Evaluate PK & Safety of Saroglitazar in Subjects With Moderate Hepatic Impairment Due to Cholestatic Liver Disease

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

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

Study Overview

• Status: Recruiting
• Conditions: Cholestatic Liver Disease
• Intervention / Treatment: Drug: Saroglitazar Magnesium 1 mg

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 Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Farheen Shaikh; Phone Number: 221 609-730-1900; Email: fshaikh@zydustherapeutics.com
• Study Contact Backup: Name: Deven Parmar; Phone Number: 609-559-0765; Email: dparmar@zydustherapeutics.com

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Zydus Site US001
      • Contact: Mandy Cruz; Email: mandcruz@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saroglitazar Magnesium 1 mg; Saroglitazar Magnesium 1 mg tablet orally administered on alternate days in the morning before breakfast without food, for the duration of treatment (29 days)	Drug: Saroglitazar Magnesium 1 mg; Saroglitazar Magnesium 1 mg will be assigned to all participants enrolled in this open label study; Other Names: Not any

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Saroglitazar: Cmax	Maximum plasma concentration (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
Pharmacokinetics of Saroglitazar: Tmax	Time to reach maximum plasma concentration (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
Pharmacokinetics of Saroglitazar: AUCt	The area under plasma concentration vs. time curve till the last time point	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
Pharmacokinetics of Saroglitazar: AUCi	The area under plasma concentration vs. time curve extrapolated to the infinity	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
Pharmacokinetics of Saroglitazar: Kel	The elimination rate constant	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
Pharmacokinetics of Saroglitazar: AUCtau	The area under plasma concentration vs. time curve in a 48 hours dosing interval	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
Pharmacokinetics of Saroglitazar: t1/2	The elimination half-life	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
Pharmacokinetics of Saroglitazar: Vd/F	The apparent volume of distribution	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
Pharmacokinetics of Saroglitazar: CL/F	The apparent clearance	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Saroglitazar sulfoxide: Tmax	Time to reach maximum plasma concentration	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
Pharmacokinetics of Saroglitazar sulfoxide: Cmax	Maximum plasma concentration	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
Pharmacokinetics of Saroglitazar sulfoxide: CL/F	The apparent clearance	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
Pharmacokinetics of Saroglitazar sulfoxide: Vd/F	The apparent volume of distribution	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
Pharmacokinetics of Saroglitazar sulfoxide: t1/2	The elimination half-life	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
Pharmacokinetics of Saroglitazar sulfoxide: AUCtau	The area under plasma concentration vs. time curve in a 48 hours dosing interval	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
Pharmacokinetics of Saroglitazar sulfoxide: Kel	The elimination rate constant	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
Pharmacokinetics of Saroglitazar sulfoxide: AUCi	The area under plasma concentration vs. time curve extrapolated to the infinity	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
Pharmacokinetics of Saroglitazar sulfoxide: AUCt	The area under plasma concentration vs. time curve extrapolated to the infinity	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
Change from baseline in alkaline phosphatase levels		From baseline to end of treatment (29 days)
Number of participants with adverse events [Safety and Tolerability]	Number of participants with adverse events	From baseline to End of study (35 days)

Collaborators and Investigators

• Sponsor: Zydus Therapeutics Inc.
• Investigators: Study Director: Deven Parmar, Zydus Therapeutics Inc.

Publications and helpful links

General Publications

• Rodney P, Starzomski R. Constraints on the moral agency of nurses. Rhinology. 1993 Oct;69(9):23-6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 9, 2025
• First Submitted That Met QC Criteria: February 9, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Primary Biliary Cholangitis; PBC; Saroglitazar Magnesium
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis, Biliary; saroglitazar
• Other Study ID Numbers: SARO.24.003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No