Saroglitazar Magnesium for Treatment of Primary Biliary Cholangitis

Recruitment Status
COMPLETED
(See Contacts and Locations)Verified March 2026 by Zydus Therapeutics Inc.
Sponsor
Zydus Therapeutics Inc.
Information Provided by (Responsible Party)
Zydus Therapeutics Inc.
Clinicaltrials.gov Identifier
NCT05133336
Other Study ID Numbers:
SARO.21.001
First Submitted
October 31, 2021
First Posted
November 23, 2021
Last Update Posted
April 29, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

A Multicenter, Randomized, Double-blind, Placebo controlled, Phase 2b/3 Study to Evaluate the Efficacy and Safety of Saroglitazar Magnesium in Subjects with Primary Biliary Cholangitis

Condition or DiseaseIntervention/Treatment
Primary Biliary Cholangitis
Drug: Saroglitazar Magnesium 1 mgDrug: Saroglitazar Magnesium 1 mgDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment196 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 2b/3 Study to Evaluate the Efficacy and Safety of Saroglitazar Magnesium in Subjects With Primary Biliary Cholangitis
Study Start DateMarch 31, 2022
Actual Primary Completion DateApril 29, 2025
Actual Study Completion DateMay 6, 2025

Groups and Cohorts

Group/CohortIntervention/Treatment
Saroglitazar Magnesium 2 mg
Subjects who received Saroglitazar Magnesium 2 mg tablet orally administered once daily in the morning before breakfast are switched to Saroglitazar Magnesium 1 mg for remaining of the treatment period
Drug: Saroglitazar Magnesium 1 mg
Subjects randomized to Saroglitazar Magnesium 1 mg arm will receive Saroglitazar Magnesium 1 mg treatment for the entire treatment period up to Week 52.
Saroglitazar Magnesium 1 mg
Saroglitazar Magnesium 1 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (52 weeks).
Drug: Saroglitazar Magnesium 1 mg
Subjects randomized to Saroglitazar Magnesium 1 mg arm will receive Saroglitazar Magnesium 1 mg treatment for the entire treatment period up to Week 52.
Placebo
Placebo tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (52 weeks).
Drug: Placebo
Subjects randomized to placebo arm will receive placebo treatment for the entire treatment period up to Week 52.

Outcome Measures

Primary Outcome Measures
  1. Proportion of subjects with biochemical response based on the composite endpoints of ALP and total bilirubin
    ALP \< 1.67 x ULN, ≥ 15% decrease in ALP relative to baseline, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in subjects with known Gilbert's syndrome
Secondary Outcome Measures
  1. Proportion of subjects with complete normalization of ALP.
    ALP≤ULN
  2. Pruritis assessed by 5 D itch scales
    Change from baseline in 5-D itch score
  3. Proportion of subjects with biochemical response based on the composite endpoints of ALP and total bilirubin
    ALP \< 1.67 x ULN, ≥ 15% decrease in ALP, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in subjects with known Gilbert's syndrome
  4. Proportion of subjects change from baseline in ALP
    ALP improvement of at least 15%, 30%, 40%, and 50% Absolute and percent change from baseline in ALP values
  5. Quality of life assessed by the PBC 40 questionnaire
    Change from baseline in quality of life (PBC 40) questionnaire domains (total score and domain score)
  6. Improvement in liver stiffness measurement (LSM) of at least 25% relative to baseline assessed by Liver elastography/FibroScan®
    Proportion of subjects with a decrease in LSM of at least 25%
  7. To effect on liver enzymes
    Change from baseline in liver enzyme parameters (ALT, AST, GGT, and total bilirubin \[direct and indirect bilirubin\])
  8. The effect on liver enzymes
    Change from baseline in serum bile acids
  9. The effect on lipid parameters
    Change from baseline in lipid parameters (TG, LDL-C, HDL-C, VLDL-C, total cholesterol, and non-HDL-C)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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
Positive anti-mitochondrial antibodies (AMA) titer OR positive PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components \[PDC-E2, 2-oxo-glutaric acid dehydrogenase complex\]) if AMA is negative
Liver biopsy consistent with PBC 4. ALP ≥ 1.67 x ULN at both Visits 1 and 2 and \< 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.
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 (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor). 2. History or presence of other concomitant liver diseases at screening: 1. Chronic hepatitis B or C virus (HBV, HCV) infection. (Note: However, If the subject has been treated for the HCV infection and has been cured for a duration of more than 2 years from screening, such subjects can be enrolled in the study) 2. Primary sclerosing cholangitis (PSC). 3. Alcoholic liver disease. 4. Autoimmune hepatitis (AIH) indicative of PBC with overlap syndrome. Note: The Paris criteria are commonly used to define the presence of PBC with features of AIH and have been endorsed by EASL and AASLD. According to these criteria, a diagnosis can be made in a patient with PBC as follows: At least two of the following: I. ALP \> 2 x ULN or GGT \> 5 x ULN. II. AMA positive III. Florid bile duct lesion on histology. AND At least two of the following three features: I. ALT \> 5 x ULN. II. Immunoglobulin G serum levels \> 2 x ULN or smooth muscle autoantibody positive. III. Moderate to severe interface hepatitis on histology. e. Hemochromatosis. f. Non-alcoholic steatohepatitis (NASH) on historical biopsy. 3.Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, ascites requiring treatment, encephalopathy, known large esophageal varices or history of variceal bleeding within one year prior to screening or history of hepatorenal syndrome. 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 α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening). 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 - 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 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. 14.History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 x ULN at screening. 15.Subjects whose ALT, AST, or ALP exceeds by more than 50% on Visit 2 reading compared to Visit 1. Note: If the ALT, AST, or ALP values on Visit 2 exceed by more than 50% from Visit 1, then a third value will be measured (within 1- 2 weeks) to assess for the trend. If the third value shows continued increase ≥ 10%, then subject is considered ineligible for randomization. 16.Any of the following laboratory values at screening: a. Platelets \< 50 × 109/L b. Albumin \< 2.8 g/dL c. eGFR \< 45 mL/min/1.73 m2 d. ALP \> 10 x ULN e. ALT or AST \> 250 U/L 17.Participation in another interventional clinical study and receipt of any other investigational medication (within 12 weeks prior to randomization up to end of study). 18.History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial non-melanoma skin cancer. 19.Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium. 20.Known allergy, sensitivity, or intolerance to the study drug, comparator, or formulation ingredients. 21.Pregnancy-related exclusions, including: a. Pregnant/lactating female (including positive pregnancy test at screening). b. Pregnancy should be avoided by male and female subjects 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 treatment. Refer Appendix 8 Contraceptive Guidance 22.History or other evidence of severe illness or any other conditions that would make the subject, 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). 23.Cirrhosis with Child-Pugh-Turcotte (CPT) Class B or C having score of 7 or above at screening 24.Subjects with Model for End Stage Liver Disease (MELD 3.0) score of 12 or above

