Open-Label Extension Study of Saroglitazar Magnesium in Participants with Primary Biliary Cholangitis

Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis

A Multicenter, Open-Label, Extension Clinical trial to evaluate Safety and Efficacy of Saroglitazar Magnesium in Participants with Primary Biliary Cholangitis (PBC)

Eligibility Criteria:
Inclusion Criteria:

1. Must provide written informed consent and agree to comply with the trial protocol
2. Participated and completed SARO.21.001, the double-blind treatment phase study

Exclusion Criteria:

1. Consumption of 2 standard drinks per day if male and 1 standard drink per day if female for 3 consecutive months (12 consecutive weeks) throughout double-blind phase till screening.
2. Participants with MELD 3.0 score of 15 or greater
3. History or presence of other concomitant liver diseases at screening:

   1. Chronic hepatitis B or C virus (HBV, HCV) infection
   2. Primary sclerosing cholangitis (PSC)
   3. Alcoholic liver disease
   4. Autoimmune hepatitis (AIH)-PBC overlap syndrome
   5. Hemochromatosis
   6. Non-alcoholic steatohepatitis (NASH) on historical biopsy
4. Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, uncontrolled ascites, encephalopathy, history of variceal bleeding or history of hepatorenal syndrome at screening.
5. Use of Thiazolidinediones or Fibrates (within 12 weeks prior to screening)
6. Use of other PPAR agonists (i.e., Elafibranor, Seladelpar), Obeticholic acid (OCA), methotrexate, budesonide and other systemic corticosteroids (Prednisone dose more than 10 mg); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening)
7. 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
8. Unstable cardiovascular disease, including:

   1. 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 - IV) or worsening congestive heart failure, or coronary artery intervention, in the 24 weeks before screening and throughout the screening period
   2. History/current unstable cardiac dysrhythmias
   3. Uncontrolled hypertension at screening
   4. Stroke or transient ischemic attack in the 24 weeks before screening
9. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, and coagulation disorders
10. An uncontrolled thyroid disorder

    1. 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 continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e., methimazole or propylthiouracil) in the 24 weeks before screening
    2. Uncontrolled hypothyroidism: defined as initiation of thyroid hormone replacement therapy or dose adjustment of replacement therapy in the 12 weeks before screening
11. History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 × ULN at screening
12. Any of the following laboratory values:

    1. Total bilirubin \> 3 x ULN
    2. Platelets \< 50 × 103/mL
    3. Albumin \< 2.8 g/dL
    4. eGFR \< 45 mL/min/1.73 m2
    5. ALT or AST \> 250 U/L
    6. ALP \> 10 × ULN
13. Participation in another interventional clinical study and receipt of any other investigational medication or medical device within 30 days or within 5 half-lives, whatever is longer, prior to screening
14. History of malignancy in the past 5 years and/or active neoplasm which may diminish life expectancy (except resolved superficial non-melanoma skin cancer, carcinomas in situ or other stable, relatively benign conditions if appropriately treated prior to screening)
15. Known allergy, sensitivity or intolerance to the study medication or formulation ingredients
16. Pregnancy-related exclusions, including:

    1. Pregnant/lactating female (including positive pregnancy test at screening)
    2. Participants agree to avoid pregnancy either by true abstinence or the use of an acceptable effective contraceptive measures for the duration of the study and for at least 1 month after the end of the study medication. Refer Appendix 9 Contraceptive Guidance.
17. History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption)
18. Cirrhosis with Child-Pugh-Turcotte (CPT) class B or C having score of 7 or above at screening (Refer Appendix 11