Clinical trial NCT03617263: Saroglitazar Magnesium 4 mg in the Treatment of NAFLD in Women With PCOS (EVIDENCES VII)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-alcoholic Fatty Liver Disease in Women With PCOS
Keywords: NAFLD
PCOS
Saroglitazar Magnesium
Lead sponsor: Zydus Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2018-08-06
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hepatic fat content
timeFrame: 24 weeks
Secondary outcomes:
measure: Liver enzymes/LFTs
timeFrame: 12 and 24 weeks
measure: Insulin resistance
timeFrame: 12 and 24 weeks
measure: Markers of liver injury
timeFrame: 24 weeks
measure: Liver fibrosis
timeFrame: 24 weeks
measure: Liver stiffness
timeFrame: 24 weeks
measure: Controlled attenuation parameter
timeFrame: 24 weeks
measure: BMI
timeFrame: 12 and 24 weeks
measure: Waist circumference
timeFrame: 12 and 24 weeks
measure: 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)
timeFrame: 24 weeks
measure: 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])
timeFrame: 24 weeks
measure: Lipid and lipoprotein levels
timeFrame: 12 and 24 weeks
measure: SHBG level
timeFrame: 12 and 24 weeks
measure: Ovarian function
timeFrame: 12 and 24 weeks
measure: 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.
timeFrame: 12 and 24 weeks
measure: Peak Plasma concentration [Cmax] (For Single Dose)
timeFrame: 24 weeks
measure: Time to reach peak Plasma concentration [Tmax] (For Single Dose)
timeFrame: 24 weeks
measure: Area under Plasma concentration vs. time curve till the last time point [AUC0-t] (For Single Dose)
timeFrame: 24 weeks
measure: Area under Plasma concentration vs. time curve extrapolated to the infinity (AUC0-∞) after first dose (For Single Dose)
timeFrame: 24 weeks
measure: Area under plasma concentration vs. time curve in a 24 h dosing interval (AUCtau) after first dose (For Single Dose)
timeFrame: 24 weeks
measure: Elimination rate constant [Kel] (For Single Dose)
timeFrame: 24 weeks
measure: Elimination half-life [tHalf] (For Single Dose)
timeFrame: 24 weeks
measure: Apparent Volume of distribution [Vd/F] (For Single Dose)
timeFrame: 24 weeks
measure: Apparent Clearance [CL/F] (For Single Dose)
timeFrame: 24 weeks
measure: Peak Plasma concentration [Cmax,ss] (For Multiple Dose)
timeFrame: 24 weeks
measure: Time to reach peak Plasma concentration [Tmax,ss] (For Multiple Dose)
timeFrame: 24 weeks
measure: Area under plasma concentration vs. time curve in a 24 h dosing interval (AUCtau) after last dose (For Multiple Dose)
timeFrame: 24 weeks
measure: Elimination rate constant [Kel,ss] (For Multiple Dose)
timeFrame: 24 weeks
measure: Elimination half-life [thalf,ss] (For Multiple Dose)
timeFrame: 24 weeks
measure: Apparent Volume of distribution [Vd/F,ss] (For Multiple Dose)
timeFrame: 24 weeks
measure: Apparent Clearance [CL/F,ss] (For Multiple Dose)
timeFrame: 24 weeks
measure: Minimal or Trough plasma concentration [Cmin] (For Multiple Dose)
timeFrame: 24 weeks
measure: Fluctuation index (For Multiple Dose)
timeFrame: 24 weeks
measure: Accumulation index calculated as a ratio of AUCtau (last dose)/AUCtau (first dose) (For Multiple Dose)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Zydus US005
state: Arizona
city: Panorama City
country: United States
facility: Zydus US004
state: California
city: San Francisco
country: United States
facility: Zydus US002
state: California
city: Aurora
country: United States
facility: Zydus US008
state: Colorado
city: Miami
country: United States
facility: Zydus US010
state: Florida
city: Indianapolis
country: United States
facility: Zydus US001
state: Indiana
city: Morehead City
country: United States
facility: Zydus US011
state: North Carolina
city: Marion
country: United States
facility: Zydus US003
state: Ohio
city: Hershey
country: United States
facility: Zydus US015
state: Pennsylvania
city: Philadelphia
country: United States
facility: Zydus US014
state: Pennsylvania
city: Austin
country: United States
facility: Zydus US013
state: Texas
city: San Antonio
country: United States
facility: Zydus US007
state: Texas
city: San Antonio
country: United States
facility: Zydus US009
state: Texas
city: Guadalajara
country: Mexico
facility: Zydus MX006
state: Jalisco
city: Monterrey
country: Mexico
facility: Zydus MX001
state: Nuevo León
city: Monterrey
country: Mexico
facility: Zydus MX002
state: Nuevo León
city: Culiacán
country: Mexico
facility: Zydus MX005
state: Sinaloa
city: Mérida
country: Mexico
facility: Zydus MX004
state: Yucatán
city: Ciudad de mexico
country: Mexico
facility: Zydus MX003
Study officials:
affiliation: Zydus Therapeutics Inc.
name: Deven Parmar, MD
role: STUDY_DIRECTOR
References:
citation: 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.