Contacts and Locations

Sponsors and CollaboratorsZydus Therapeutics Inc.
Locations
Zydus US007 | Birmingham Alabama, United States, 35294Zydus US021 | Tucson Arizona, United States, 85724Zydus US013 | Los Angeles California, United States, 90048Zydus US011 | Pasadena California, United States, 91105Zydus US043 | Sacramento California, United States, 95817Zydus US022 | Aurora Colorado, United States, 80045Zydus US037 | New Haven Connecticut, United States, 06510Zydus US027 | Jacksonville Florida, United States, 32224Zydus US006 | Lakewood Rch Florida, United States, 34211Zydus US005 | Miami Florida, United States, 33136Zydus US028 | Sarasota Florida, United States, 34240Zydus US019 | Tampa Florida, United States, 33606Zydus US020 | Marietta Georgia, United States, 30060Zydus US001 | Indianapolis Indiana, United States, 46202Zydus US034 | Iowa City Iowa, United States, 52242Zydus US036 | Marrero Louisiana, United States, 70072Zydus US023 | Rochester Minnesota, United States, 55905Zydus US030 | St Louis Missouri, United States, 63104Zydus US024 | Omaha Nebraska, United States, 68105Zydus US038 | Manhasset New York, United States, 11030Zydus US035 | Rochester New York, United States, 14642Zydus US002 | Charlotte North Carolina, United States, 28204Zydus US014 | Cincinnati Ohio, United States, 45044Zydus US015 | Philadelphia Pennsylvania, United States, 19141Zydus US004 | Houston Texas, United States, 77030Zydus US042 | Houston Texas, United States, 77030Zydus US031 | Murray Utah, United States, 84107Zydus US016 | Charlottesville Virginia, United States, 22908Zydus US041 | Newport News Virginia, United States, 23602Zydus US039 | Richmond Virginia, United States, 23219Zydus US033 | Seattle Washington, United States, 98105Zydus AR004 | Buenos Aires , Argentina, B1629ODTZydus AR009 | Buenos Aires , Argentina, B7600FZOZydus AR001 | Buenos Aires , Argentina, C1118AATZydus AR005 | Buenos Aires , Argentina, C1125ABEZydus AR013 | Buenos Aires , Argentina, C1180AAXZydus AR007 | Buenos Aires , Argentina, C1199ABBZydus AR006 | Buenos Aires , Argentina, C1221ADCZydus AR012 | Buenos Aires , Argentina, C1426ABPZydus AR003 | Buenos Aires , Argentina, C1430CKEZydus AR010 | Santa Fe , Argentina, S2002KDSZydus IS001 | Reykjavik , Iceland, IS-101Zydus TR014 | Adana , Turkey (Türkiye), 01790Zydus TR016 | Altındağ , Turkey (Türkiye), 06230Zydus TR004 | Ankara , Turkey (Türkiye), 06800Zydus TR005 | Bursa , Turkey (Türkiye), 16059Zydus TR017 | Cebeli , Turkey (Türkiye), 06620Zydus TR008 | Gaziantep , Turkey (Türkiye), 27080Zydus TR009 | Istanbul , Turkey (Türkiye), 34093Zydus TR010 | Istanbul , Turkey (Türkiye), 34098Zydus TR003 | Istanbul , Turkey (Türkiye), 34764Zydus TR001 | Istanbul , Turkey (Türkiye), 34899Zydus TR002 | Izmir , Turkey (Türkiye), 35100Zydus TR013 | Izmir , Turkey (Türkiye), 35150Zydus TR011 | Kocaeli , Turkey (Türkiye), 41380Zydus TR015 | Melikgazi , Turkey (Türkiye), 38030Zydus TR006 | Mersin , Turkey (Türkiye), 33110
Investigators
Study Director: Deven V Parmar, MD, Zydus Therapeutics Inc.