Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Mg in Patients With Primary Biliary Cholangitis

Primary Biliary Cirrhosis Clinical Trial

— EPICS  

Official title:

A Phase 2, Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Magnesium in Patients With Primary Biliary Cholangitis (EPICS )

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03112681
• Other study ID #: SARO.16.004
• Status: Completed
• Phase: Phase 2
• Start date: August 18, 2017
• Est. completion date: August 7, 2020

Study information

• Verified date: December 2023
• Source: Zydus Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis. A total 36 subjects will be enrolled in a ratio of 1:1:1 to receive either saroglitazar magnesium 2 mg or saroglitazar magnesium 4 mg or placebo.

Description:

Study SARO.16.004.02 is a prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis.

A total 36 subjects will be enrolled in a ratio of 1:1:1 to receive either saroglitazar magnesium 2 mg or saroglitazar magnesium 4 mg or placebo. The primary objective is to investigate the effect of a 16-week treatment regimen of Saroglitazar magnesium 2 mg and 4 mg on ALP levels in patients with Primary Biliary Cholangitis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: August 7, 2020
• Est. primary completion date: August 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Males or females, between 18 and 75 years of age, inclusive.

2. a) Patients on therapeutic doses of Ursodeoxycholic acid (UDCA) for =12 months and stable therapy for =3 months prior to enrolment.

OR b) Patients who are unable to tolerate UDCA, and did not receive UDCA for at least 3 months from the date of screening.

3. History of confirmed Primary Biliary Cholangitis Diagnosis, based on American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009], as demonstrated by the presence of at least=2 of the following 3 diagnostic factors:

• History of elevated Alkaline Phosphatase levels for at least 6 months prior to Screening Visit 1

• Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) 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 =1.67x upper limit of normal (ULN) at Visit 1 and Visit 2 and with < 30% variance between the levels from Visit 1 to Visit 2.

5. Contraception: Female patients must be postmenopausal, surgically sterile, or if premenopausal, agree to use = 1 effective method of contraception during the trial. Effective methods of contraception are considered to be Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection); or Double barrier method, i.e., (a) condom (male or female) or (b) diaphragm, with spermicide; or Intrauterine device (IUD); or Vasectomy (partner).

6. Must provide written informed consent and agree to comply with the trial protocol.

Exclusion Criteria:

1. Consumption of >3 units of alcohol per day (>21 units per week) if male and >2 units of alcohol per day (>14 units per week) if female for at least 3 consecutive months in the last 5 years (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 including:

• Hepatitis B or C virus (HCV, HBV) infection

• Primary sclerosing cholangitis (PSC)

• Alcoholic liver disease

• Definite autoimmune liver disease or overlap syndrome

• Non-alcoholic steatohepatitis (NASH)

3. Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN, ascites, encephalopathy, known esophageal varices or history of variceal bleeding and active or history of hepatorenal syndrome.

4. History of any venous thromboembolism, TIA, intracranial hemorrhage, neoplasm, arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or screening blood tests that indicate altered coagulability (e.g. platelet count, aPTT, PTT or TT tests).

5. Patients with INR > ULN at visit 1.

6. Patients with total bilirubin > ULN at visit 1 that is not due to Gilbert's syndrome

7. Patients with >30% increase in ALT, total bilirubin, or INR between Visit 1 to Visit 2.

8. Patients with serum creatinine >ULN according to the gender at Visit 1.

9. Patients with abnormal total creatine kinase (CK) OR lipase OR amylase at Visit 1.

10. Unstable cardiovascular disease, including:

• unstable angina, (i.e., new or worsening symptoms of coronary heart disease within the past 3 months), acute coronary syndrome within the past 6 months, acute myocardial infarction in the past 3 months or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, within the past 6 months

• history of (within prior 3 months) or current unstable cardiac dysrhythmias

• uncontrolled hypertension (systolic blood pressure [BP] >160 mmHg and/or diastolic BP >100 mmHg)

• stroke or transient ischemic attack within the prior 6 months

11. History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.

12. Contraindications to Saroglitazar magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar magnesium.

13. Known allergy, sensitivity or intolerance to the study drug, comparator or formulation ingredients.

14. Participation in any other clinical study within the previous 3 months of screening.

15. Illicit substance abuse within the past 6 months.

16. 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, human immunodeficiency virus (HIV), coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption).

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

Drug:
• Saroglitazar magnesium 2 mg
Saroglitazar magnesium 2 mg once daily in the morning before breakfast without food, for a period of 16 weeks.
• Saroglitazar magnesium 4 mg
Saroglitazar magnesium 4 mg once daily in the morning before breakfast without food, for a period of 16 weeks.
• Placebo Oral Tablet
Placebo once daily in the morning before breakfast without food, for a period of 16 weeks.

Locations

Country	Name	City	State
United States	Carolinas Healthcare System	Charlotte	North Carolina
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Gastrointestional Specialists of Georgia	Marietta	Georgia
United States	Schiff Center for Liver Diseases/University of Miami	Miami	Florida
United States	Rutgers NJ Medical School	Newark	New Jersey
United States	California Liver Research Institute	Pasadena	California
United States	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Zydus Therapeutics Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available. — View Citation

Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available. — View Citation

Vuppalanchi R, Caldwell SH, Pyrsopoulos N, deLemos AS, Rossi S, Levy C, Goldberg DS, Mena EA, Sheikh A, Ravinuthala R, Shaikh F, Bainbridge JD, Parmar DV, Chalasani NP. Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of a 16-week treatment regimen of Saroglitazar magnesium 2 mg and 4 mg on ALP levels in patients with Primary Biliary Cholangitis.	Improvement in ALP levels after 16 weeks of Saroglitazar magnesium 2 mg and 4 mg treatment.	16 Weeks

External Links

•   European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases.
•   Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis.
•   Vuppalanchi R, Caldwell SH, Pyrsopoulos N, deLemos AS, Rossi S, Levy C, Goldberg DS. Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients