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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non-alcoholic Fatty Liver Disease in Women With PCOS

Intervention / Treatment
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* Drug: Saroglitazar Magnesium 4 mg Tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females, 18 to 45 years of age. Previously confirmed diagnosis of PCOS: oligo-and/or anovulation; hyperandrogenism (clinical and/or biochemical); 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 MRI-PDFF | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver enzymes/LFTs | Changes from baseline to week 12 and week 24 in liver enzymes/LFTs: ALT, AST, ALP,GGT, serum protein, albumin and total bilirubin. | 12 and 24 weeks | 
| Insulin resistance | Changes from baseline to week 12 and week 24 in insulin resistance as measured by HOMA | 12 and 24 weeks | 
| Markers of liver injury | Changes from baseline to week 24 in markers of liver injury | 24 weeks | 
| Liver fibrosis | Changes from baseline to week 24 in fibrosis including CK-18, hs-CRP, and TNFα | 24 weeks | 
| Liver stiffness | Changes from baseline to week 24 in liver stiffness measured by transient elastography/FibroScan | 24 weeks | 
| Controlled attenuation parameter | Changes from baseline to week 24 in controlled attenuation parameter measured by transient elastography/ FibroScan | 24 weeks | 
| BMI | Changes from baseline to week 12 and week 24 in BMI | 12 and 24 weeks | 
| Waist circumference | Changes from baseline to week 12 and week 24 in waist circumference | 12 and 24 weeks | 
| MRI-derived measures of total liver fat index (It will be calculated as the product of liver volume and the liver mean proton-density fat fraction across all liver segments) | Changes from baseline to week 24 in MRI-derived measures of total liver fat index | 24 weeks | 
| 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]) | Changes from baseline to week 24 in MRI-derived measures of total liver volume | 24 weeks | 
| Lipid and lipoprotein levels | Changes from baseline to week 12 and week 24 in lipid and lipoprotein levels: TG, TC, HDL, LDL, sdLDL, VLDL, apolipoprotein A and apolipoprotein B | 12 and 24 weeks | 
| SHBG level | Changes from baseline to week 12 and week 24 in SHBG level | 12 and 24 weeks | 
| Ovarian function | Changes from baseline to week 12 and week 24 in ovarian function (Total testosterone, 17-hydroxyprogesterone, free testosterone, luteinizing hormone, follicle-stimulating hormone, LH-to-FSH ratio and estradiol) | 12 and 24 weeks | 
| Free androgen index ( Total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by a constant, usually 100. The concentrations of testosterone and SHBG are normally measured in nanomols per liter. | Changes from baseline to week 12 and week 24 in free androgen index | 12 and 24 weeks | 
| Peak Plasma concentration [Cmax] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Time to reach peak Plasma concentration [Tmax] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Area under Plasma concentration vs. time curve till the last time point [AUC0-t] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Area under Plasma concentration vs. time curve extrapolated to the infinity (AUC0-∞) after first dose (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| 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 | 24 weeks | 
| Elimination rate constant [Kel] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Elimination half-life [tHalf] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Apparent Volume of distribution [Vd/F] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Apparent Clearance [CL/F] (For Single Dose) | Pharmacokinetics of Saroglitazar following first dose | 24 weeks | 
| Peak Plasma concentration [Cmax,ss] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Time to reach peak Plasma concentration [Tmax,ss] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| 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 | 24 weeks | 
| Elimination rate constant [Kel,ss] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Elimination half-life [thalf,ss] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Apparent Volume of distribution [Vd/F,ss] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Apparent Clearance [CL/F,ss] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Minimal or Trough plasma concentration [Cmin] (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Fluctuation index (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 
| Accumulation index calculated as a ratio of AUCtau (last dose)/AUCtau (first dose) (For Multiple Dose) | Pharmacokinetics of Saroglitazar following last dose | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, PCOS, Saroglitazar Magnesium