Saroglitazar Magnesium 4 mg in the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in Women With PCOS (EVIDENCES VII)

Phase 2A, Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Saroglitazar Mg 4 mg Tablet Vs Placebo for Treating Nonalcoholic Fatty Liver Disease (NAFLD) in Women With Polycystic Ovary Syndrome (PCOS)

This is a multicenter, phase 2A, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of Saroglitazar Magnesium in women with well characterized PCOS.

Study Overview

• Status: Terminated
• Conditions: Non-alcoholic Fatty Liver Disease in Women With PCOS
• Intervention / Treatment: Drug: Saroglitazar Magnesium 4 mg Tablet; Drug: Placebo

Detailed Description

This is a multicenter, phase 2A, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of Saroglitazar Magnesium in women with well characterized PCOS.

The study will be conducted over a period of up to 34 weeks and will include Screening (Days -28 to -7) Phase, a 24-week Treatment Phase following randomization on Day 1.

The primary endpoint of the study is change in hepatic fat content from baseline following 24 weeks of treatment as measured by MRI-PDFF.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 06100
    • Zydus MX003
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Zydus MX006
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Zydus MX001
    • Monterrey, Nuevo León, Mexico, 64460
      • Zydus MX002
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80230
      • Zydus MX005
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Zydus MX004
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Zydus US005
  • California
    • Panorama City, California, United States, 91402
      • Zydus US004
    • San Francisco, California, United States, 94143
      • Zydus US002
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Zydus US008
  • Florida
    • Miami, Florida, United States, 33125
      • Zydus US010
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Zydus US001
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Zydus US011
  • Ohio
    • Marion, Ohio, United States, 43302
      • Zydus US003
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Zydus US015
    • Philadelphia, Pennsylvania, United States, 19104
      • Zydus US014
  • Texas
    • Austin, Texas, United States, 78745
      • Zydus US013
    • San Antonio, Texas, United States, 78215
      • Zydus US007
    • San Antonio, Texas, United States, 78229
      • Zydus US009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females, 18 to 45 years of age.

• Previously confirmed diagnosis of PCOS:

  1. oligo-and/or anovulation;
  2. hyperandrogenism (clinical and/or biochemical);
  3. polycystic ovary morphology on ultrasonography
• Evidence of NAFLD within 6 months prior to the Screening Visit (Visit 1).
• Alanine transaminase ≥ 38 U/L at Visit 1. Visit 2 ALT must not increase >30% from Visit 1.
• Hepatic fat fraction ≥10% by MRI-PDFF.
• Willingness to participate in the study.
• Ability to understand and give informed consent for participation.
• Woman who agrees to use the contraceptive methods.

Exclusion Criteria:

• Presence of other chronic liver diseases (hepatitis B or C, autoimmune hepatitis, cholestatic liver disease, Wilsons disease, hemochromatosis, etc.).
• Average alcohol consumption ≥ 7 drinks per week for women in the 6 months prior to enrollment.
• Clinical, imaging, or histological evidence of cirrhosis.
• Patients who have used medications known to cause hepatic steatosis for more than 2 weeks in the past year.
• Prior bariatric surgery.
• Weight loss of more than 5% in the 3 months preceding screening.
• Severe co-morbidities (e.g., advanced cardiac, renal, pulmonary, or psychiatric illness).
• Known allergy, sensitivity or intolerance to Saroglitazar Magnesium, comparator or formulation ingredients.
• Use of antidiabetic and lipid lowering medications if the dose is not stable for at least the 3 months preceding screening.
• Intake of Vitamin E (>100 IU/day) or multivitamins containing Vitamin E (>100 IU/day) 3 months before enrollment.
• Use of drugs with potential effect on NAFLD/NASH in the 3 months prior to screening.
• Illicit substance abuse within the past 12 months.
• Pregnant or breast feeding females.
• Women with known Cushing syndrome or hyperprolactinemia.
• Refusal or inability to comply with the requirements of the protocol, for any reason, including scheduled clinic visits and laboratory tests.
• History of myopathies or evidence of active muscle diseases.
• History or current significant cardiovascular disease.
• History of malignancy.
• History of bladder disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saroglitazar Magnesium 4 mg; Saroglitazar Magnesium once daily in the morning before breakfast	Drug: Saroglitazar Magnesium 4 mg Tablet; Patients randomly assigned to this group will receive Saroglitazar Magnesium orally once daily for 24 weeks.; Other Names: Not any
Placebo Comparator: Placebo; Placebo tablet once daily in the morning before breakfast	Drug: Placebo; Patients randomly assigned to this group will receive Placebo tablet orally once daily for 24 weeks.; Other Names: Not any

