Evaluating Pharmacokinetic and Safety of Saroglitazar Magnesium 1 Mg When Dosed on Alternate Days in Subjects Having Moderate Hepatic Impairment with Cirrhosis Due to Cholestatic Liver Disease

Phase 1

Not yet recruiting

• Conditions: Cholestatic Liver Disease
• Interventions: Drug: Saroglitazar Magnesium 1 mg

• Registration Number: NCT06825559
• Lead Sponsor: Zydus Therapeutics Inc.

Brief Summary

Evaluating Pharmacokinetic and safety of Saroglitazar Magnesium 1 mg when dosed on alternate days in subjects having moderate hepatic impairment with cirrhosis due to cholestatic liver disease

Detailed Description

A phase 1, open-label, single arm study to evaluate pharmacokinetics, safety, and tolerability of Saroglitazar Magnesium dosed on alternate days in subjects having moderate hepatic impairment with cirrhosis due to cholestatic liver disease

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-09
• Study First Submitted QC: 2025-02-09
• Last Update Submitted: 2025-02-09
• Study First Posted: 2025-02-13
• Last Update Posted: 2025-02-13
• Study Start: 2025-03-31
• Primary Completion: 2025-08-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Male and/or female aged 18 to 80 years (both inclusive) at the time of signing the ICF.

2. Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.

3. Ability to swallow and retain oral medication.

4. Subjects having documented history of hepatic impairment with cirrhosis due to cholestatic liver disease having Child-Pugh Turcotte score 7 to 9. If the hepatic impairment classification for the subject is not the same at screening and Day -1, enrolment of the subject into a hepatic category group will be at the discretion of the investigator.

5. Laboratory test values must be clinically acceptable to the investigator and meet all the following parameters at screening:

   Alkaline Phosphatase > upper limit of normal Alanine aminotransferase/Aspartate aminotransferase value ≤ 10 × upper limit of normal Absolute neutrophil count ≥ 750/mm3 Platelets ≥ 25,000/mm3 Hemoglobin ≥ 8 g/dL α-fetoprotein <50 ng/mL or 50-80 ng/mL with negative imaging study (Ultrasound [US], computed tomography scan [CT], Magnetic Resonance Imaging [MRI]). Imaging study that excluded presence of liver cancer (US in the preceding 6 months and CT or MRI in the preceding 1 year)

6. Must provide written informed consent and agree to comply with the trial protocol.

Exclusion Criteria

1. Any significant or unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the investigator
2. History of malignancy of any type in the last 3 years of screening, with the exception of the following: in situ cervical or breast cancer or surgically excised non-melanoma skin cancers (i.e., basal cell or squamous cell carcinoma).
3. History of stomach or intestinal surgery or resection within 6 months of screening that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).
4. The history of any significant drug allergy (such as anaphylaxis) deemed clinically relevant by the investigator.
5. Any major surgery within 3 months of screening.
6. Donation of blood or blood products within 3 months of screening.
7. Active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment or symptoms of active infectious disease within 2 weeks of screening.
8. Receiving or has received any investigational drug within 30 days or 5 half-lives (whichever is longer), before receiving Saroglitazar Magnesium.
9. Estimated glomerular filtration rate (<45 mL/min/1.73 m2 by CKD-EPI 2021 formula at screening.
10. Any individual with poor peripheral venous access.
11. Receipt of blood products within 1 month of check in.
12. Human immunodeficiency virus type 1 antibody positive at screening.
13. Other known causes of liver disease, such as non-alcoholic steatohepatitis , alcoholic steatohepatitis, autoimmune hepatitis, or acute or chronic viral hepatitis (including Hepatitis B and C) as determined by the investigator and subject's medical records.
14. Subjects who have had a change in hepatic disease status within 30 days of screening, as documented by the subject's medical history and deemed clinically significant by the investigator.
15. Subjects having - History of gastrointestinal bleeding within 1 month of screening. Current functioning organ transplant. Evidence of severe ascites requiring frequent paracentesis in the opinion of the investigator.
16. Pregnancy-related exclusions, including:

Pregnant/lactating female (including positive pregnancy test at screening) Pregnancy should be avoided by male and female subjects either by true abstinence or the use of an acceptable effective contraceptive measures for the duration of the study and for at least 1 month after the end of the study treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Saroglitazar Magnesium 1 mg	Saroglitazar Magnesium 1 mg	Saroglitazar Magnesium 1 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (29 days)

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of Saroglitazar: Cmax	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	Maximum plasma concentration (Cmax)
Pharmacokinetics of Saroglitazar: Tmax	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	Time to reach maximum plasma concentration (Tmax)
Pharmacokinetics of Saroglitazar: AUCt	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The area under plasma concentration vs. time curve till the last time point
Pharmacokinetics of Saroglitazar: AUCi	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The area under plasma concentration vs. time curve extrapolated to the infinity
Pharmacokinetics of Saroglitazar: Kel	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The elimination rate constant
Pharmacokinetics of Saroglitazar: AUCtau	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The area under plasma concentration vs. time curve in a 48 hours dosing interval
Pharmacokinetics of Saroglitazar: t1/2	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The elimination half-life
Pharmacokinetics of Saroglitazar: Vd/F	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The apparent volume of distribution
Pharmacokinetics of Saroglitazar: CL/F	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The apparent clearance

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability of Saroglitazar Magnesium	From baseline to End of study (35 days)	Number of participants with adverse events
Pharmacokinetics of Saroglitazar sulfoxide: Tmax	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	Time to reach maximum plasma concentration
Pharmacokinetics of Saroglitazar sulfoxide: Cmax	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	Maximum plasma concentration
Pharmacokinetics of Saroglitazar sulfoxide: CL/F	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The apparent clearance
Pharmacokinetics of Saroglitazar sulfoxide: Vd/F	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The apparent volume of distribution
Pharmacokinetics of Saroglitazar sulfoxide: t1/2	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The elimination half-life
Pharmacokinetics of Saroglitazar sulfoxide: AUCtau	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The area under plasma concentration vs. time curve in a 48 hours dosing interval
Pharmacokinetics of Saroglitazar sulfoxide: Kel	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The elimination rate constant
Pharmacokinetics of Saroglitazar sulfoxide: AUCi	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The area under plasma concentration vs. time curve extrapolated to the infinity
Pharmacokinetics of Saroglitazar sulfoxide: AUCt	PK sampling timepoints: pre- dose, 20 min, 40 min, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36, and 48 hours post-dose of Day 1 and Day 29	The area under plasma concentration vs. time curve extrapolated to the infinity
Change from baseline in alkaline phosphatase levels	From baseline to end of treatment (29 days)