Non-Alcoholic Fatty Liver DiseasePhase 2EVIDENCES IVNCT03061721
Saroglitazar Magnesium in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis
A Phase 2 study testing Saroglitazar magnesium 1 mg, Saroglitazar magnesium 2 mg and Saroglitazar magnesium 4 mg in people with Non-Alcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by Zydus Therapeutics Inc. at 18 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis
- What is being tested?
- Saroglitazar magnesium 1 mg, Saroglitazar magnesium 2 mg and Saroglitazar magnesium 4 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 18 sitesUnited States
- Study dates
- 6 Apr 2017to 22 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 44Show fewer
- 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.
- Poorly controlled type 2 diabetes mellitus, i.e., glycosylated hemoglobin (HbA1c) > 9%.
- Unstable cardiovascular disease, including:
- 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
- history of (within 3 months preceding Visit 1) 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 6 months preceding Visit 1.
- History of myopathies or evidence of active muscle disease.
- History of malignancy in the 5 years preceding Visit 1 and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
- Any of the following laboratory values:
- Hemoglobin < 9 g/dL
- White blood cell count < 2.5 × 103/μL
- Neutrophil count < 1.5 × 103/μL
- Platelets < 100 × 103/μL
- Total Serum bilirubin > 1.5 mg/dL (except in patient with known Gilbert bilirubin where Total Bilirubin 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
- Albumin < 3.2 g/dL
- Serum creatinine >1.5 mg/dL
- Serum ALT or Aspartate aminotransferase (AST) > 250 IU/L at Visit 1 or Visit 2 .
- Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium.
- Known allergy, sensitivity or intolerance to the study drug, placebo or formulation ingredients.
- Participation in any other therapeutic clinical study within the 3 months preceding Visit 1, including participation in any other NAFLD/NASH clinical trials.
- History of bladder disease and/or hematuria or has current hematuria except due to a urinary tract infection.
- Illicit substance abuse within the 12 months preceding Visit 1.
- Pregnancy-related exclusions, including:
- Pregnant/lactating female (including a positive serum pregnancy test at Visit 1)
- 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.
- If a male patient has undergone a vasectomy, the female partner does not have to use any contraception.
- 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.
- 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.
- 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).
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
University of Michigan
Ann Arbor, Michigan, 48109-5362
Mercy Medical Center
Baltimore, Maryland, 21201
Precision Research
Chula Vista, California, 91910
Liver Consultants
Dallas, Texas, 75246
University of Florida
Gainesville, Florida, 32601
Gastro One
Germantown, Tennessee, 38138
AIG Research
Hermitage, Tennessee, 37076
Indiana University
Indianapolis, Indiana, 46290
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Awasty Research Network, LLC
Marion, Ohio, 43302
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, 33136
Catalina Research Institute
Montclair, California, 91763
Avail Clinical Research
Orange City, Florida, 32763
California liver research institute
Pasadena, California, 91105
Einstein Medical Center
Philadelphia, Pennsylvania, 19141
The Liver Institute
San Antonio, Texas, 78215
Precision Research
San Diego, California, 92114
Swedish Medical Center
Seattle, Washington, 89104
About this study
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
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.
- Being tested
- Saroglitazar magnesium 1 mg, Saroglitazar magnesium 2 mg, Saroglitazar magnesium 4 mg, Placebos
- Keywords
- NASH, NAFLD, Saroglitazar
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saroglitazar magnesium 1 mgDrug
Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
Saroglitazar magnesium 2 mgDrug
Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
Saroglitazar magnesium 4 mgDrug
Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.
PlacebosDrug
Patients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Saroglitazar magnesium 1 mg | Experimental | Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Receives: 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. Receives: 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. Receives: Drug: Saroglitazar magnesium 4 mg |
| Placebos | Placebo comparator | Placebo tablet orally once daily in the morning before breakfast for 16 weeks. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Change in liver fat content as measured by magnetic resonance imaging-derived proton in Saroglitazar Magnesium groups as compared to the placebo group
Measured: Baseline and Week 16
Proportion of Patients With Sustain Decrease in Serum ALT Levels
Proportion of patients with sustain decrease in serum ALT levels in Saroglitazar Magnesium groups as compared to the placebo group
Measured: Week 16
Changes in Cytokeratin-18
Changes in cytokeratin-18 in Saroglitazar Magnesium groups as compared to the placebo group
Measured: baseline and Week 16
Changes in Enhanced Liver Fibrosis
Changes in enhanced liver fibrosis in Saroglitazar Magnesium groups as compared to the placebo group The ELF Score is a liver fibrosis score that is calculated by use of an algorithm: ELF score score = -7.412 + (ln(HA)*0.681) + (ln(P3NP)*0.775) + (ln(TIMP1)*0.494).
HA=hyaluronic acid concentration P3NP=procollagen 3 amino terminal peptide concentration TIMP1=tissue inhibitor matrix metalloproteinase 1 concentration. All are measured in serum.
The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. The ELF score is hence used as a prognostic marker for disease progression: ELF score < 9.8 : Low risk of progression, ELF score 9.8 to < 11.3 : Moderate risk of progression and ELF score > = 11.3 : High risk of progression
Measured: baseline and Week 16
Change in Aspartate Aminotransferase-to-platelet Ratio Index
Change in aspartate aminotransferase-to-platelet ratio index in Saroglitazar Magnesium groups as compared to the placebo group APRI was calculated as ([AST level/AST upper limit of normal]/ [Platelet count 1^09/L]) ×100, where AST is aspartate aminotransferase. The aspartate transaminase to platelet ratio index (APRI) is used to assess the risk of liver fibrosis.
