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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new treatment called Saroglitazar Magnesium for individuals with liver cirrhosis caused by cholestatic liver disease. The goal is to assess the drug's impact on liver function and overall health. Participants will take either a 1 mg or 2 mg dose daily for 28 days. The trial seeks individuals with liver cirrhosis linked to cholestatic liver disease who have managed this condition for some time. Those with liver issues due to other causes, such as viral hepatitis, may not be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that Saroglitazar Magnesium is likely to be safe for humans?

Research has shown that Saroglitazar Magnesium is generally safe for people with liver conditions. Studies have found that both 1 mg and 2 mg doses are safe and well-tolerated in individuals with liver issues, including those with mild liver problems. Importantly, these studies revealed no major safety concerns.

Saroglitazar Magnesium has been used in people with various liver conditions and has improved liver health markers without significant side effects. This suggests it is a safe option for many patients, although individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Saroglitazar Magnesium for liver cirrhosis because it offers a potentially novel approach by targeting the PPAR (peroxisome proliferator-activated receptor) pathway, which is different from many standard treatments that primarily focus on managing symptoms or complications. Unlike other treatments that may take longer to show effects, Saroglitazar Magnesium has the potential to provide results within just 28 days. Additionally, it is administered orally once a day, which is convenient compared to some existing treatments that may require more frequent dosing or invasive administration methods. This combination of a new mechanism, faster action, and ease of use has researchers hopeful about its impact on liver health.

What evidence suggests that Saroglitazar Magnesium might be an effective treatment for liver cirrhosis?

Research has shown that Saroglitazar Magnesium may improve liver health. In earlier studies, patients experienced significant improvements in liver stiffness, a measure of liver damage, over 24 to 52 weeks. Saroglitazar also positively affected liver enzyme levels, which are crucial for assessing liver function. It has benefited patients with primary biliary cholangitis, a type of liver disease, by enhancing liver function and overall health. The treatment regulates fat and sugar levels in the body, potentially reducing stress on the liver. Overall, early results suggest Saroglitazar could be effective for liver conditions, including those related to cirrhosis. Participants in this trial will receive either a 1 mg or 2 mg dose of Saroglitazar Magnesium to evaluate its effects on liver cirrhosis. ^{1 6 7 8 9}

Who Is on the Research Team?

Deven V Parmar, MD, FCP

Principal Investigator

Zydus Therapeutics Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10037031/

Efficacy and safety of saroglitazar in real‐world patients ... There was significant improvement of LSM from baseline (11.03 ± 7.19 kPa) to 24‐week (9.29 ± 6.39 kPa) and 52‐week (8.59 ± 6.35 kPa) values respectively.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03112681

NCT03112681 | Study to Evaluate Safety, Tolerability and ... The primary objective is to investigate the effect of a 16-week treatment regimen of Saroglitazar magnesium 2 mg and 4 mg on alkaline phosphatase (ALP) levels ...

3. gastroenterologyadvisor.com gastroenterologyadvisor.com/news/saroglitizar-demonstrates-efficacy-in-primary-biliary-cholangitis/

Saroglitazar Demonstrates Efficacy in Primary Biliary ... “Saroglitazar is the first PPAR alpha/gamma agonist to demonstrate positive phase 3 data in patients with PBC and has the potential to bring ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12395119/

Evaluation of Effectiveness and Tolerability of Saroglitazar in ... Saroglitazar demonstrated significant improvements in glycemic control, lipid profile, and liver enzymes with a favorable safety profile in ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2210740123000992

Effects of saroglitazar in the treatment of non-alcoholic fatty ... In this systematic review and meta-analysis, we found that treatment with adjunct 4 mg saroglitazar for 12–52 weeks showed improvements in liver function and ...

6. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3450?af=R

Pharmacokinetic, Safety, and Pharmacodynamic Profiles of ... Saroglitazar (1 and 2 mg) was safe and well-tolerated in cholestatic cirrhosis with mild HI and participants with severe RI without major PK changes.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06825559

NCT06825559 | Evaluate PK & Safety of Saroglitazar in ... A phase 1, open-label, single arm study to evaluate pharmacokinetics, safety, and tolerability of Saroglitazar Magnesium dosed on alternate days.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03112681

NCT03112681 | Study to Evaluate Safety, Tolerability and ... Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Mg in Patients With Primary Biliary Cholangitis (EPICS). ClinicalTrials.gov ID NCT03112681.

9. nature.com nature.com/articles/s41598-020-78342-x

Saroglitazar in patients with non-alcoholic fatty liver ... We conclude that Saroglitazar leads to significant improvement in transaminases, LSM, and CAP in NAFLD patients with DD.