Saroglitazar 4 mg in treatment of Non-Alcoholic Steatohepatitis
- Conditions
- Health Condition 1: null- Nonalcoholic SteatohepatitisHealth Condition 2: K758- Other specified inflammatory liverdiseases
- Registration Number
- CTRI/2015/10/006236
- Lead Sponsor
- Cadila Healthcare Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Patients provide written informed consent for participation in this trial.
Male or female, aged from 18 to 75 years
Female must be either of non-child bearing potential (surgically sterilized at least 6 months prior to screening or postmenopausal) or using one or more methods of contraception.
Histologic confirmation of NASH without cirrhosis (fibrosis stage 1, 2, or 3) from liver biopsy performed either during the Screening period or within 6 months prior to the first visit with a NAS of >= 4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning). If biopsy is done within 6 months, the slides, biopsy material or block should be available for baseline documentation. Such patients, whose historical biopsy report available, should not use medications suspected of having an effect on NASH from the 3 months prior to the biopsy.
For hypertensive patients, blood pressure must be controlled by stable dose of anti hypertensive medications for at least 2 months prior to biopsy (and the stable dose can be maintained throughout the study)
Patients agree to comply with the study procedure.
Pregnancy and lactating female.
Positive pregnancy test.
Patients with history of myopathies or evidence of active muscle diseases
Patients with history of alcohol consumption of > 30 gm/week for men, >20 gm/week for women for 3 consecutive months in the last 5 years and/or drug abuse.
Known allergy, sensitivity or intolerance to the study drug, placebo, or formulation ingredients.
Participation in any other clinical trial in past 3 months other than survey based studies.
History of malignancy in the past 5 years and/or active neoplasm with the exception of superficial, non-melanoma, skin cancer.
Patients having unstable angina, Acute Myocardial Infarction in past 3 months or heart failure of NYHA class (III-IV).
New or worsening symptoms of coronary heart disease within the past three months or has any of the following within the past 6 months: ACS, worsening congestive heart failure (CHF), coronary artery intervention, stroke or Transient Ischemic Attack.
Previous history of bladder disease and/or hematuria. Current hematuria except due to Urinary Tract Infection.
Previous liver biopsy that demonstrated presence of cirrhosis or radiologic imaging consistent with cirrhosis or portal hypertension.
Type 2 diabetes treated with agents other than Metformin, sulfonylureas and DPP4 inhibitors.
Type 1 diabetes mellitus.
Patient on Fibrates (Other anti-dyslipidemic drugs will be allowed provided dose is stable in last 3 months before biopsy and the stable dose can be maintained throughout the study).
Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the 1 year prior to start of the study; (these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens, valproate/valproic acid, chloroquine, anti-HIV drugs).
History of thyroid disease. Hypothyroid patients who are euthyroid on thyroid hormone replacement can be included.
Uncontrolled Hypertension ( >140 mmHg Systolic and / or >90 mmHg Diastolic).
History of, or current cardiac dysrhythmias.
History of bariatric surgery, or undergoing evaluation for bariatric surgery.
Patients on weight loss regimen (>=5% weight loss) in last 8 weeks prior to diagnostic liver biopsy.
History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, or active gastrointestinal conditions that might interfere with drug absorption).
Patient on any treatment with other drugs used for treatment of NASH [Pentoxyphyllin, Ursodeoxycholic acid, antioxidants such as vitamin E ( >400IU/day), glutathione, Orlistat, Betaine, incretin mimetics or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas)] or any medicine in clinical trials for NASH [6].
History of other cause of chronic liver disease [autoimmune, primary biliary cirrhosis, hepatitis B virus (HBV) and hepatitis C virus (HCV), Wilson, alpha-1-antitrypsin deficit, hemochromatosis etc.] i.e. Antinuclear antibodies (ANA) > 1:160, Anti-smooth muscle Ab positive >1:160 , Serum hepatitis B surface antigen (HepBsAg) posit
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the decrease in NAFLD Activity Score (Time frame 52 weeks) <br/ ><br>Define by patients with NASH after 52 weeks of treatment Saroglitazar will show a decrease in NAFLD Activity Score (NAS) by at least 2 points spread across at least 2 of the NAS components [steatosis, hepatocyte ballooning, and lobular inflammation] with no worsening of fibrosis in greater proportion of patients compared to placebo. <br/ ><br>Timepoint: 52 weeks
- Secondary Outcome Measures
Name Time Method 1.Percentage of responders, defined by the disappearance of steatohepatitis <br/ ><br>2.Stage of steatosis, lobular inflammation and ballooning <br/ ><br>3.Stage of fibrosis Area of fibrosis <br/ ><br>4.Liver function test <br/ ><br>5.Lipid profile and lipoprotein <br/ ><br>6.Insulin resistance and glycemic control <br/ ><br>Timepoint: 52 weeks