or known folate, Vitamin B6 or B12 deficiency).
- •Patients with renal dysfunction (serum creatinine ≥ 2.5 mg/dL).
- •Patients with history of liver transplantation.
- •Patients with a history of active heavy alcohol intake (Greater than 150 g/day).
- •Patients who require ICU setting management.
- •Patients on any treatment with other drugs claimed for treatment of alcoholic liver disease (i.e., Pentoxyphylline, steroids, Ursodeoxycholic Acid, acetyl cholinesterase enzyme inhibitors antioxidants such as Vitamin E, Vitamin C, GSH, alpha-tocopherol, or non-prescribed complementary alternative medications [including dietary supplements]).
- •Patients with extrahepatic cause of cholestasis (proven by ultrasound or described in medical history).
- •Patients with a history of active substance abuse (oral, inhaled or injected) within one year prior to the study.
- •Patients on total parenteral nutrition in the year prior to screening.
- •Patients after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery).
- •Patients with any of the following disease in medical history: Evidence of autoimmune liver disease Wilson’s disease Hemochromatosis Alpha-1-antitrypsin deficiency
- •Patients with a history of biliary diversion.
- •Patients with a history of major depression or bipolar disease.
- •Patients with a known case of clinically significant cerebrovascular disease, cardiovascular disease, thyroid dysfunction, chronic uncontrolled systemic diseases like asthma, hypertension, collagen disorders, severe infections, that may affect patient safety.
- •Patients with any abnormality on 12-lead ECG at screening that in the opinion of the investigator is clinically significant and is judged as potential risk for patient’s participation in the study.
- •Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
- •Female patients who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (like hormonal, barrier methods or intrauterine device).
- •Patients with a history of any malignancy.
- •Patients with history of ascites, hepatic encephalopathy, varices or bleeding.
- •Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
- •Patients currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
- •Patients with suspected inability or unwillingness to comply with the study procedures.
- •Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient.
结局指标
主要结局
Mean change in serum total bilirubin and serum conjugated bilirubin from baseline to end of the study visit (week 2).
时间窗: Visit 1 - Screening or Baseline visit (Day -3), | Visit 3 - Follow up visit / week 1 (Day 8±1) and | Visit 4 - End of the study visit / Week 2 (Day 15±2).
次要结局
- Mean change in alkaline phosphatase (ALP) from baseline to end of the study visit (week 2).(Visit 1 - Screening or Baseline visit (Day -3),)
- Mean change in gamma glutamyl transferase (GGT) from baseline to end of the study visit (week 2).(Visit 1 - Screening or Baseline visit (Day -3),)
- Mean change in hepatic transaminases (i.e., SGOT and SGPT) from baseline to end of the study visit (week 2).(Visit 1 - Screening or Baseline visit (Day -3),)
- Changes in clinical symptoms of cholestasis (pruritus, fatigue and jaundice) as assessed by the investigator from baseline to end of the study visit (week 2).(Visit 1 - Screening or Baseline visit (Day -3),)
- Adverse events or Serious adverse events reported during the study.(Throughout the study)
- Changes in clinical laboratory parameters from baseline to end of the study visit (week 2).(Visit 1 - Screening or Baseline visit (Day -3) and)
研究者
Dr Rajasekhara Reddy Tamma
Clinwave Research Pvt. Ltd.