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

NCT03112681 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SARO.16.004
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 9

Brief 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 (PBC). 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.

Conditions

Primary Biliary Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Effect of a 16-week Treatment Regimen of Saroglitazar Magnesium 2 mg and 4 mg on Alkaline Phosphatase (ALP) Levels in Patients With Primary Biliary Cholangitis.

  Change in ALP levels after 16 weeks of Saroglitazar magnesium 2 mg and 4 mg treatment.

  Baseline and Week 16

Study Arms (3)

Saroglitazar magnesium 2 mg

EXPERIMENTAL

Saroglitazar magnesium 2 mg tablet Once daily for 16 weeks

Drug: Saroglitazar magnesium 2 mg

Saroglitazar magnesium 4 mg

EXPERIMENTAL

Saroglitazar magnesium 4 mg tablet Once daily for 16 weeks

Drug: Saroglitazar magnesium 4 mg

Placebo

PLACEBO COMPARATOR

Placebo tablet Once daily for 16 weeks

Drug: Placebo Oral Tablet

Interventions

Saroglitazar magnesium 2 mg DRUG

Saroglitazar magnesium 2 mg once daily in the morning before breakfast without food, for a period of 16 weeks.

Also known as: Not any

Saroglitazar magnesium 2 mg

Saroglitazar magnesium 4 mg DRUG

Saroglitazar magnesium 4 mg once daily in the morning before breakfast without food, for a period of 16 weeks.

Also known as: Not any

Saroglitazar magnesium 4 mg

Placebo Oral Tablet DRUG

Placebo once daily in the morning before breakfast without food, for a period of 16 weeks.

Also known as: Not any

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, between 18 and 75 years of age, inclusive.
• 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.
• 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.
• 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.
• 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).
• Must provide written informed consent and agree to comply with the trial protocol.

You may not qualify if:

• 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).
• 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)
• 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.
• History of any venous thromboembolism, transient ischemic attack (TIA), intracranial hemorrhage, neoplasm, arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or screening blood tests that indicate altered coagulability (e.g. platelet count, activated partial thromboplastin time \[aPTT\], partial thromboplastin time \[PTT\] or thrombin time \[TT\] tests).
• Patients with INR \> upper limit of normal (ULN) at visit 1.
• Patients with total bilirubin \> ULN at visit 1 that is not due to Gilbert's syndrome
• Patients with \>30% increase in ALT, total bilirubin, or Internation normalized ratio (INR) between Visit 1 to Visit 2.
• Patients with serum creatinine \>ULN according to the gender at Visit 1.
• Patients with abnormal total creatine kinase (CK) OR lipase OR amylase at Visit 1.
• Unstable cardiovascular disease, including:

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (9)

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Gastrointestional Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Rutgers NJ Medical School

Newark, New Jersey, 07101, United States

Location

Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45249, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Einstein Medical Center Philadelphia

Philadelphia, Pennsylvania, 19141, United States

Location

Related Publications (4)

• 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.

  PMID: 19501929 BACKGROUND

• 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.

  PMID: 19554543 BACKGROUND

• 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 with primary biliary cholangitis. J Hepatol. 2022 Jan;76(1):75-85. doi: 10.1016/j.jhep.2021.08.025. Epub 2021 Sep 4.

  PMID: 34487750 RESULT

• Vuppalanchi R, Gonzalez-Huezo MS, Payan-Olivas R, Munoz-Espinosa LE, Shaikh F, Pio Cruz-Lopez JL, Parmar D. A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis. Clin Transl Gastroenterol. 2021 Mar 26;12(4):e00327. doi: 10.14309/ctg.0000000000000327.

  PMID: 33769355 DERIVED

Related 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

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

saroglitazar

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Deven Parmar
• Organization: Zydus Therapeutics Inc.

dparmar@zydustherapeutics.com

7324050886

Study Officials

• Deven Parmar, MD FACP FCP

  Zydus Therapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 13, 2017
• Study Start: August 18, 2017
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

US (9)