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

Official title

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

Overview

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

Interventions

• Drug Saroglitazar Magnesium 1 mg
  Saroglitazar Magnesium 1 mg will be assigned to all participants enrolled in this open label study

Primary outcome measures

• Pharmacokinetics of Saroglitazar: Cmax [Time frame: 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 frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 (11)

• Number of participants with adverse events [Safety and Tolerability] [Time frame: From baseline to End of study (35 days)]
• Pharmacokinetics of Saroglitazar sulfoxide: Tmax [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: From baseline to end of treatment (29 days)]

Eligibility criteria

Inclusion criteria

• Male and/or female aged 18 to 80 years (both inclusive) at the time of signing the ICF.
• Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.
• Ability to swallow and retain oral medication.
• 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.
• 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)

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

Exclusion criteria

• Any significant or unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the investigator
• 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 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).
• The 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 of screening.
• Active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment or symptoms of active infectious disease within 2 weeks of screening.
• Receiving or has received any investigational drug within 30 days or 5 half-lives (whichever is longer), before receiving Saroglitazar Magnesium.
• Estimated glomerular filtration rate (<45 mL/min/1.73 m2 by CKD-EPI 2021 formula at screening.
• Any individual with poor peripheral venous access.
• Receipt of blood products within 1 month of check in.
• Human immunodeficiency virus type 1 antibody positive at screening.
• 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.
• 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.
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Zydus Site US001 — Indianapolis

Publications

• Vuppalanchi R, Cruz MM, Momin T, Shaikh F, Swint K, Patel H, Parmar D. Pharmacokinetic, Safety, and Pharmacodynamic Profiles of Saroglitazar Magnesium in Cholestatic Cirrhosis With Hepatic Impairment and Participants With Renal Impairment. Clin Pharmacol Ther. 2025 Jan;117(1):240-249. doi: 10.1002/cpt.3450. Epub 2024 Oct 2. PMID 39355940

Identifiers

NCT: NCT06825559 · SARO.24.003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