To study effect of Livitol in treatment of patients diagnosed with moderate to severe non-alcoholic fatty liver.
Scientific Title of Study
A Randomized, Multicenter, Double-blinded, Parallel-group, Phase 2 Study to Evaluate Efficacy and Safety of Livitol among Patients with Moderate to Severe Non-alcoholic fatty liver [steatosis].
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
DRL-Livitol-2021 Protocol Version 1.0 / 27 Jan 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Ganesh H Divekar
Designation
Vice President - Clinical Operations, Biometrics and Medical Services
Patients will receive Livitol two tablets twice daily for 24 weeks.
Comparator Agent
Placebo
Patients will receive placebo two tablets twice daily 24 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Age 18-65 years at study entry.
2. Male, or female diagnosed with non-alcoholic fatty liver (steatosis), but if female, meets all the following criteria:
a. Not breastfeeding
b. Post-menopausal or negative urine pregnancy test result at Screening /Visit 1 (not required for hysterectomized females).
c. If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectables, oral contraceptives [must have been using for at least the last
3 months], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized partner) during the entire duration of the study.
3. Patients diagnosed with moderate to severe fatty liver based on ultrasound (if ultrasound is available within 3 months of screening, it would be considered valid for screening).
4. Patients with liver fat greater than 15% as measured by MRI-PDFF at Screening.
5. Can read, understand, and sign the informed consent form (ICF) and communicate with the investigator, and understand and comply with protocol requirements.
ExclusionCriteria
Details
1. eGFR less than 60ml/min/1.73m2 at screening (chronic kidney disease epidemiology collaboration [CKD-EPI] formula).
2. Elevation of AST or ALT greater than five times upper limit normal (ULN).
3. Evidence of significant alcohol consumption (defined as more than 7 drinks/week for females and greater than 14 drinks/week for males) within 6 months prior to randomization
4. Body Mass Index (BMI) more than or equal to 40 kg/m2
5. Use of any of the following medications in the last 12 weeks prior to screening visit:
a. Metformin greater than 2 g/day
b. Insulins – all forms
c. Use of sildenafil, tadalafil, vardenafil, pioglitazone, rosiglitazone, alpha blockers, oral nitrates.
d. Medications associated with increased hepatic steatosis.
Commonly used medications associated with drug induced hepatic steatosis include amiodarone, valproate, tamoxifen, methotrexate, and some chemotherapeutic and antiretroviral agents, and steroids.
e. Organic Cation Transporter 2/MATE inhibitors (Includes
multidrug and toxin extrusion protein 1 and multidrug and toxin
extrusion protein 2 inhibitors like:
i. Methotrexate
ii. Tamoxifen
f. Corticosteroids (Nasal steroids are allowed if the subject has been on a stable dose for the past 12 weeks and the dose employed does not exceed the maximal recommended dose)
g. Estrogens
h. Amiodarone
i. Valproic acid
j. Coumadin
k. Isoniazide
l. Nucleoside analogues used for the treatment of human
immunodeficiency virus (HIV) infections
m. Any dietary supplement including Vitamin E and L-Carnitine other than multi-vitamins.
6. Presence or suspicion of other forms of chronic liver disease (e.g., cirrhosis, autoimmune hepatitis (greater than 1 is to 160 Anti-Nuclear Antibody ANA), Wilsons disease, Hemochromatosis (Ferritin greater than 1000 ug/L and percent iron saturation
greater than 45 percent), hepatitis A, B or C), primary biliary cholangitis, primary sclerosing cholangitis, Wilsons disease, homozygous alpha 1 anti trypsin deficiency.
7. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:
a. Unable to undergo MRI or contraindications for MRI procedure
b. History of cardio or cerebro vascular disease event within the previous 6 months
c. Requires anti coagulation therapy
d. Gastrointestinal disorders including, but not limited to, the following:
pancreatitis, inflammatory bowel disease, or other diseases associated with malabsorption or persistent abdominal discomfort
e. Endocrine disorders, other than type 2 diabetes and hypothyroidism on stable replacement therapy for 3 months prior to enrolment.
f. Chronic infection (e.g., tuberculosis, HIV infection, hepatitis A virus, hepatitis B virus, or hepatitis C virus)
g. Neurological or psychiatric diseases that preclude valid execution of informed consent or may interfere with the subjects compliance with study procedures (e.g., major depressive disorder within the last 2 years, a history of suicidal behaviour in the last 3 months). This will be based on investigator’s opinion and does not need formal psychological screening.
h. History of other psychiatric disorders including schizophrenia and bipolar disorder only through clinical history and does not require a psychological screening.
8. Participation in a weight loss program within the past 3 months and /or weight change greater than or equal to 5 percent during the past month.
9. History of substance abuse (including alcohol abuse as defined above) in the past 3 months
10. Has received any investigational drug within 3 months of Screening.
11. Has donated blood within 3 months before Screening or is planning to donate blood during the study.
12. Has had a serious acute infection, such as pneumonia in the previous 12 weeks
13. Prior or planned (during the study period) bariatric surgery (e.g., gastroplasty, sleeve gastrectomy and roux-en-Y gastric bypass).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Hepatic Fat content
Baseline, Week 24
Secondary Outcome
Outcome
TimePoints
1. To evaluate the change from baseline in fatty liver grading using the 4 ultrasound criteria or signs
2. To evaluate the change in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
gamma-glutamyl transferase (GGT) levels
3. To evaluate the change in hemoglobin A1c / glycated hemoglobin (HbA1C), fasting glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR)
4. To evaluate the change in cholesterol, low density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and free fatty acid (FFA)
5. To evaluate the change in fibrosis-4 (FIB-4) score.
Secondary Safety Endpoints:
a. Adverse events
b. Serious adverse events
c. Significant changes in:
d. Vital signs
e. Physical examination findings
f. Laboratory derangements
g. Electrocardiogram (ECG) findings.
Baseline Week 12, Week 24
Target Sample Size
Total Sample Size="76" Sample Size from India="76" Final Enrollment numbers achieved (Total)= "76" Final Enrollment numbers achieved (India)="76"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a randomized, prospective, multicentre,
double-blind, placebo-controlled, parallel group Phase 2 study to assess
efficacy and safety of Livitol among patients with moderate to severe non-alcoholic
fatty liver (steatosis).
The study includes screening period (14 days) and
treatment period (24 weeks).
The study will include approximately 76 participants
at approximately 8-10 centres in India.
Prospective subjects who have ultrasonography report
confirming moderate to severe non-alcoholic fatty liver (steatosis) will be considered
for 14-day screening period to confirm the study eligibility. Ultrasonography
positive for moderate to severe fatty liver) is required prior to the baseline
MRI-PDFF. The eligible subjects will be randomized (1:1) to receive study drug
(Livitol) or placebo, and the treatment will be administered twice daily for
the duration of 24 weeks (6 months). The subjects will be evaluated at Week 4, 12
and 24.