Saroglitazar Magnesium in Patients With Nonalcoholic Fatt... | NCT03061721

NCT03061721

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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	Baseline and Week 16
Proportion of Patients With Sustain Decrease in Serum ALT Levels

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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:
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
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.
Poorly controlled type 2 diabetes mellitus, i.e., glycosylated hemoglobin (HbA1c) > 9%.
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.
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:
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 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
6. Albumin < 3.2 g/dL
7. Serum creatinine >1.5 mg/dL
8. 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:
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.
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).

Contacts/Locations Module

Name	Affiliation	Role
Deven V Parmar, MD,FACP,FCP	Zydus Therapeutics Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Precision Research		Chula Vista	California	91910	United States
Cedars-Sinai Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22488764	Background	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.
33811367

Label	URL
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	View source

ID	Title	Description
FG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 26, 2018	Dec 23, 2023

Categories

Title	Measurements
	BG00051.1± 12.89 BG00147.9± 10.44 BG00249± 10.97 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00013 BG00112 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00010 BG0018 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

Body Mass Index

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00033.630± 4.2451 BG00135.702± 8.5653 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Full Analysis Set

Posted

Mean

Standard Deviation

Percentage change

Baseline and Week 16

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.
OG003	Placebo	Placebo tablet orally once daily in the morning before breakfast for 16 weeks.

Units	Counts
Participants	OG00026 OG00125 OG00227 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-26.2± 33.36 OG001-27.0± 26.52 OG002-44.9± 26.26 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003		ANCOVA		0.0002														Superiority
OG001 OG003		ANCOVA		0.0001

Secondary

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

Full analysis set

Posted

Mean

Standard Deviation

percentage of Liver fat

Baseline and Week 16

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

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

Full Analysis set

Posted

Count of Participants

Participants

Week 16

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

Changes in Cytokeratin-18

Changes in cytokeratin-18 in Saroglitazar Magnesium groups as compared to the placebo group

full analysis set

Posted

Mean

Standard Deviation

U/L

baseline and Week 16

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.
OG003

Secondary

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

Full Analysis Set

Posted

Mean

Standard Deviation

units on a scale

baseline and Week 16

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.

Secondary

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

Full Analysis set

Posted

Mean

Standard Deviation

units on a scale

Baseline and Week 16

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg

Secondary

Pharmacokinetics of Saroglitazar Magnesium: Maximum Plasma Concentration (Cmax)

Maximum plasma concentration (Cmax) of Saroglitazar

PK population

Posted

Mean

Standard Deviation

ng/mL

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

Time to Reach Maximum Plasma Concentration (Tmax)

Time to reach maximum plasma concentration (Tmax) of saroglitazar

PK population

Posted

Median

Full Range

hours

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

Terminal Half-life (t1/2)

Terminal Half-life (t1/2) of saroglitazar

PK population For Saroglitazar 4 mg, one subject was not considered for calculation of Half-life as adjusted R square was observed <0.8000 and AUC_%Extrap_obs>20%. Hence, N=07 instead of 08 for Half-life

Posted

Mean

Standard Deviation

hour

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

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

PK population

Posted

Mean

Standard Deviation

hr*ng/mL

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

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

PK population For Saroglitazar 4 mg, one subject was not considered for calculation of AUC 0-inf as adjusted R square was observed <0.8000 and AUC_%Extrap_obs>20%. Hence, N=07 instead of 08 for AUC 0-inf

Posted

Mean

Standard Deviation

hr*ng/mL

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

Elimination Rate Constant (λz)

Elimination rate constant (λz) for saroglitazar

PK population For Saroglitazar 4 mg, one subject was not considered for calculation of Kel as adjusted R square was observed <0.8000 and AUC_%Extrap_obs>20%. Hence, N=07 instead of 08 for Kel

Posted

Mean

Standard Deviation

per hour

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

Apparent Volume of Distribution (Vd/F)

Apparent volume of distribution (Vd/F) for Saroglitazar

PK population For Saroglitazar 4 mg, one subject was not considered for calculation of Vd/F as adjusted R square was observed <0.8000 and AUC_%Extrap_obs>20%. Hence, N=07 instead of 08 for Vd/F

Posted

Mean

Standard Deviation

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

Apparent Clearance (CL/F)

Apparent clearance (CL/F) for Saroglitazar

PK population For Saroglitazar 4 mg, one subject was not considered for calculation of CL/F as adjusted R square was observed <0.8000 and AUC_%Extrap_obs>20%. Hence, N=07 instead of 08 for CL/F.

Posted

Mean

Standard Deviation

mL/hour

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)

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.

Secondary

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.

Full Analysis Set

Posted

Mean

Standard Deviation

units on a scale

baseline and 16 Week

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.

Secondary

Safety and Tolerability of Saroglitazar Magnesium

Number of participants with adverse events

Safety Analysis Set

Posted

Number

participants

Baseline to Week 17

ID	Title	Description
OG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
OG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
OG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.
OG003

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.	26	1	26	7	26
EG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.	25	0	25	6	25
EG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.	27	1	27	3	27
EG003	Placebos	Placebo tablet orally once daily in the morning before breakfast for 16 weeks. Placebos: Patients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks.	28	0	28	5	28

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Ureterolithiasis	Renal and urinary disorders		Systematic Assessment		EG0001 affected26 at risk EG0010 affected25 at risk EG0020 affected27 at risk EG0030 affected28 at risk
Mental Status Change	Psychiatric disorders		Systematic Assessment		EG0000 affected26 at risk EG0010 affected25 at risk EG0021 affected27 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected26 at risk EG0012 affected25 at risk EG0020 affected27 at risk EG0030 affected28 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected26 at risk EG0011 affected25 at risk EG0020 affected27 at risk EG003
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected26 at risk EG0012 affected25 at risk EG0020 affected27 at risk EG003
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 affected26 at risk EG0012 affected25 at risk EG0022 affected27 at risk EG003
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 affected26 at risk EG0010 affected25 at risk EG0021 affected27 at risk EG003
Headache	Nervous system disorders	Systematic Assessment	EG0003 affected26 at risk EG0011 affected25 at risk EG0021 affected27 at risk EG003
Haematuria	Renal and urinary disorders	Systematic Assessment	EG0001 affected26 at risk EG0010 affected25 at risk EG0021 affected27 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected26 at risk EG0010 affected25 at risk EG0021 affected27 at risk EG003
Flatulence	Gastrointestinal disorders	Systematic Assessment	EG0000 affected26 at risk EG0010 affected25 at risk EG0020 affected27 at risk EG003

First MCP Posted Date

ID	Term
D065626	Non-alcoholic Fatty Liver Disease

ID	Term
C000588741	saroglitazar

BG00333.809± 4.4599

BG00433.875± 5.8374

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

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

ID	Title	Description
BG000	Saroglitazar Magnesium 1 mg	Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 1 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
BG001	Saroglitazar Magnesium 2 mg	Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 2 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
BG002	Saroglitazar Magnesium 4 mg	Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks. Saroglitazar magnesium 4 mg: Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.
BG003	Placebos	Placebo tablet orally once daily in the morning before breakfast for 16 weeks. Placebos: Patients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks.
BG004	Total	Total of all reporting groups

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases