CTRI/2024/12/078394 [Registered on: 20/12/2024] Trial Registered Prospectively
Last Modified On:
02/12/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to assess the efficacy and safety of Ademetionine Injection in patients with bile flow problems inside the liver.
Scientific Title of Study
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).
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CT/2024/26, Version No.: 00 and Dated May 01, 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
LIG: B/466, H. No.: 1-16-10/466, Dr. A.S. Rao Nagar, Kapra, Medchal-Malkajgiri (Dist.).
Medchal TELANGANA 500062 India
Phone
7989233379
Fax
Email
dr.sekhar@clinwave.co.in
Details of Contact Person Scientific Query
Name
Dr Harsh Shah
Designation
AGM - Medical Affair & Pharmacovigilance
Affiliation
La Renon Healthcare Pvt. Ltd.
Address
207-208, ISCON Elegance, Circle P, Prahaldnagar Crossroads, SG Highway.
Ahmadabad GUJARAT 380015 India
Phone
9879540270
Fax
Email
harsh.shah@larenon.com
Details of Contact Person Public Query
Name
Dr Harsh Shah
Designation
AGM - Medical Affair & Pharmacovigilance
Affiliation
La Renon Healthcare Pvt. Ltd.
Address
207-208, ISCON Elegance, Circle P, Prahaldnagar Crossroads, SG Highway.
Ahmadabad GUJARAT 380015 India
Phone
9879540270
Fax
Email
harsh.shah@larenon.com
Source of Monetary or Material Support
La Renon Healthcare Pvt. Ltd., 207-208, ISCON Elegance, Circle P, Prahaldnagar Crossroads, SG Highway, Ahmedabad-380015, Gujarat, India.
Primary Sponsor
Name
La Renon Healthcare Pvt. Ltd.
Address
207-208, ISCON Elegance, Circle P, Prahaldnagar Crossroads, SG Highway, Ahmedabad-380015, Gujarat, India.
Ademetionine 1,4-Butane Disulfonate 500 mg Lyophilized Powder for Injection
The recommended dosing is 5-12 mg/kg/day IV or IM. The usual starting dose is 500 mg/day IV or IM for 2 weeks.
Comparator Agent
Ademetionine-1,4-Butanedisulfonate Tablets 400 mg
one tablet thrice a day orally, swallowed with water in the morning, afternoon and evening around same time every day for 2 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male and female patients aged between 18 to 65 years (both inclusive).
2. 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).
3. 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.
4. Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
5. Patients willing to comply with the protocol requirements.
ExclusionCriteria
Details
1. Patients with a known hypersensitivity to the active substance of Ademetionine.
2. 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.
3. 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.
4. Patients with a history of severe liver disease such as with Child-Pugh Class B or C and with any end-stage liver disease.
5. 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).
6. Patients with renal dysfunction (serum creatinine ≥ 2.5 mg/dL).
7. Patients with history of liver transplantation.
8. Patients with a history of active heavy alcohol intake (Greater than 150 g/day).
9. Patients who require ICU setting management.
10. 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]).
11. Patients with extrahepatic cause of cholestasis (proven by ultrasound or described in medical history).
12. Patients with a history of active substance abuse (oral, inhaled or injected) within one year prior to the study.
13. Patients on total parenteral nutrition in the year prior to screening.
14. Patients after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery).
15. Patients with any of the following disease in medical history:
Evidence of autoimmune liver disease
Wilson’s disease
Hemochromatosis
Alpha-1-antitrypsin deficiency
16. Patients with a history of biliary diversion.
17. Patients with a history of major depression or bipolar disease.
18. 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.
19. 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.
20. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
21. 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).
22. Patients with a history of any malignancy.
23. Patients with history of ascites, hepatic encephalopathy, varices or bleeding.
24. Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
25. Patients currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
26. Patients with suspected inability or unwillingness to comply with the study procedures.
27. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Mean change in serum total bilirubin and serum conjugated bilirubin from baseline to end of the study visit (week 2).
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).
Secondary Outcome
Outcome
TimePoints
Mean change in alkaline phosphatase (ALP) from baseline to end of the study visit (week 2).
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).
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),
Visit 3 - Follow up visit / week 1 (Day 8±1) and
Visit 4 - End of the study visit / Week 2 (Day 15±2).
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),
Visit 3 - Follow up visit / week 1 (Day 8±1) and
Visit 4 - End of the study visit / Week 2 (Day 15±2).
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),
Visit 3 - Follow up visit / week 1 (Day 8±1) and
Visit 4 - End of the study visit / Week 2 (Day 15±2).
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
Visit 4 - End of the study visit / Week 2 (Day 15±2).
Target Sample Size
Total Sample Size="180" Sample Size from India="180" Final Enrollment numbers achieved (Total)= "180" Final Enrollment numbers achieved (India)="180"
Phase of Trial
Phase 3
Date of First Enrollment (India)
06/01/2025
Date of Study Completion (India)
16/10/2025
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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).