Saroglitazar for Liver Cirrhosis

Recruiting at 1 trial location

Overseen By James Bainbridge, JD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Zydus Therapeutics Inc.

Must not be taking: Antibiotics, Antifungals, Antivirals, others

Disqualifiers: Malignancy, Surgery, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 36

Duration: 4 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial protocol suggests that participants may need to stop taking certain medications, especially those that could affect drug absorption, metabolism, or elimination. However, therapies for hepatic disease and associated disorders that have been stable for at least 30 days may be allowed, as well as some over-the-counter products approved by the Investigator.

What data supports the effectiveness of the drug Saroglitazar for liver cirrhosis?

Research shows that Saroglitazar, a drug that activates certain proteins in the body, has been effective in treating liver conditions like non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which can lead to liver cirrhosis. It has been shown to improve liver health in these conditions, suggesting potential benefits for liver cirrhosis as well. ^{1 2 3 4 5}

Is Saroglitazar safe for humans?

Saroglitazar has been found to be safe and well-tolerated in humans, including those with varying degrees of liver function, based on studies involving single doses and longer-term use for conditions like non-alcoholic fatty liver disease. ^{1 2 4 6 7}

What makes the drug Saroglitazar unique for treating liver cirrhosis?

Saroglitazar is unique because it is a dual PPAR-α/γ agonist, which means it activates specific proteins that help regulate fat metabolism and inflammation, potentially benefiting liver conditions like cirrhosis. It has shown promise in improving liver health in conditions like nonalcoholic fatty liver disease (NAFLD) and is being explored for its effects on liver cirrhosis. ^{1 2 3 8 9}

Research Team

Deven V Parmar, MD, FCP

Principal Investigator

Zydus Therapeutics Inc.

Eligibility Criteria

Adults aged 18-80 with cirrhosis due to cholestatic liver disease can join this trial. They must understand and sign consent, have a BMI of 18-48 kg/m2, and not be pregnant or breastfeeding. Participants need stable health, acceptable blood tests results (specific limits for liver enzymes, blood cells count), agree to use contraception, and cannot have other significant medical conditions or recent surgeries that could affect the study.

Inclusion Criteria

Ability to comprehend and willingness to sign a written ICF for the study

I have liver cirrhosis due to bile duct disease and my condition's severity may change.

I am in good health with no significant medical issues found during recent checks.

Exclusion Criteria

Human immunodeficiency virus (HIV) type 1 antibody positive at screening for all groups

My liver condition has changed significantly in the last month.

I frequently need fluid removed from my abdomen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saroglitazar Magnesium tablets once daily for 28 consecutive days

4 weeks

Daily administration with PK blood samples on Day 1 and Day 28

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

PK sample collection on Day 35 ±3 days

Open-label extension

Participants may continue receiving the study drug as part of the extension study

Treatment Details

Interventions

• Saroglitazar Magnesium

Trial Overview The trial is testing two doses of Saroglitazar Magnesium (1 mg and 2 mg) in people with hepatic impairment caused by cholestatic liver diseases. It's an open-label extension study where everyone knows which treatment they're getting.

Participant Groups

Group I: Saroglitazar Magnesium 2 mg Experimental Treatment 1 Intervention

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

Group II: Saroglitazar Magnesium 1 mg Experimental Treatment 1 Intervention

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

Saroglitazar Magnesium is already approved in India for the following indications:

Approved in India as Lipaglyn for:

• Type 2 diabetes mellitus
• Dyslipidemia
• Non-alcoholic fatty liver disease (NAFLD)
• Non-alcoholic steatohepatitis (NASH)

Who Is Running the Clinical Trial?

Zydus Therapeutics Inc.

Lead Sponsor

Trials

16

Recruited

1,100+

Findings from Research

In a Phase 1 study involving 55 subjects, saroglitazar magnesium was found to be safe and well tolerated across varying degrees of hepatic impairment, indicating its potential for treating liver conditions.

While mild and moderate hepatic impairment did not significantly affect the drug's pharmacokinetics, severe hepatic impairment led to a threefold increase in drug exposure, suggesting that careful monitoring or dose adjustments may be necessary for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. Lawitz, E., Parmar, D., Momin, T., et al.[2023]

In a study involving C57BL/6 mice, saroglitazar treatment significantly reduced liver injury markers and reversed liver fat accumulation, indicating its efficacy in addressing liver damage associated with NASH.

Importantly, saroglitazar completely prevented the development of liver tumors in treated mice, suggesting its potential as a chemopreventive agent against hepatocellular carcinoma in patients with fatty liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saroglitazar suppresses the hepatocellular carcinoma induced by intraperitoneal injection of diethylnitrosamine in C57BL/6 mice fed on choline deficient, l-amino acid- defined, high-fat diet. Giri, SR., Bhoi, B., Trivedi, C., et al.[2023]

In a study of 112 NAFLD patients treated with saroglitazar for 52 weeks, significant improvements were observed in liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) values, indicating enhanced liver health.

Saroglitazar also led to reductions in key biochemical markers such as ALT, AST, HbA1c, LDL, total cholesterol, and triglycerides, demonstrating its efficacy in managing NAFLD and diabetic dyslipidemia, with only mild side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of saroglitazar in real-world patients of non-alcoholic fatty liver disease with or without diabetes including compensated cirrhosis: A tertiary care center experience. Chaudhuri, S., Dutta, A., Chakraborty, SBD.[2023]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

Saroglitazar, a dual PPARα/γ agonist, effectively reduces liver inflammation, steatosis, and fibrosis in models of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), outperforming other treatments like pioglitazone and fenofibrate.

In mouse models, saroglitazar significantly improved liver function and reduced inflammatory and fibrosis biomarkers, indicating its potential as a superior therapeutic option for NASH compared to existing medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. Jain, MR., Giri, SR., Bhoi, B., et al.[2021]

In a study of 107 patients with diabetic dyslipidemia and non-alcoholic fatty liver disease, Saroglitazar significantly reduced liver enzymes (ALT and AST) and liver stiffness after 24 weeks of treatment, indicating improved liver health.

Saroglitazar also led to significant improvements in liver fat content and lipid parameters, suggesting it is an effective and safe therapeutic option for managing NAFLD in patients with diabetic dyslipidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: a prospective, observational, real world study. Goyal, O., Nohria, S., Goyal, P., et al.[2023]

Saroglitazar magnesium, a dual PPAR agonist, was found to be well tolerated in a study of 54 healthy adults, with only mild adverse events reported, indicating its safety for use.

While food intake reduced the maximum concentration (C max) of saroglitazar by 30%, it did not affect the overall absorption (AUC∞), suggesting that the drug's therapeutic efficacy remains intact regardless of food intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual PPARαγ Agonist, in Healthy Adult Subjects. Patel, MR., Kansagra, KA., Parikh, DP., et al.[2021]

In a phase 2A study involving liver transplant recipients with non-alcoholic fatty liver disease (NAFLD), saroglitazar treatment resulted in a significant reduction in liver fat, as measured by MRI, with 47% of patients showing a 30% reduction in fat content after 24 weeks.

Saroglitazar was well tolerated, showing no significant adverse effects on muscle mass or weight, although it did lead to a mild increase in visceral and subcutaneous fat, indicating a need for further research to fully understand its metabolic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients. Siddiqui, MS., Parmar, D., Shaikh, F., et al.[2023]

In a study of 91 overweight patients with nonalcoholic fatty liver disease (NAFLD), saroglitazar treatment for 3 months improved liver enzyme levels (transaminases) in all patients, indicating its efficacy in managing liver health.

However, significant improvements in liver stiffness and controlled attenuation parameter values were only observed in patients who achieved a weight reduction of at least 5%, highlighting the importance of weight loss in conjunction with saroglitazar therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saroglitazar for Nonalcoholic Fatty Liver Disease: A Single Centre Experience in 91 Patients. Padole, P., Arora, A., Sharma, P., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Saroglitazar suppresses the hepatocellular carcinoma induced by intraperitoneal injection of diethylnitrosamine in C57BL/6 mice fed on choline deficient, l-amino acid- defined, high-fat diet. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and safety of saroglitazar in real-world patients of non-alcoholic fatty liver disease with or without diabetes including compensated cirrhosis: A tertiary care center experience. [2023]

4. France pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: a prospective, observational, real world study. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual PPARαγ Agonist, in Healthy Adult Subjects. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients. [2023]

9. India pubmed.ncbi.nlm.nih.gov

Saroglitazar for Nonalcoholic Fatty Liver Disease: A Single Centre Experience in 91 Patients. [2023]