Saroglitazar Magnesium in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis

NCT03061721 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SARO.16.005
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 18

Brief Summary

This is a randomized, double-blind, placebo-controlled study in up to 104 patients with a diagnosis of Non-alcoholic fatty Liver disease (NAFLD) and/or Non-alcoholic steatohepatitis (NASH). The study will be conducted over a period of up to 22 weeks and will include an optional Prescreening, Screening (Days -35 to -7) Phase, a 16-week Treatment Phase following randomization on Day 1. Patients will be randomly assigned in a ratio of 1:1:1:1 to receive Saroglitazar Magnesium 1mg or 2 mg or 4 mg or matching placebo once daily in the morning before breakfast for 16 Weeks. The primary endpoint of the study is percentage change from baseline in serum Alanine transaminase (ALT) levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group.

Conditions

Non-Alcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis

Keywords

NASH; NAFLD; Saroglitazar

Outcome Measures

Primary Outcomes (1)

• Percentage Change From Baseline in Serum Alanine Aminotransferase (ALT) Levels at Week 16

  Percentage change from baseline in serum ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group

  Baseline and Week 16

Secondary Outcomes (15)

• Change in Liver Fat Content as Measured by Magnetic Resonance Imaging-derived Proton Density-fat Fraction (MRI-PDFF)

  Baseline and Week 16

• Proportion of Patients With Sustain Decrease in Serum ALT Levels

  Week 16

• Changes in Cytokeratin-18

  baseline and Week 16

• Changes in Enhanced Liver Fibrosis

  baseline and Week 16

• Change in Aspartate Aminotransferase-to-platelet Ratio Index

  Baseline and Week 16

Study Arms (4)

Saroglitazar magnesium 1 mg

EXPERIMENTAL

Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks.

Drug: Saroglitazar magnesium 1 mg

Saroglitazar magnesium 2 mg

EXPERIMENTAL

Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks.

Drug: Saroglitazar magnesium 2 mg

Saroglitazar magnesium 4 mg

EXPERIMENTAL

Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks.

Drug: Saroglitazar magnesium 4 mg

Placebos

PLACEBO COMPARATOR

Placebo tablet orally once daily in the morning before breakfast for 16 weeks.

Drug: Placebos

Interventions

Saroglitazar magnesium 1 mg DRUG

Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.

Saroglitazar magnesium 1 mg

Saroglitazar magnesium 2 mg DRUG

Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.

Saroglitazar magnesium 2 mg

Saroglitazar magnesium 4 mg DRUG

Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Saroglitazar magnesium 4 mg

Placebos DRUG

Patients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks.

Placebos

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, 18 to 75 years of age, with body mass index (BMI) ≥ 25 kg/m\^2.
• Documented diagnosis of NAFLD established either by imaging (ultrasound, computed tomography \[CT\] scan or Magnetic resonance imaging \[MRI\]) or liver biopsy showing NASH or simple steatosis, within the 24 months preceding Visit 1. The diagnosis of NAFLD is made according to the American Association for the Study of Liver Diseases (AASLD) criteria (Chalasani et al. Hepatology 2012; 55:2005-2023).
• ALT level of ≥50 U/L at Visit 1 and Visit 2 with ≤30% variance between the levels at Visit 1 and Visit 2.
• Patient's demonstration of understanding of study requirements and treatment procedures, willingness to comply with all protocol-required evaluations; provision of written informed consent before any study specific tests or procedures are performed.

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 5 years preceding Visit 1 (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor).
• Presence of alternative causes of fatty liver, including:
• Weight change \>5% within the 3 months preceding Visit 1
• Total parenteral nutrition, starvation or protein-calorie malnutrition within the 90 days preceding Visit 1.
• Use of drugs associated with NAFLD for more than 12 consecutive weeks in the 1 year before Visit 1, including amiodarone, tamoxifen, methotrexate, systemic glucocorticoids, anabolic steroids, tetracycline, estrogens in doses higher than used in oral contraceptives, vitamin A, L asparaginase, valproate, chloroquine or antiretroviral drugs
• Initiation of vitamin E at doses \> 100 IU/day, or multivitamins containing \> 100 IU/day of vitamin E in the 3 months preceding Visit 1.
• Use of drugs with potential effect on NASH such as ursodeoxycholic acid, S-adenosylmethionine (SAM-e), betaine, pentoxifylline, obeticholic acid or milk thistle in the 3 months prior to Visit 1.
• Changing doses of statins (simvastatin, pitavastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, fenofibrate) in the 3 months preceding Visit 1.
• Use of thiazolidinediones (pioglitazone, rosiglitazone).
• Use of drugs that are known Cytochrome P4502C8 (CYP2C8) inhibitors/substrate
• History of bowel surgery (gastrointestinal (bariatric) surgery or undergoing evaluation for bariatric surgery for obesity, extensive small-bowel resection or orthotopic liver transplant (OLT) or listed for OLT.
• History of other chronic liver disease (chronic hepatitis C, (HCV) infection, irrespective of their mRNA HCV assay status or active hepatitis B infection, (i.e., serum positive for hepatitis B surface antigen) or autoimmune hepatitis, cholestatic and metabolic liver diseases) or hemochromatosis
• Patient has known cirrhosis, either based on clinical criteria or liver histology.
• Patient with Internation Normalised Ratio (INR) \>1.3.
• Type 1 diabetes mellitus.

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (18)

Precision Research

Chula Vista, California, 91910, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

California liver research institute

Pasadena, California, 91105, United States

Location

Precision Research

San Diego, California, 92114, United States

Location

University of Florida

Gainesville, Florida, 32601, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Avail Clinical Research

Orange City, Florida, 32763, United States

Location

Indiana University

Indianapolis, Indiana, 46290, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5362, United States

Location

Awasty Research Network, LLC

Marion, Ohio, 43302, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

AIG Research

Hermitage, Tennessee, 37076, United States

Location

Liver Consultants

Dallas, Texas, 75246, United States

Location

The Liver Institute

San Antonio, Texas, 78215, United States

Location

Swedish Medical Center

Seattle, Washington, 89104, United States

Location

Related Publications (3)

• Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.

  PMID: 22488764 BACKGROUND

• Gawrieh S, Noureddin M, Loo N, Mohseni R, Awasty V, Cusi K, Kowdley KV, Lai M, Schiff E, Parmar D, Patel P, Chalasani N. Saroglitazar, a PPAR-alpha/gamma Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial. Hepatology. 2021 Oct;74(4):1809-1824. doi: 10.1002/hep.31843. Epub 2021 Jul 19.

  PMID: 33811367 RESULT

• Siddiqui MS, Parmar D, Sheikh F, Sarin SK, Cisneros L, Gawrieh S, Momin T, Duseja A, Sanyal AJ. Saroglitazar, a Dual PPAR alpha/gamma Agonist, Improves Atherogenic Dyslipidemia in Patients With Non-Cirrhotic Nonalcoholic Fatty Liver Disease: A Pooled Analysis. Clin Gastroenterol Hepatol. 2023 Sep;21(10):2597-2605.e2. doi: 10.1016/j.cgh.2023.01.018. Epub 2023 Jan 31.

  PMID: 36731585 DERIVED

Related Links

• Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of
• Gawrieh S, Noureddin M, Loo N, Mohseni R, Awasty V, Cusi K, Kowdley KV, Lai M, Schiff E, Parmar D, Patel P, Chalasani N. Saroglitazar, a PPAR-alpha/gamma Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

saroglitazar

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

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

dparmar@zydustherapeutics.com

7324050886

Study Officials

• Deven V 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 23, 2017
• Study Start: April 6, 2017
• Primary Completion: August 22, 2019
• Study Completion: August 22, 2019
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-10

Locations

US (18)