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)

Zydus Therapeutics Inc.19 sites in 2 countries90 target enrollmentFebruary 12, 2019

InterventionsSaroglitazar Magnesium 4 mg Tablet Placebo

Overview

Phase: Phase 2
Intervention: Saroglitazar Magnesium 4 mg Tablet
Conditions: Not specified
Sponsor: Zydus Therapeutics Inc.
Enrollment: 90
Locations: 19
Primary Endpoint: Hepatic Fat Content
Status: Terminated
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

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.

Registry

clinicaltrials.gov

Start Date

February 12, 2019

End Date

October 28, 2024

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Zydus Therapeutics Inc.

Responsible Party

Sponsor

Eligibility Criteria

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
•Visit 2 ALT must not increase \>30% from Visit
•Hepatic fat fraction ≥10% by MRI-PDFF.
•Willingness to participate in the study.

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.

Arms & Interventions

Saroglitazar Magnesium 4 mg

Saroglitazar Magnesium once daily in the morning before breakfast

Intervention: Saroglitazar Magnesium 4 mg Tablet

Placebo

Placebo tablet once daily in the morning before breakfast

Intervention: Placebo

Outcomes

Primary Outcomes

Hepatic Fat Content

Time Frame: Baseline and Week 24

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)

Secondary Outcomes

Time to Reach Peak Plasma Concentration [Tmax] (For Single 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)(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,ss] (For Multiple 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))
Liver Enzymes/Liver Function Tests(Baseline, Week 12, and Week 24)
Insulin Resistance(Baseline, Week 12, and Week 24)
Liver Injury(Baseline and Week 24)
Liver Stiffness(Baseline and Week 24)
Controlled Attenuation Parameter(Baseline and Week 24)
Body Mass Index (BMI)(Baseline, Week 12, and Week 24)
Waist Circumference(Baseline, Week 12, and Week 24)
Apparent Volume of Distribution [Vd/F,ss] (For Multiple 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))
Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Fat Index(Baseline and Week 24)
Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Volume(Baseline and Week 24)
Lipid and Lipoprotein Levels(Baseline, Week 12, and Week 24)
Sex Hormone Binding Globulin (SHBG) Level(Baseline, Week 12, and Week 24)
Ovarian Function(Baseline, Week 12, and Week 24)
Changes From Baseline to Week 12 and Week 24 in Free Androgen Index(Baseline, Week 12, and Week 24)
Peak Plasma Concentration [Cmax] (For Single 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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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))