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic Fat Content	Change in hepatic fat content from baseline following 24 weeks of treatment as measured by Magnetic Resonance Imaging-derived Proton Density-fat Fraction (MRI-PDFF)	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in Alkaline phosphatase	Baseline, Week 12, and Week 24
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in Alanine aminotransferase	Baseline, Week 12, and Week 24
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in Aspartate Aminotransferase	Baseline, Week 12, and Week 24
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in gamma-glutamyl transferase	Baseline, Week 12, and Week 24
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in serum protein	Baseline, Week 12, and Week 24
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in albumin	Baseline, Week 12, and Week 24
Liver Enzymes/Liver Function Tests	Changes from baseline to week 12 and week 24 in total bilirubin.	Baseline, Week 12, and Week 24
Insulin Resistance	Evaluation of HOMA of Insulin Resistance Index determines insulin resistance and estimates insulin sensitivity, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance	Baseline, Week 12, and Week 24
Liver Injury	Changes from baseline to week 24 in Liver Injury, including Cytokeratin (CK)-18. CK18 [M30] and CK-18 [M-65] were measured as biomarkers of hepatocyte apoptosis. Both are important indicators for liver tissue conditions and effectively reflect hepatocyte damage. A negative change from baseline indicates a decrease in hepatocyte apoptosis or a decrease in hepatocyte damage.	Baseline and Week 24
Liver Injury	Changes from baseline to week 24 in high-sensitivity C-reactive protein (hs-CRP)	Baseline and Week 24
Liver Injury	Changes from baseline to week 24 in Tumor necrosis factor (TNFα)	Baseline and Week 24
Liver Stiffness	Changes from baseline to week 24 in liver stiffness measured by transient elastography/FibroScan	Baseline and Week 24
Controlled Attenuation Parameter	Changes from baseline to week 24 in controlled attenuation parameter measured by transient elastography/ FibroScan	Baseline and Week 24
Body Mass Index (BMI)	Changes from baseline to week 12 and week 24 in Body mass index	Baseline, Week 12, and Week 24
Waist Circumference	Changes from baseline to week 12 and week 24 in waist circumference	Baseline, Week 12, and Week 24
Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Fat Index	MRI-derived measures of total liver fat index. Total liver volume: The total liver volume was calculated through a process requiring segmentation image analysis. Liver volume was calculated after complete segmentation by summing the liver surface area at each segmented slice and then multiplying this sum by individual slice thickness, in milliliters (mL). Total liver fat index: The total liver fat index (TLFI, units: % mL) took into consideration the volume of liver from which proton-density fat fraction was derived. It was calculated as the product of liver volume and the liver mean proton-density fat fraction across all liver segments.	Baseline and Week 24
Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Volume	MRI-derived measures of total liver volume (Liver volume will be calculated after complete segmentation by summing the liver surface area at each segmented slice, and then multiplying this sum by individual slice thickness, in millilitres [mL])	Baseline and Week 24
Lipid and Lipoprotein Levels	Changes from baseline to week 12 and week 24 in Triglyceride (TG)	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline to week 12 and week 24 in Total cholesterol (TC)	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline to week 12 and week 24 in High-density lipoprotein	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline to week 12 and week 24 in Low-density lipoprotein (LDL)	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline to week 12 and week 24 in Small dense low density lipoprotein (sdLDL)	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline to week 12 and week 24 in Very low density lipoprotein (VLDL)	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline apolipoprotein A	Baseline, Week 12, and Week 24
Lipid and Lipoprotein Levels	Changes from baseline in apolipoprotein B	Baseline, Week 12, and Week 24
