Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Saroglitazar Magnesium in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis (EVIDENCES IV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03061721
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Zydus Discovery DMCC

Brief Summary:
This is a randomized, double-blind, placebo-controlled study in up to 104 patients with a diagnosis of NAFLD and/or 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 ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Drug: Saroglitazar magnesium 1 mg Drug: Saroglitazar magnesium 2 mg Drug: Saroglitazar magnesium 4 mg Drug: Placebos Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Prospective, Multicenter, Double-blind, Randomized Study of Saroglitazar Magnesium 1 mg, 2 mg or 4 mg Versus Placebo in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis
Actual Study Start Date : April 6, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: Saroglitazar magnesium 1 mg
Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks.
Drug: Saroglitazar magnesium 1 mg
Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.

Experimental: Saroglitazar magnesium 2 mg
Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks.
Drug: Saroglitazar magnesium 2 mg
Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.

Experimental: Saroglitazar magnesium 4 mg
Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks.
Drug: Saroglitazar magnesium 4 mg
Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Placebo Comparator: Placebos
Placebo tablet orally once daily in the morning before breakfast for 16 weeks.
Drug: Placebos
Patients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks.




Primary Outcome Measures :
  1. Percentage change from baseline in serum ALT levels at Week 16 [ Time Frame: 16 Weeks ]
    Percentage change from baseline in serum ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group


Secondary Outcome Measures :
  1. Change in liver fat content as measured by magnetic resonance imaging-derived proton density-fat fraction (MRI-PDFF) [ Time Frame: 16 Weeks ]
    Change in liver fat content as measured by magnetic resonance imaging-derived proton in Saroglitazar Magnesium groups as compared to the placebo group

  2. Proportion of patients with sustain decrease in serum ALT levels [ Time Frame: 16 Weeks ]
    Proportion of patients with sustain decrease in serum ALT levels in Saroglitazar Magnesium groups as compared to the placebo group

  3. Changes in cytokeratin-18 [ Time Frame: 16 Weeks ]
    Changes in cytokeratin-18 in Saroglitazar Magnesium groups as compared to the placebo group

  4. Changes in enhanced liver fibrosis [ Time Frame: 16 Weeks ]
    Changes in enhanced liver fibrosis in Saroglitazar Magnesium groups as compared to the placebo group

  5. Change in aspartate aminotransferase-to-platelet ratio index [ Time Frame: 16 Weeks ]
    Change in aspartate aminotransferase-to-platelet ratio index in Saroglitazar Magnesium groups as compared to the placebo group

  6. Pharmacokinetics of Saroglitazar Magnesium: maximum plasma concentration (Cmax) [ Time Frame: 16 Weeks ]
    Maximum plasma concentration (Cmax) of Saroglitazar

  7. Time to reach maximum plasma concentration (Tmax) [ Time Frame: 16 Week ]
    Time to reach maximum plasma concentration (Tmax) of saroglitazar

  8. Terminal half life (t1/2) [ Time Frame: 16 Weeks ]
    Terminal half life (t1/2) of saroglitazar

  9. Area under the curve from the time of dosing to the last measurable concentration (AUC0-t) [ Time Frame: 16 Week ]
    Area under the curve from the time of dosing to the last measurable concentration for saroglitazar

  10. Area under the curve from the time of dosing to the infinity (AUC 0-inf) [ Time Frame: 16 Week ]
    Area under the curve from the time of dosing to the infinity (AUC 0-inf) for Saroglitazar

  11. Elimination rate constant (λz) [ Time Frame: 16 Week ]
    Elimination rate constant (λz) for saroglitazar

  12. Apparent volume of distribution (Vd/F) [ Time Frame: 16 Week ]
    Apparent volume of distribution (Vd/F) for Saroglitazar

  13. Apparent clearance (CL/F) [ Time Frame: 16 Week ]
    Apparent clearance (CL/F) for Saroglitazar

  14. Change in quality of life assessed by the Short-Form 36 Health Survey [ Time Frame: 16 Week ]
    Quality of life will be assessed by the Short-Form 36 Health Survey

  15. Safety and tolerability of Saroglitazar Magnesium [ Time Frame: 16 Weeks ]
    Assessed by incidence of adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females, 18 to 75 years of age, with body mass index (BMI) ≥ 25 kg/m2.
  2. Documented diagnosis of NAFLD established either by imaging (ultrasound, CT scan or 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).
  3. ALT level of ≥50 U/L at Visit 1 and Visit 2 with ≤30% variance between the levels at Visit 1 and Visit 2.
  4. 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.

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 5 years preceding Visit 1 (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor).
  2. Presence of alternative causes of fatty liver, including:

    1. Weight change >5% within the 3 months preceding Visit 1
    2. Total parenteral nutrition, starvation or protein-calorie malnutrition within the 90 days preceding Visit 1.
    3. 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
  3. 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.
  4. 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.
  5. Changing doses of statins (simvastatin, pitavastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, fenofibrate) in the 3 months preceding Visit 1.
  6. Use of thiazolidinediones (pioglitazone, rosiglitazone).
  7. Use of drugs that are known CYP2C8 inhibitors/substrate
  8. 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.
  9. 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
  10. Patient has known cirrhosis, either based on clinical criteria or liver histology.
  11. Patient with INR >1.3.
  12. Type 1 diabetes mellitus.
  13. Poorly controlled type 2 diabetes mellitus, i.e., glycosylated hemoglobin (HbA1c) > 9%.
  14. Unstable cardiovascular disease, including:

    1. unstable angina, (i.e., new or worsening symptoms of coronary heart disease within the 3 months preceding Visit 1), acute coronary syndrome within the 6 months preceding Visit 1, acute myocardial infarction within the 3 months preceding Visit 1 or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, within the 6 months preceding Visit 1
    2. history of (within 3 months preceding Visit 1) or current unstable cardiac dysrhythmias
    3. uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg and/or diastolic BP > 100 mmHg)
    4. stroke or transient ischemic attack within the 6 months preceding Visit 1.
  15. History of myopathies or evidence of active muscle disease.
  16. History of malignancy in the 5 years preceding Visit 1 and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
  17. Any of the following laboratory values:

    1. Hemoglobin < 9 g/dL
    2. White blood cell count < 2.5 × 103/μL
    3. Neutrophil count < 1.5 × 103/μL
    4. Platelets < 100 × 103/μL
    5. Total Serum bilirubin > 1.5 mg/dL (except in patient with known Gilbert bilirubin where TB up to 2.5 mg/dL is allowed), if it is <1.5 mg/dL at screening and >30% variance in the levels at Visit 1 and Visit 2
    6. Albumin < 3.2 g/dL
    7. Serum creatinine >1.5 mg/dL
    8. Serum ALT or AST > 250 IU/L at Visit 1 or Visit 2 .
  18. Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium.
  19. Known allergy, sensitivity or intolerance to the study drug, placebo or formulation ingredients.
  20. Participation in any other therapeutic clinical study within the 3 months preceding Visit 1, including participation in any other NAFLD/NASH clinical trials.
  21. History of bladder disease and/or hematuria or has current hematuria except due to a urinary tract infection.
  22. Illicit substance abuse within the 12 months preceding Visit 1.
  23. Pregnancy-related exclusions, including:

    1. Pregnant/lactating female (including a positive serum pregnancy test at Visit 1)
    2. A male patient has to use a condom with spermicide, and the female partner of the male patient has to use an intrauterine device OR a diaphragm with spermicide OR oral contraceptive pills.
    3. If a male patient has undergone a vasectomy, the female partner does not have to use any contraception.
    4. A female patient has to use either an intrauterine device OR a diaphragm with spermicide OR oral contraceptive pills. The male partner of the female patient has to use a condom with spermicide.
    5. If the female patient is surgically sterilized for at least the 6 months preceding Visit 1 or postmenopausal, defined as at least 12 months with no menses and without an alternative cause, the male partner of the female patient does not have to use any contraception.
  24. 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, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061721


Contacts
Layout table for location contacts
Contact: Deven V Parmar, MD,FACP,FCP +971 43998280 deven.parmar@zydusdiscovery.ae
Contact: Richa P Vellanki 2717665555 ext 454 Richa.Vellanki@zyduscadila.com

Locations
Layout table for location information
United States, California
Precision Research Recruiting
Chula Vista, California, United States, 91910
Contact: Research Site         
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Research Site         
Catalina Research Institute Recruiting
Montclair, California, United States, 91763
Contact: Joe Calleros         
California liver research institute Recruiting
Pasadena, California, United States, 91105
Contact: Stephanie Tang         
Precision Research Recruiting
San Diego, California, United States, 92114
Contact: Research Site         
Medical Associates Research Group Recruiting
San Diego, California, United States, 92123
Contact: Tina Delrosa         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32601
Contact: Research Site         
Schiff Center for Liver Diseases/University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Diane Sabogal         
Avail Clinical Research Recruiting
Orange City, Florida, United States, 32763
Contact: Samantha Watts         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46290
Contact: Research Site         
United States, Maryland
Mercy Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Research Site         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-5362
Contact: Elizabeth Wu         
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Research Site         
United States, North Carolina
Wake Internal Medicine Withdrawn
Raleigh, North Carolina, United States, 27612
United States, Ohio
Awasty Research Network, LLC Recruiting
Marion, Ohio, United States, 43302
Contact: Elisia Baldwin         
United States, Pennsylvania
Einstein Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19141
Contact: Stacey J Carmody         
United States, Tennessee
Gastro One Recruiting
Germantown, Tennessee, United States, 38138
Contact: Laurie Martin         
AIG Research Recruiting
Hermitage, Tennessee, United States, 37076
Contact: Research Site         
United States, Texas
Liver Consultants Recruiting
Dallas, Texas, United States, 75246
Contact: Research Site         
The Liver Institute Recruiting
San Antonio, Texas, United States, 78215
Contact: Research Site         
United States, Washington
Swedish Medical Center Recruiting
Seattle, Washington, United States, 89104
Contact: Research Site         
Sponsors and Collaborators
Zydus Discovery DMCC
Investigators
Layout table for investigator information
Study Director: Deven V Parmar, MD,FACP,FCP Zydus Discovery DMCC

Publications:
Layout table for additonal information
Responsible Party: Zydus Discovery DMCC
ClinicalTrials.gov Identifier: NCT03061721     History of Changes
Other Study ID Numbers: SARO.16.005.03.PROT
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zydus Discovery DMCC:
NASH
NAFLD
Saroglitazar

Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases