Hepatic Impairment With Cirrhosis Due to Cholestatic Liver Disease

NCT05045482 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SARO.19.003 Part B
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, Open-label Extension Groups Study in Subjects having Hepatic Impairment with Cirrhosis due to Cholestatic Liver Disease

Conditions

Hepatic Impairment; Cirrhosis; Cholestatic Liver Disease

Keywords

Hepatic Impairment; Saroglitazar Magnesium; Cirrhosis; Cholestatic Liver Disease

Outcome Measures

Primary Outcomes (7)

• To evaluate the plasma PK of Saroglitazar (parent compound)

  To measure the plasma concentration of Saroglitazar (parent compound) and estimate the AUCt following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.

  Serial PK blood samples will be collected on Day1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)

• To assess the safety and tolerability of Saroglitazar

  Percentage of subjects with clinical \& laboratory AEs/SAEs and Treatment emergent AEs/SAEs, coded using the MedDRA following single and once a daily multiple oral doses of 1 mg and 2 mg of Saroglitazar Magnesium in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function

  Through study completion, an average of 9 weeks

• To evaluate plasma PK of Saroglitazar metabolite (Saroglitazar sulfoxide)

  To measure the plasma concentration of Saroglitazar metabolite (Saroglitazar sulfoxide) and estimate the AUCt following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.

  Serial PK blood samples will be collected on Day 1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)

• To evaluate the impact of hepatic impairment with cirrhosis due to cholestatic liver disease on the unbound concentration of Saroglitazar in systemic circulation in

  To measure the differences (between day-01 and Day-28) on unbound concentration of Saroglitazar in systemic circulation following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function

  The blood samples will be collected on Day 1 and Day 28 at pre-dose, 2.0 h and 24.0 h post dose.

• To evaluate the trough plasma concentration of Saroglitazar (parent compound)

  To evaluate the trough plasma concentration of Saroglitazar following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function

  Trough plasma sample will be collected at pre-dose on Visit 3 (on day 8), Visit-4 (On day 15) and at Visit 5 (on day 22). Additional PK sample will be collected at 168.0 hours post dose of day 28 (i.e. on Day 35 ±3D)

• To determine the plasma PK of Saroglitazar (parent compound)

  The plasma concentration of Saroglitazar (parent compound) will be measured to estimate the Cmax following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.

  Serial PK blood samples will be collected on Day1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)

• To determine the plasma PK of Saroglitazar metabolite (Saroglitazar sulfoxide)

  The plasma concentration of Saroglitazar metabolite (Saroglitazar sulfoxide) will be measured to estimate the Cmax following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.

  Serial PK blood samples will be collected on Day 1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)

Study Arms (2)

Saroglitazar Magnesium 1 mg

EXPERIMENTAL

The study drug will be administered from Day 1 to Day 28 once daily in the morning before breakfast without food. Study drug -Saroglitazar Magnesium tablets; Dosage form- Tablets (immediate release); Dose- 1 mg/day; Frequency- One tablet per day (in the morning before breakfast without food); Duration of treatment- 28 consecutive days

Drug: Saroglitazar Magnesium 1 mg

Saroglitazar Magnesium 2 mg

EXPERIMENTAL

The study drug will be administered from Day 1 to Day 28 once daily in the morning before breakfast without food. Study drug -Saroglitazar Magnesium tablets: Dosage form- Tablets (immediate release); Dose- 2 mg/day; Frequency- One tablet per day (in the morning before breakfast without food); Duration- 28 consecutive days

Drug: Saroglitazar Magnesium 2 mg

Interventions

Saroglitazar Magnesium 1 mg DRUG

Group-8: Total of 18 subjects will be enrolled in the Group-8. Group 8A (n=6, consist of mild hepatic impairment subjects); Group 8B (n=6, consist of moderate hepatic impairment), Group 8C (n=3, consist of severe hepatic impairment and Group 8D (n=3, consist of control subjects with normal hepatic functions).

Also known as: Subjects will be domicile in clinic from Day -1 till Day 5 or Day 7 and from Day 27 through day 29 for PK sampling procedures.

Saroglitazar Magnesium 1 mg

Saroglitazar Magnesium 2 mg DRUG

Group-9: Total of 12 subjects will be enrolled in the Group-9. Group 9A (n=3, consist of mild hepatic impairment subjects); Group 9B (n=3, consist of moderate hepatic impairment), Group 9C (n=3, consist of severe hepatic impairment and Group 9D (n=3, consist of control subjects with normal hepatic functions).

Also known as: Subjects will be domicile in clinic from Day -1 till Day 5 or Day 7 and from Day 27 through day 29 for PK sampling procedures.

Saroglitazar Magnesium 2 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all subjects:
• Ability to comprehend and willingness to sign a written ICF for the study.
• Male or female aged 18 to 80 years (inclusive) at the time of signing the ICF.
• Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.
• Females must be non-pregnant, non-lactating and of non-childbearing potential or using highly efficient contraception for the full duration of the study.
• Females of child-bearing potential and males must agree to use contraception for the full duration of the study.
• Ability to swallow and retain oral medication.
• For Subjects in Groups 8 and 9 (Hepatic impairment group but with cirrhosis from cholestatic liver disease):
• Participants having documented history of hepatic impairment with cirrhosis due to cholestatic liver disease in Groups 8 and 9 will be classified in sub groups at screening based on CPT score. 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 hepatology Investigator.
• Laboratory test values for hepatic impairment subjects Groups 8 (8A, 8B, 8C) and 9 (9A, 9B, 9C) must be clinically acceptable to the Investigator and meet all the following parameters at Screening:
• ALT/AST value ≤ 10 × upper limit of normal (ULN)
• Absolute neutrophil count (ANC) ≥ 750/mm3
• Platelets ≥ 25,000/mm3
• Hemoglobin ≥ 8 g/dL
• α-fetoprotein \< 50 ng/mL or 50-80 ng/mL with negative imaging study (US, CT, MRI).

You may not qualify if:

• For all subjects:
• Any significant, unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the Investigator or designee.
• 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).
• History of stomach or intestinal surgery or resection within the six months prior to screening that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).
• History of any significant drug allergy (such as anaphylaxis) deemed clinically relevant by the Investigator.
• Any major surgery within 3 months of screening.
• Donation of blood or blood products within 3 months prior to screening.
• Current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment or symptoms of active infectious disease within the two weeks prior to screening.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 21 days prior to screening, unless deemed acceptable by the Investigator.
• Receiving or has received any investigational drug within the 30 days or 5 half-lives (whichever is longer), before receiving Saroglitazar Magnesium.
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2 by modification of diet in renal disease (MDRD) formula at screening.
• Positive alcohol breath test at the time of check-in or those subjects who have current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance or subject safety.
• Positive test for drugs of abuse at screening or admission. Subjects with a positive test based on a prescribed medication may be enrolled.
• Any subject with poor peripheral venous access
• Receipt of blood products within 1 month prior to check in.

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (1)

Zydus US002

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Fibrosis

Interventions

saroglitazar

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Deven V Parmar, MD, FCP

  Zydus Therapeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Farheen Shaikh

CONTACT

+1 6094534751; fshaikh@zydustherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Saroglitazar Magnesium at 1 mg and 2 mg single and once a daily multiple dose administration.

Study Record Dates

• First Submitted: July 25, 2021
• First Posted: September 16, 2021
• Study Start: October 21, 2021
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)