Saroglitazar Magnesium 4 mg in the Treatment of NAFLD in Women With PCOS (EVIDENCES VII)
- Conditions
- Non-alcoholic Fatty Liver Disease in Women With PCOS
- Interventions
- Drug: Placebo
- Registration Number
- NCT03617263
- Lead Sponsor
- Zydus Therapeutics Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 90
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo tablet once daily in the morning before breakfast Saroglitazar Magnesium 4 mg Saroglitazar Magnesium 4 mg Tablet Saroglitazar Magnesium once daily in the morning before breakfast
- Primary Outcome Measures
Name Time Method Hepatic fat content 24 weeks Change in hepatic fat content from baseline following 24 weeks of treatment as measured by MRI-PDFF
- Secondary Outcome Measures
Name Time Method Insulin resistance 12 and 24 weeks Changes from baseline to week 12 and week 24 in insulin resistance as measured by HOMA
Liver fibrosis 24 weeks Changes from baseline to week 24 in fibrosis including CK-18, hs-CRP, and TNFα
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) 24 weeks Changes from baseline to week 24 in MRI-derived measures of total liver fat index
Area under Plasma concentration vs. time curve extrapolated to the infinity (AUC0-∞) after first dose (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Apparent Clearance [CL/F,ss] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Minimal or Trough plasma concentration [Cmin] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Fluctuation index (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Liver enzymes/LFTs 12 and 24 weeks Changes from baseline to week 12 and week 24 in liver enzymes/LFTs: ALT, AST, ALP,GGT, serum protein, albumin and total bilirubin.
Liver stiffness 24 weeks Changes from baseline to week 24 in liver stiffness measured by transient elastography/FibroScan
Waist circumference 12 and 24 weeks Changes from baseline to week 12 and week 24 in waist circumference
SHBG level 12 and 24 weeks Changes from baseline to week 12 and week 24 in SHBG level
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. 12 and 24 weeks Changes from baseline to week 12 and week 24 in free androgen index
Apparent Volume of distribution [Vd/F] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Peak Plasma concentration [Cmax,ss] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Markers of liver injury 24 weeks Changes from baseline to week 24 in markers of liver injury
Area under plasma concentration vs. time curve in a 24 h dosing interval (AUCtau) after last dose (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Accumulation index calculated as a ratio of AUCtau (last dose)/AUCtau (first dose) (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Controlled attenuation parameter 24 weeks Changes from baseline to week 24 in controlled attenuation parameter measured by transient elastography/ FibroScan
Lipid and lipoprotein levels 12 and 24 weeks 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
Area under Plasma concentration vs. time curve till the last time point [AUC0-t] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Elimination rate constant [Kel] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Apparent Volume of distribution [Vd/F,ss] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
BMI 12 and 24 weeks Changes from baseline to week 12 and week 24 in BMI
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]) 24 weeks Changes from baseline to week 24 in MRI-derived measures of total liver volume
Ovarian function 12 and 24 weeks 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)
Peak Plasma concentration [Cmax] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Time to reach peak Plasma concentration [Tmax] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Area under plasma concentration vs. time curve in a 24 h dosing interval (AUCtau) after first dose (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Elimination half-life [tHalf] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Apparent Clearance [CL/F] (For Single Dose) 24 weeks Pharmacokinetics of Saroglitazar following first dose
Time to reach peak Plasma concentration [Tmax,ss] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Elimination rate constant [Kel,ss] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Elimination half-life [thalf,ss] (For Multiple Dose) 24 weeks Pharmacokinetics of Saroglitazar following last dose
Trial Locations
- Locations (19)
Zydus US002
🇺🇸San Francisco, California, United States
Zydus US008
🇺🇸Aurora, Colorado, United States
Zydus US005
🇺🇸Chandler, Arizona, United States
Zydus US004
🇺🇸Panorama City, California, United States
Zydus US010
🇺🇸Miami, Florida, United States
Zydus US001
🇺🇸Indianapolis, Indiana, United States
Zydus US011
🇺🇸Morehead City, North Carolina, United States
Zydus US003
🇺🇸Marion, Ohio, United States
Zydus US015
🇺🇸Hershey, Pennsylvania, United States
Zydus US014
🇺🇸Philadelphia, Pennsylvania, United States
Zydus US013
🇺🇸Austin, Texas, United States
Zydus US007
🇺🇸San Antonio, Texas, United States
Zydus US009
🇺🇸San Antonio, Texas, United States
Zydus MX006
🇲🇽Guadalajara, Jalisco, Mexico
Zydus MX001
🇲🇽Monterrey, Nuevo León, Mexico
Zydus MX002
🇲🇽Monterrey, Nuevo León, Mexico
Zydus MX005
🇲🇽Culiacán, Sinaloa, Mexico
Zydus MX004
🇲🇽Mérida, Yucatán, Mexico
Zydus MX003
🇲🇽Ciudad de mexico, Mexico