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

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)

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: Recruiting
• 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 (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Farheen Shaikh; Phone Number: +1 6094534751; Email: fshaikh@zydustherapeutics.com

Study Locations

• Mexico
  • Ciudad de mexico, Mexico, 06100
    • Active, not recruiting
    • CEMDEC S.A. de C.V. (Centero Mexicana Desarrollo de Estudios Clinicos)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Active, not recruiting
      • Centro de Investigación Medico Biológica y Terapia Avanzada SC (CIMBYTA)
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Active, not recruiting
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
    • Monterrey, Nuevo León, Mexico, 64460
      • Active, not recruiting
      • UBAM Unidad Biomédica Avanzada Monterrey
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80230
      • Active, not recruiting
      • Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Active, not recruiting
      • Medical Care and Research S.A. de C.V.
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Dr.Anita Kohli
      • Contact: Mari Johnson; Email: johnsonmari87@gmail.com
  • California
    • Panorama City, California, United States, 91402
      • Recruiting
      • Dr.Robert Allen Jenders
      • Contact: Vanessa Delgado; Phone Number: 3109 818-532-6880; Email: vanessa.delgado@nritrials.com
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Yanin T Srisengfa; Phone Number: 415-502-3725; Email: yanin.srisengfa@ucsf.edu
      • Contact: Rayshawnda Davis; Phone Number: 415-502-3725; Email: rayshawnda.davis@ucsf.edu
      • Principal Investigator: Dr. Monika Sarkar
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Dr.Melanie Cree Green
      • Contact: Wesley Pendleton, MS, RDN; Phone Number: 720-777-5974; Email: Wesley.Pendleton@childrenscolorado.org
      • Contact: Nicola Haakonsen; Email: NICOLA.HAAKONSEN@CUANSCHUTZ.EDU
  • Florida
    • Miami, Florida, United States, 33125
      • Recruiting
      • Dr. Yaneicy Gonzalez Rojas
      • Contact: Laylien Souza; Phone Number: 305-702-0024; Email: souza@optimusu.com
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Health
      • Contact: Regina Weber; Phone Number: 317-278-6266; Email: reginaw@iu.edu
      • Principal Investigator: Dr. Niharika Samala
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Recruiting
      • Dr. KATHRYN JEAN LUCAS
      • Contact: Ashley Bissette, BSC; Email: ashley.bissette@lucasresearch.org
  • Texas
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • Dr. Nicole Loo
      • Contact: Bertha Buan; Phone Number: 210-253-3426; Email: bbuan@txliver.com
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Dr. Mark Kipnes
      • Contact: Josette Negrete; Phone Number: 1515 210-614-8612; Email: josette.negrete@dgdclinic.com

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 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

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): December 4, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): July 1, 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): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

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
• 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