Sex Hormone Binding Globulin (SHBG) Level	Changes from baseline in SHBG level	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in 17-hydroxyprogesterone	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in Total testosterone	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in free testosterone	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in follicle-stimulating hormone (FSH)	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in luteinizing hormone (LH)	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in LH-to-FSH ratio	Baseline, Week 12, and Week 24
Ovarian Function	Changes from baseline in estradiol	Baseline, Week 12, and Week 24
Changes From Baseline to Week 12 and Week 24 in Free Androgen Index	Free androgen index is a ratio used to determine abnormal androgen status in humans, measured by Total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by a constant, usually 100. A higher score indicates a worse outcome (more androgenic).	Baseline, Week 12, and Week 24
Peak Plasma Concentration [Cmax] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Time to Reach Peak Plasma Concentration [Tmax] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Area Under Plasma Concentration vs. Time Curve Till the Last Time Point [AUC0-t] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Area Under Plasma Concentration vs. Time Curve Extrapolated to the Infinity (AUC0-∞) After First Dose (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Area Under Plasma Concentration vs. Time Curve in a 24 h Dosing Interval (AUCtau) After First Dose (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Elimination Rate Constant [Kel] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Elimination Half-life [tHalf] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (Visit 3)
Apparent Volume of Distribution [Vd/F] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Apparent Clearance [CL/F] (For Single Dose)	Pharmacokinetics of Saroglitazar following first dose	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 First dose (visit 3)
Peak Plasma Concentration [Cmax,ss] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (Visit 8)
Time to Reach Peak Plasma Concentration [Tmax,ss] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)
Area Under Plasma Concentration vs. Time Curve in a 24 h Dosing Interval (AUCtau) After Last Dose (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)
Elimination Rate Constant [Kel,ss] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (Visit 8)
Elimination Half-life [Thalf,ss] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)
Apparent Volume of Distribution [Vd/F,ss] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)
Apparent Clearance [CL/F,ss] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)
Minimal or Trough Plasma Concentration [Cmin] (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)
Fluctuation Index (For Multiple Dose)	Pharmacokinetics of Saroglitazar following the last dose. It is calculated as (Cmax - Cmin) / Cavg. The value has been multiplied by 100, hence has been expressed in percentage unit; where Cmax is the Maximum measured plasma concentration at steady state, Cmin is Minimal or trough plasma concentration at steady state, and Cavg is Average concentration = AUCtau,ss /tau.	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 Last dose (visit 8)
Accumulation Index Calculated as a Ratio of AUCtau (Last Dose)/AUCtau (First Dose) (For Multiple Dose)	Pharmacokinetics of Saroglitazar following last dose	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 Last dose (visit 8)

Collaborators and Investigators

• Sponsor: Zydus Therapeutics Inc.
• Investigators: Study Director: Deven Parmar, MD, Zydus Therapeutics Inc.

Publications and helpful links

General Publications

• Kelley CE, Brown AJ, Diehl AM, Setji TL. Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol. 2014 Oct 21;20(39):14172-84. doi: 10.3748/wjg.v20.i39.14172.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Actual): October 28, 2024
• Study Completion (Actual): October 28, 2024

Study Registration Dates

• First Submitted: July 23, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: PCOS; NAFLD; Saroglitazar Magnesium
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Pharmaceutical Preparations; Dosage Forms; Tablets; saroglitazar
• Other Study ID Numbers: SARO.17.009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No