Study to Evaluate Safety, Tolerability and Efficacy in patients with Primary Biliary Cholangitis of Saroglitazar Magnesium-III (EPICS-III).

Phase 1

Conditions: Primary biliary Cholangitis
MedDRA version: 27.0Level: PTClassification code 10080429Term: Primary biliary cholangitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2022-001634-10-IS

Lead Sponsor: Zydus Therapeutics Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 192

Inclusion Criteria

1. Males or females, between 18 and 75 years of age, both inclusive at screening.
2. Subjects on ursodeoxycholic acid (UDCA) for at least 12 months at a therapeutic dose (at least 13 mg/kg per day) and a stable dose for 6 months prior to Screening Visit and having ALP = 1.67 x ULN.
OR
Subjects who are unable to tolerate UDCA and did not receive UDCA for at least 3 months prior to the date of screening and having ALP = 1.67 x ULN.
3. History of confirmed PBC diagnosis, based on American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines, as demonstrated by the presence of at least = 2 of the following 3 diagnostic factors:
-History of elevated ALP levels for at least 6 months prior to screening
-The subjects should have positive anti-mitochondrial antibodies (AMA) titer OR if AMA is negative or in low titer (< 1:80), then the subjects should have PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
-Liver biopsy consistent with PBC
4. ALP = 1.67 x ULN at both Visits 1 and 2 and with < 30% variance between the levels from Visit 1 to Visit 2
5. Total bilirubin < 2 x ULN at screening (Visit 1)
6. Must provide written informed consent and agree to comply with the trial protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

1.Consumption of 2 standard alcohol drinks per day if male and 1 standard alcohol drink per day if female for at least 3 consecutive months (12 consecutive weeks) within 5 year before screening. 2.History or presence of other concomitant liver diseases at screening: a.Chronic hepatitis B or C virus (HBV, HCV) infection. b.Primary sclerosing cholangitis (PSC). c.Alcoholic liver disease. d.Autoimmune hepatitis (AIH) indicative of PBC with overlap syndrome. e.Hemochromatosis. f.Non-alcoholic steatohepatitis (NASH) on historical biopsy. 3.Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, encephalopathy, known large esophageal varices or history of variceal bleeding and active or history of hepatorenal syndrome at screening. 4.Clinically silent compensated cirrhosis (at screening), defined as (a) nodular liver contour by abdominal imaging with at least one sign of liver dysfunction (> ULN INR or < LLN serum albumin); or (b) prolonged INR (> ULN) and diminished albumin (< LLN); or (c) platelet count <140x109/L with INR > ULN or serum albumin < LLN. 5.Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers. 6.Use of thiazolidinediones or fibrates (within 12 weeks prior to screening) 7.Use of obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (Note: Prednisone dose should not be more than 10 mg per day); potentially hepatotoxic drugs (including a-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening) 8.Use of drugs that are known cytochromes P2C8 (CYP2C8) inhibitors/substrate within 4 weeks prior to screening (refer to Appendix 7 for List of Known CYP2C8 Inhibitors/Substrate).
9. History of bowel surgery (gastrointestinal [bariatric] surgery in the preceding 1 year or undergoing evaluation for gastrointestinal surgery (bariatric surgery for obesity, extensive small-bowel resection) or orthotopic liver transplant (OLT) or listed for OLT. 10.Type 1 diabetes mellitus
11. Unstable cardiovascular disease, including: a. Unstable angina, (i.e., new or worsening symptoms of coronary heart disease in the 12 weeks before screening and throughout the Screening Period), acute coronary syndrome in the 24 weeks before screening and throughout the Screening Period, acute myocardial infarction in the 12 weeks before screening and throughout the Screening Period or heart failure of New York Heart Association class (III to IV) or worsening congestive heart failure, or coronary artery intervention, in the 24 weeks before screening and throughout the Screening Period. b. History/current unstable cardiac dysrhythmias. c. Uncontrolled hypertension at screening. d. Stroke or transient ischemic attack in the 24 weeks before screening. 12. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, coagulation disorders, or screening blood tests that, in the opinion of the Investigator, indicate altered coagulability (e.g., PT, INR, aPTT) at screening. 13. An uncontrolled thyroid disorder a. Uncontrolled hyperthyroidism: defined as any history of hyperthyroidism that has either not been treated with either radioactive iodine and/or surgery or that has been treated with radioactive iodine and/or surgery, but has required ongoing c