Higher APRI score represents a higher risk of liver fibrosis
Measured: Baseline and Week 16
Pharmacokinetics of Saroglitazar Magnesium: Maximum Plasma Concentration (Cmax)
Maximum plasma concentration (Cmax) of Saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Time to Reach Maximum Plasma Concentration (Tmax)
Time to reach maximum plasma concentration (Tmax) of saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Terminal Half-life (t1/2)
Terminal Half-life (t1/2) of saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-t)
Area under the curve from the time of dosing to the last measurable concentration for saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 3 (Week 0)
Area Under the Curve From the Time of Dosing to the Infinity (AUC 0-inf)
Area under the curve from the time of dosing to the infinity (AUC 0-inf) for Saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 3 (Week 0)
Elimination Rate Constant (λz)
Elimination rate constant (λz) for saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Apparent Volume of Distribution (Vd/F)
Apparent volume of distribution (Vd/F) for Saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Apparent Clearance (CL/F)
Apparent clearance (CL/F) for Saroglitazar
Measured: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Change in Quality of Life Assessed by the Short-Form 36 Health Survey
Quality of life will be assessed by the Short-Form 36 Health Survey The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
Measured: baseline and 16 Week
Safety and Tolerability of Saroglitazar Magnesium
Number of participants with adverse events
Measured: Baseline to Week 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start6 Apr 2017
- Primary completion22 Aug 2019
- Study completion22 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zydus Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Deven V Parmar, MD,FACP,FCP, Study director, Zydus Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03061721
- Sponsor's protocol ID
- SARO.16.005
- Acronym
- EVIDENCES IV
- Status last verified
- Oct 2024
- First submitted
- 7 Feb 2017
- Last updated
- 24 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 22488764Gawrieh 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.
PubMed 33811367Siddiqui 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.
PubMed 36731585
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03061721
- Acronym / sponsor ID
- EVIDENCES IV / SARO.16.005
- Keywords
- NASH, NAFLD, Saroglitazar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Zydus Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Apr 2017 (actual)
- Primary completion
- 22 Aug 2019 (actual)
- Study completion
- 22 Aug 2019 (actual)
- First posted
- 23 Feb 2017 (actual)
- Results
- Posted 24 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Saroglitazar magnesium 1 mg | Experimental | Drug: Saroglitazar magnesium 1 mgSaroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. |
| Saroglitazar magnesium 2 mg | Experimental | Drug: Saroglitazar magnesium 2 mgSaroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. |
| Saroglitazar magnesium 4 mg | Experimental | Drug: Saroglitazar magnesium 4 mgSaroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. |
| Placebos | Placebo comparator | Drug: PlacebosPlacebo tablet orally once daily in the morning before breakfast for 16 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (44 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saroglitazar magnesium 1 mgPatients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks. | Drug | Saroglitazar magnesium 1 mg |
| Saroglitazar magnesium 2 mgPatients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks. | Drug | Saroglitazar magnesium 2 mg |
| Saroglitazar magnesium 4 mgPatients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks. | Drug | Saroglitazar magnesium 4 mg |
| PlacebosPatients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks. | Drug | Placebos |
Primary outcome
Percentage Change From Baseline in Serum Alanine Aminotransferase (ALT) Levels at Week 16
Time frame: Baseline and Week 16
Percentage change from baseline in serum ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group
15 secondary outcomes
Change in Liver Fat Content as Measured by Magnetic Resonance Imaging-derived Proton Density-fat Fraction (MRI-PDFF)
Time frame: Baseline and Week 16
Proportion of Patients With Sustain Decrease in Serum ALT Levels
Time frame: Week 16
Changes in Cytokeratin-18
Time frame: baseline and Week 16
Changes in Enhanced Liver Fibrosis
Time frame: baseline and Week 16
Change in Aspartate Aminotransferase-to-platelet Ratio Index
Time frame: Baseline and Week 16
Pharmacokinetics of Saroglitazar Magnesium: Maximum Plasma Concentration (Cmax)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Terminal Half-life (t1/2)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-t)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 3 (Week 0)
Area Under the Curve From the Time of Dosing to the Infinity (AUC 0-inf)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 3 (Week 0)
Elimination Rate Constant (λz)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Apparent Volume of Distribution (Vd/F)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Apparent Clearance (CL/F)
Time frame: PK sampling timepoints: Pre-dose (0.0), 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, and 24 hours post-dose of Visit 7 (Week 16)
Change in Quality of Life Assessed by the Short-Form 36 Health Survey
Time frame: baseline and 16 Week
Safety and Tolerability of Saroglitazar Magnesium
Time frame: Baseline to Week 17
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22488764Chalasani 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.
- Results publication: PubMed 33811367Gawrieh 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.
- Derived from this study: PubMed 36731585Siddiqui 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.
- 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 ofLink provided by the sponsor.
- 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.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deven V Parmar, MD,FACP,FCP study director
Zydus Therapeutics Inc.
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Saroglitazar magnesium 1 mg, Saroglitazar magnesium 2 mg and Saroglitazar magnesium 4 mg in people with Non-Alcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by Zydus Therapeutics Inc. at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change From Baseline in Serum Alanine Aminotransferase (ALT) Levels at Week 16 (time frame: Baseline and Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03061721, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2024.