Non-alcoholic Fatty Liver Disease in Women With PCOS
Conditions
Keywords
NAFLD, PCOS, Saroglitazar Magnesium
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.
Interventions
DRUGSaroglitazar Magnesium 4 mg Tablet
Patients randomly assigned to this group will receive Saroglitazar Magnesium orally once daily for 24 weeks.
DRUGPlacebo
Patients randomly assigned to this group will receive Placebo tablet orally once daily for 24 weeks.
Sponsors
Zydus Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Fat Content | 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
| Measure | Time frame | Description |
|---|---|---|
| Liver Enzymes/Liver Function Tests | Baseline, Week 12, and Week 24 | Changes from baseline to week 12 and week 24 in Alkaline phosphatase |
| Insulin Resistance | Baseline, Week 12, and Week 24 | Evaluation of HOMA of Insulin Resistance Index determines insulin resistance and estimates insulin sensitivity, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance |
| Liver Injury | Baseline and Week 24 | Changes from baseline to week 24 in Liver Injury, including Cytokeratin (CK)-18. CK18 \[M30\] and CK-18 \[M-65\] were measured as biomarkers of hepatocyte apoptosis. Both are important indicators for liver tissue conditions and effectively reflect hepatocyte damage. A negative change from baseline indicates a decrease in hepatocyte apoptosis or a decrease in hepatocyte damage. |
| Liver Stiffness | Baseline and Week 24 | Changes from baseline to week 24 in liver stiffness measured by transient elastography/FibroScan |
| Controlled Attenuation Parameter | Baseline and Week 24 | Changes from baseline to week 24 in controlled attenuation parameter measured by transient elastography/ FibroScan |
| Body Mass Index (BMI) | Baseline, Week 12, and Week 24 | Changes from baseline to week 12 and week 24 in Body mass index |
| Waist Circumference | Baseline, Week 12, and Week 24 | Changes from baseline to week 12 and week 24 in waist circumference |
| Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Fat Index | Baseline and Week 24 | MRI-derived measures of total liver fat index. Total liver volume: The total liver volume was calculated through a process requiring segmentation image analysis. Liver volume was calculated after complete segmentation by summing the liver surface area at each segmented slice and then multiplying this sum by individual slice thickness, in milliliters (mL). Total liver fat index: The total liver fat index (TLFI, units: % mL) took into consideration the volume of liver from which proton-density fat fraction was derived. It was 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 Volume | Baseline and Week 24 | 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 \[mL\]) |
| Lipid and Lipoprotein Levels | Baseline, Week 12, and Week 24 | Changes from baseline to week 12 and week 24 in Triglyceride (TG) |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| Sex Hormone Binding Globulin (SHBG) Level | Baseline, Week 12, and Week 24 | Changes from baseline in SHBG level |
| Ovarian Function | Baseline, Week 12, and Week 24 | Changes from baseline in 17-hydroxyprogesterone |
| Changes From Baseline to Week 12 and Week 24 in Free Androgen Index | Baseline, Week 12, and Week 24 | Free androgen index is a ratio used to determine abnormal androgen status in humans, measured by Total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by a constant, usually 100. A higher score indicates a worse outcome (more androgenic). |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | 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) | 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following the last dose. It is calculated as (Cmax - Cmin) / Cavg. The value has been multiplied by 100, hence has been expressed in percentage unit; where Cmax is the Maximum measured plasma concentration at steady state, Cmin is Minimal or trough plasma concentration at steady state, and Cavg is Average concentration = AUCtau,ss /tau. |
| 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) | Pharmacokinetics of Saroglitazar following last dose |
| 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) | Pharmacokinetics of Saroglitazar following first dose |
Countries
Mexico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saroglitazar Magnesium 4 mg Saroglitazar Magnesium once daily in the morning before breakfast
Saroglitazar Magnesium 4 mg Tablet: Patients randomly assigned to this group will receive Saroglitazar Magnesium orally once daily for 24 weeks. | 30 |
| Placebo Placebo tablet once daily in the morning before breakfast
Placebo: Patients randomly assigned to this group will receive Placebo tablet orally once daily for 24 weeks. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Saroglitazar Magnesium 4 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 28.5 years STANDARD_DEVIATION 7.16 | 27.2 years STANDARD_DEVIATION 5.79 | 27.9 years STANDARD_DEVIATION 6.49 |
| BMI | 40.14 kg/m^2 STANDARD_DEVIATION 7.636 | 37.81 kg/m^2 STANDARD_DEVIATION 6.981 | 38.97 kg/m^2 STANDARD_DEVIATION 7.348 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 21 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 9 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Mestizo | 9 participants | 13 participants | 22 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 20 participants | 15 participants | 35 participants |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 19 / 30 | 22 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Hepatic Fat Content
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)
Time frame: Baseline and Week 24
Population: Per Protocol (PP) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Hepatic Fat Content | -3.1741 percentage of liver fat | Standard Error 1.018 |
| Placebo | Hepatic Fat Content | -0.3499 percentage of liver fat | Standard Error 1.06137 |
p-value: 0.0613ANCOVA
Secondary
Accumulation Index Calculated as a Ratio of AUCtau (Last Dose)/AUCtau (First Dose) (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Accumulation Index Calculated as a Ratio of AUCtau (Last Dose)/AUCtau (First Dose) (For Multiple Dose) | 1.113 ratio | Standard Deviation 0.264 |
Secondary
Apparent Clearance [CL/F] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Apparent Clearance [CL/F] (For Single Dose) | 9.305 L/hr | Standard Deviation 3.599 |
Secondary
Apparent Clearance [CL/F,ss] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Apparent Clearance [CL/F,ss] (For Multiple Dose) | 8.883 L/hr | Standard Deviation 2.444 |
Secondary
Apparent Volume of Distribution [Vd/F] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Apparent Volume of Distribution [Vd/F] (For Single Dose) | 77.890 L | Standard Deviation 42.887 |
Secondary
Apparent Volume of Distribution [Vd/F,ss] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Apparent Volume of Distribution [Vd/F,ss] (For Multiple Dose) | 66.047 L | Standard Deviation 28.325 |
Secondary
Area Under Plasma Concentration vs. Time Curve Extrapolated to the Infinity (AUC0-∞) After First Dose (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Area Under Plasma Concentration vs. Time Curve Extrapolated to the Infinity (AUC0-∞) After First Dose (For Single Dose) | 473.771 ng/mL*hr | Standard Deviation 182.43 |
Secondary
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
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Area Under Plasma Concentration vs. Time Curve in a 24 h Dosing Interval (AUCtau) After First Dose (For Single Dose) | 491.981 ng*hr/mL | Standard Deviation 192.373 |
Secondary
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
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Area Under Plasma Concentration vs. Time Curve in a 24 h Dosing Interval (AUCtau) After Last Dose (For Multiple Dose) | 454.916 ng*hr/mL | Standard Deviation 162.275 |
Secondary
Area Under Plasma Concentration vs. Time Curve Till the Last Time Point [AUC0-t] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Area Under Plasma Concentration vs. Time Curve Till the Last Time Point [AUC0-t] (For Single Dose) | 486.033 ng*hr/mL | Standard Deviation 188.32 |
Secondary
Body Mass Index (BMI)
Changes from baseline to week 12 and week 24 in Body mass index
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Body Mass Index (BMI) | Week 12 | 0.101 kg/m^2 | Standard Error 0.2817 |
| Saroglitazar Magnesium 4 mg | Body Mass Index (BMI) | Week 24 | 0.273 kg/m^2 | Standard Error 0.3132 |
| Placebo | Body Mass Index (BMI) | Week 12 | 0.272 kg/m^2 | Standard Error 0.3003 |
| Placebo | Body Mass Index (BMI) | Week 24 | -0.066 kg/m^2 | Standard Error 0.3266 |
Comparison: Week 12p-value: 0.68ANCOVA
Comparison: Week 24p-value: 0.4587ANCOVA
Secondary
Changes From Baseline to Week 12 and Week 24 in Free Androgen Index
Free androgen index is a ratio used to determine abnormal androgen status in humans, measured by Total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by a constant, usually 100. A higher score indicates a worse outcome (more androgenic).
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Changes From Baseline to Week 12 and Week 24 in Free Androgen Index | Week 12 | -0.371 Ratio | Standard Error 0.1637 |
| Saroglitazar Magnesium 4 mg | Changes From Baseline to Week 12 and Week 24 in Free Androgen Index | Week 24 | -0.253 Ratio | Standard Error 0.1742 |
| Placebo | Changes From Baseline to Week 12 and Week 24 in Free Androgen Index | Week 12 | -0.483 Ratio | Standard Error 0.1746 |
| Placebo | Changes From Baseline to Week 12 and Week 24 in Free Androgen Index | Week 24 | -0.256 Ratio | Standard Error 0.1816 |
Comparison: Week 12p-value: 0.6434ANCOVA
Comparison: Week 24p-value: 0.9895ANCOVA
Secondary
Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Fat Index
MRI-derived measures of total liver fat index. Total liver volume: The total liver volume was calculated through a process requiring segmentation image analysis. Liver volume was calculated after complete segmentation by summing the liver surface area at each segmented slice and then multiplying this sum by individual slice thickness, in milliliters (mL). Total liver fat index: The total liver fat index (TLFI, units: % mL) took into consideration the volume of liver from which proton-density fat fraction was derived. It was calculated as the product of liver volume and the liver mean proton-density fat fraction across all liver segments.
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Fat Index | -78.493 %mL | Standard Error 38.0001 |
| Placebo | Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Fat Index | -8.963 %mL | Standard Error 37.1636 |
p-value: 0.1983ANCOVA
Secondary
Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Volume
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 \[mL\])
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Volume | -66.886 mL | Standard Error 70.3776 |
| Placebo | Changes From Baseline to Week 24 in MRI-derived Measures of Total Liver Volume | -36.176 mL | Standard Error 68.8178 |
p-value: 0.7576ANCOVA
Secondary
Controlled Attenuation Parameter
Changes from baseline to week 24 in controlled attenuation parameter measured by transient elastography/ FibroScan
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Controlled Attenuation Parameter | -18.84 dB/m | Standard Error 9.119 |
| Placebo | Controlled Attenuation Parameter | -3.40 dB/m | Standard Error 9.521 |
p-value: 0.2559ANCOVA
Secondary
Elimination Half-life [tHalf] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Elimination Half-life [tHalf] (For Single Dose) | 5.317 hr | Standard Deviation 1.559 |
Secondary
Elimination Half-life [Thalf,ss] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Elimination Half-life [Thalf,ss] (For Multiple Dose) | 5.196 hour | Standard Deviation 1.79 |
Secondary
Elimination Rate Constant [Kel] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Elimination Rate Constant [Kel] (For Single Dose) | 0.144 1/hr | Standard Deviation 0.057 |
Secondary
Elimination Rate Constant [Kel,ss] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Elimination Rate Constant [Kel,ss] (For Multiple Dose) | 0.147 1/hr | Standard Deviation 0.047 |
Secondary
Fluctuation Index (For Multiple Dose)
Pharmacokinetics of Saroglitazar following the last dose. It is calculated as (Cmax - Cmin) / Cavg. The value has been multiplied by 100, hence has been expressed in percentage unit; where Cmax is the Maximum measured plasma concentration at steady state, Cmin is Minimal or trough plasma concentration at steady state, and Cavg is Average concentration = AUCtau,ss /tau.
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Fluctuation Index (For Multiple Dose) | 676.702 percentage | Standard Deviation 240.892 |
Secondary
Insulin Resistance
Evaluation of HOMA of Insulin Resistance Index determines insulin resistance and estimates insulin sensitivity, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Insulin Resistance | Week 12 | -1.983 Index | Standard Error 1.2192 |
| Saroglitazar Magnesium 4 mg | Insulin Resistance | Week 24 | 0.498 Index | Standard Error 2.191 |
| Placebo | Insulin Resistance | Week 12 | 1.081 Index | Standard Error 1.3004 |
| Placebo | Insulin Resistance | Week 24 | 4.303 Index | Standard Error 2.2852 |
Comparison: Week 12p-value: 0.0941ANCOVA
Comparison: Week 24p-value: 0.2378ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline to week 12 and week 24 in Low-density lipoprotein (LDL)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | -10.318 mg/dL | Standard Error 3.7934 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -13.457 mg/dL | Standard Error 3.0454 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -4.821 mg/dL | Standard Error 4.0492 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | -4.938 mg/dL | Standard Error 3.1785 |
Comparison: Week 12p-value: 0.3323ANCOVA
Comparison: Week 24p-value: 0.0624ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline to week 12 and week 24 in Triglyceride (TG)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | -41.535 mg/dL | Standard Error 12.3535 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -47.886 mg/dL | Standard Error 15.8642 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -21.665 mg/dL | Standard Error 13.1733 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | 14.724 mg/dL | Standard Error 16.5423 |
Comparison: Week 12p-value: 0.2784ANCOVA
Comparison: Week 24p-value: 0.0091ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline to week 12 and week 24 in Total cholesterol (TC)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | -16.807 mg/dL | Standard Error 3.8832 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -22.650 mg/dL | Standard Error 3.7464 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -6.992 mg/dL | Standard Error 4.1447 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | -3.120 mg/dL | Standard Error 3.9095 |
Comparison: Week 12p-value: 0.0941ANCOVA
p-value: 0.0009ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline to week 12 and week 24 in High-density lipoprotein
Time frame: Baseline, Week 12, and Week 24
Population: PP Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | 2.327 mg/dL | Standard Error 1.311 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | 0.676 mg/dL | Standard Error 1.4851 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -0.599 mg/dL | Standard Error 1.3986 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | -1.561 mg/dL | Standard Error 1.5491 |
Comparison: Week 12p-value: 0.1363ANCOVA
Comparison: Week 24p-value: 0.3057ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline to week 12 and week 24 in Small dense low density lipoprotein (sdLDL)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | -6.918 mg/dL | Standard Error 2.0576 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -9.000 mg/dL | Standard Error 1.951 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -4.889 mg/dL | Standard Error 2.1943 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | -2.574 mg/dL | Standard Error 2.0346 |
Comparison: Week 12p-value: 0.505ANCOVA
Comparison: Week 24p-value: 0.0279ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline to week 12 and week 24 in Very low density lipoprotein (VLDL)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | -7.102 mg/dL | Standard Error 2.5927 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -8.736 mg/dL | Standard Error 2.9168 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -3.521 mg/dL | Standard Error 2.7645 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | 3.452 mg/dL | Standard Error 3.0413 |
Comparison: Week 12p-value: 0.3508ANCOVA
Comparison: Week 24p-value: 0.0059ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline apolipoprotein A
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | 4.486 mg/dL | Standard Error 3.876 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -2.830 mg/dL | Standard Error 3.1112 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | 2.130 mg/dL | Standard Error 4.1326 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | -1.272 mg/dL | Standard Error 3.2442 |
Comparison: Week 12p-value: 0.68ANCOVA
Comparison: Week 24p-value: 0.731ANCOVA
Secondary
Lipid and Lipoprotein Levels
Changes from baseline in apolipoprotein B
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 12 | -10.673 mg/dL | Standard Error 2.7834 |
| Saroglitazar Magnesium 4 mg | Lipid and Lipoprotein Levels | Week 24 | -13.146 mg/dL | Standard Error 2.306 |
| Placebo | Lipid and Lipoprotein Levels | Week 12 | -3.508 mg/dL | Standard Error 2.9723 |
| Placebo | Lipid and Lipoprotein Levels | Week 24 | -3.233 mg/dL | Standard Error 2.4071 |
Comparison: Week 12p-value: 0.0896ANCOVA
Comparison: Week 24p-value: 0.0053ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in Alkaline phosphatase
Time frame: Baseline, Week 12, and Week 24
Population: Per Protocol (PP) population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | -22.64 U/L | Standard Error 1.954 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | -20.07 U/L | Standard Error 2.52 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | -3.91 U/L | Standard Error 2.083 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | -1.66 U/L | Standard Error 2.627 |
Comparison: Week 12p-value: <0.0001ANCOVA
Comparison: Week 24p-value: <0.0001ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in Alanine aminotransferase
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | -22.00 U/L | Standard Error 4.586 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | -25.73 U/L | Standard Error 4.276 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | -4.72 U/L | Standard Error 4.894 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | -8.30 U/L | Standard Error 4.462 |
Comparison: Week 12p-value: 0.0142ANCOVA
Comparison: Week 24p-value: 0.0077ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in Aspartate Aminotransferase
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | -9.97 U/L | Standard Error 4.233 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | -11.27 U/L | Standard Error 4.437 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | -3.31 U/L | Standard Error 4.514 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | -2.88 U/L | Standard Error 4.627 |
Comparison: Week 12p-value: 0.2893ANCOVA
Comparison: Week 24p-value: 0.1989ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in gamma-glutamyl transferase
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | -22.62 U/L | Standard Error 2.629 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | -21.46 U/L | Standard Error 2.545 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | -1.52 U/L | Standard Error 2.807 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | -2.37 U/L | Standard Error 2.656 |
Comparison: Week 12p-value: <0.0001ANCOVA
Comparison: Week 24p-value: <0.0001ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in serum protein
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | 0.01 g/L | Standard Error 0.072 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | -0.14 g/L | Standard Error 0.071 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | 0.02 g/L | Standard Error 0.077 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | 0.03 g/L | Standard Error 0.074 |
Comparison: Week 12p-value: 0.8664ANCOVA
Comparison: Week 24p-value: 0.1137ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in albumin
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | 1.06 g/L | Standard Error 0.477 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | 0.06 g/L | Standard Error 0.485 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | -0.39 g/L | Standard Error 0.51 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | -0.15 g/L | Standard Error 0.507 |
Comparison: Week 12p-value: 0.0487ANCOVA
Comparison: Week 24p-value: 0.7743ANCOVA
Secondary
Liver Enzymes/Liver Function Tests
Changes from baseline to week 12 and week 24 in total bilirubin.
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 12 | -0.076 mg/dL | Standard Error 0.0294 |
| Saroglitazar Magnesium 4 mg | Liver Enzymes/Liver Function Tests | Week 24 | -0.066 mg/dL | Standard Error 0.029 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 12 | -0.008 mg/dL | Standard Error 0.0313 |
| Placebo | Liver Enzymes/Liver Function Tests | Week 24 | -0.004 mg/dL | Standard Error 0.0302 |
Comparison: Week 12p-value: 0.1174ANCOVA
Comparison: Week 24p-value: 0.1483ANCOVA
Secondary
Liver Injury
Changes from baseline to week 24 in Liver Injury, including Cytokeratin (CK)-18. CK18 \[M30\] and CK-18 \[M-65\] were measured as biomarkers of hepatocyte apoptosis. Both are important indicators for liver tissue conditions and effectively reflect hepatocyte damage. A negative change from baseline indicates a decrease in hepatocyte apoptosis or a decrease in hepatocyte damage.
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Injury | M30 | -238.801 U/L | Standard Error 69.9009 |
| Saroglitazar Magnesium 4 mg | Liver Injury | M65 | -260.232 U/L | Standard Error 100.6148 |
| Placebo | Liver Injury | M30 | -92.160 U/L | Standard Error 72.889 |
| Placebo | Liver Injury | M65 | -72.273 U/L | Standard Error 104.9207 |
Comparison: CK-18 Fragment - M30p-value: 0.1542ANCOVA
Comparison: CK-18 Fragment - M65p-value: 0.2037ANCOVA
Secondary
Liver Injury
Changes from baseline to week 24 in high-sensitivity C-reactive protein (hs-CRP)
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Injury | -1.00 mg/L | Standard Error 1.381 |
| Placebo | Liver Injury | 0.55 mg/L | Standard Error 1.44 |
p-value: 0.4431ANCOVA
Secondary
Liver Injury
Changes from baseline to week 24 in Tumor necrosis factor (TNFα)
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Injury | 0.109 ng/L | Standard Error 0.2711 |
| Placebo | Liver Injury | 0.587 ng/L | Standard Error 0.2827 |
p-value: 0.2289ANCOVA
Secondary
Liver Stiffness
Changes from baseline to week 24 in liver stiffness measured by transient elastography/FibroScan
Time frame: Baseline and Week 24
Population: PP population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Liver Stiffness | -0.75 kPa | Standard Error 0.953 |
| Placebo | Liver Stiffness | 1.67 kPa | Standard Error 0.994 |
p-value: 0.0853ANCOVA
Secondary
Minimal or Trough Plasma Concentration [Cmin] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Minimal or Trough Plasma Concentration [Cmin] (For Multiple Dose) | 1.053 ng/mL | Standard Deviation 0.825 |
Secondary
Ovarian Function
Changes from baseline in 17-hydroxyprogesterone
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | 8.800 ng/dL | Standard Error 9.7348 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -10.325 ng/dL | Standard Error 6.8372 |
| Placebo | Ovarian Function | Week 12 | -4.819 ng/dL | Standard Error 10.3892 |
| Placebo | Ovarian Function | Week 24 | -2.168 ng/dL | Standard Error 7.1337 |
Comparison: Week 12p-value: 0.3482ANCOVA
Comparison: Week 24p-value: 0.4176ANCOVA
Secondary
Ovarian Function
Changes from baseline in Total testosterone
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | -0.173 nmol/L | Standard Error 0.1134 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -0.231 nmol/L | Standard Error 0.1182 |
| Placebo | Ovarian Function | Week 12 | -0.171 nmol/L | Standard Error 0.1209 |
| Placebo | Ovarian Function | Week 24 | -0.073 nmol/L | Standard Error 0.1233 |
p-value: 0.993ANCOVA
Comparison: Week 24p-value: 0.3612ANCOVA
Secondary
Ovarian Function
Changes from baseline in estradiol
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | -57.237 pmol/L | Standard Error 41.402 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -105.380 pmol/L | Standard Error 65.5983 |
| Placebo | Ovarian Function | Week 12 | -24.045 pmol/L | Standard Error 44.1354 |
| Placebo | Ovarian Function | Week 24 | 17.209 pmol/L | Standard Error 68.393 |
Comparison: Week 12p-value: 0.5862ANCOVA
Comparison: Week 24p-value: 0.2026ANCOVA
Secondary
Ovarian Function
Changes from baseline in LH-to-FSH ratio
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | -0.230 Ratio | Standard Error 0.1731 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -0.324 Ratio | Standard Error 0.2226 |
| Placebo | Ovarian Function | Week 12 | 0.064 Ratio | Standard Error 0.1808 |
| Placebo | Ovarian Function | Week 24 | 0.136 Ratio | Standard Error 0.2326 |
Comparison: Week 12p-value: 0.2475ANCOVA
Comparison: Week 24p-value: 0.1621ANCOVA
Secondary
Ovarian Function
Changes from baseline in luteinizing hormone (LH)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -1.305 IU/L | Standard Error 1.202 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | -1.140 IU/L | Standard Error 0.8881 |
| Placebo | Ovarian Function | Week 24 | 0.140 IU/L | Standard Error 1.2532 |
| Placebo | Ovarian Function | Week 12 | -1.632 IU/L | Standard Error 0.9467 |
Comparison: Week 12p-value: 0.7065ANCOVA
Comparison: Week 24p-value: 0.4096ANCOVA
Secondary
Ovarian Function
Changes from baseline in follicle-stimulating hormone (FSH)
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | -0.892 IU/L | Standard Error 0.3356 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -0.689 IU/L | Standard Error 0.3196 |
| Placebo | Ovarian Function | Week 12 | -1.722 IU/L | Standard Error 0.358 |
| Placebo | Ovarian Function | Week 24 | -1.125 IU/L | Standard Error 0.3334 |
Comparison: Week 12p-value: 0.0994ANCOVA
Comparison: Week 24p-value: 0.3527ANCOVA
Secondary
Ovarian Function
Changes from baseline in free testosterone
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 12 | -0.005 nmol/L | Standard Error 0.0028 |
| Saroglitazar Magnesium 4 mg | Ovarian Function | Week 24 | -0.005 nmol/L | Standard Error 0.0028 |
| Placebo | Ovarian Function | Week 12 | -0.009 nmol/L | Standard Error 0.003 |
| Placebo | Ovarian Function | Week 24 | -0.003 nmol/L | Standard Error 0.0029 |
Comparison: Week 12p-value: 0.4373ANCOVA
Comparison: Week 24p-value: 0.6248ANCOVA
Secondary
Peak Plasma Concentration [Cmax] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Peak Plasma Concentration [Cmax] (For Single Dose) | 120.250 ng/mL | Standard Deviation 49.997 |
Secondary
Peak Plasma Concentration [Cmax,ss] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Peak Plasma Concentration [Cmax,ss] (For Multiple Dose) | 137.210 ng/mL | Standard Deviation 57.77 |
Secondary
Sex Hormone Binding Globulin (SHBG) Level
Changes from baseline in SHBG level
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Sex Hormone Binding Globulin (SHBG) Level | Week 12 | 17.182 nmol/L | Standard Error 13.1496 |
| Saroglitazar Magnesium 4 mg | Sex Hormone Binding Globulin (SHBG) Level | Week 24 | -3.882 nmol/L | Standard Error 8.0521 |
| Placebo | Sex Hormone Binding Globulin (SHBG) Level | Week 12 | 27.506 nmol/L | Standard Error 14.0281 |
| Placebo | Sex Hormone Binding Globulin (SHBG) Level | Week 24 | 8.286 nmol/L | Standard Error 8.3982 |
Comparison: Week 12p-value: 0.5962ANCOVA
Comparison: Week 24p-value: 0.3035ANCOVA
Secondary
Time to Reach Peak Plasma Concentration [Tmax] (For Single Dose)
Pharmacokinetics of Saroglitazar following first dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Time to Reach Peak Plasma Concentration [Tmax] (For Single Dose) | 1.902 hour | Standard Deviation 1.103 |
Secondary
Time to Reach Peak Plasma Concentration [Tmax,ss] (For Multiple Dose)
Pharmacokinetics of Saroglitazar following last dose
Time frame: 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)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Time to Reach Peak Plasma Concentration [Tmax,ss] (For Multiple Dose) | 1.667 hour | Standard Deviation 0.866 |
Secondary
Waist Circumference
Changes from baseline to week 12 and week 24 in waist circumference
Time frame: Baseline, Week 12, and Week 24
Population: PP population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Saroglitazar Magnesium 4 mg | Waist Circumference | Week 12 | 1.285 cm | Standard Error 0.9879 |
| Saroglitazar Magnesium 4 mg | Waist Circumference | Week 24 | 1.607 cm | Standard Error 0.8919 |
| Placebo | Waist Circumference | Week 12 | 1.142 cm | Standard Error 1.0783 |
| Placebo | Waist Circumference | Week 24 | 1.127 cm | Standard Error 0.93 |
Comparison: Week 12p-value: 0.923ANCOVA
Comparison: Week 24p-value: 0.7115ANCOVA