Saroglitazar Magnesium for Primary Biliary Cholangitis

(EPICS-III Trial)

Not currently recruiting at 60 trial locations

Overseen By Farheen Shaikh

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Zydus Therapeutics Inc.

Must be taking: Ursodeoxycholic acid

Must not be taking: Thiazolidinediones, Fibrates, Obeticholic acid, others

Disqualifiers: Chronic hepatitis B or C, Cirrhosis, Unstable cardiovascular disease, Uncontrolled thyroid disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Saroglitazar Magnesium tablets as a potential treatment for Primary Biliary Cholangitis (PBC), a liver disease that damages bile ducts. Researchers aim to determine if daily doses of 1 mg or 2 mg can improve symptoms. Participants will receive either the study drug or a placebo (a pill with no active ingredients). Those diagnosed with PBC who have struggled with liver enzyme problems despite treatment might be suitable candidates.

As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for improved management of PBC.

Will I have to stop taking my current medications?

The trial requires that you have not used certain medications like thiazolidinediones, fibrates, obeticholic acid, and some others for at least 12 weeks before starting. If you are on ursodeoxycholic acid (UDCA), you must have been on a stable dose for at least 6 months before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Saroglitazar Magnesium is generally safe for patients. Studies have found that taking 2 mg or 4 mg daily can improve liver enzyme levels, a positive outcome. Importantly, side effects were similar across different groups, indicating the medication's safety. These results are promising for those considering participation in a clinical trial for Saroglitazar Magnesium to treat Primary Biliary Cholangitis (PBC). ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Saroglitazar Magnesium is unique because it targets PPAR alpha and gamma receptors, which play a role in reducing inflammation and bile acid build-up in the liver, a new approach for treating Primary Biliary Cholangitis (PBC). Unlike standard treatments like ursodeoxycholic acid (UDCA) and obeticholic acid, which primarily focus on bile acid modification, Saroglitazar Magnesium offers a dual-action mechanism that may provide additional benefits in managing liver inflammation and fibrosis. Researchers are excited about this treatment because its novel mechanism could improve liver function and offer a new hope for patients who do not fully respond to existing therapies.

What evidence suggests that this trial's treatments could be effective for Primary Biliary Cholangitis?

Research has shown that Saroglitazar Magnesium may help treat Primary Biliary Cholangitis (PBC). In this trial, participants will receive either Saroglitazar Magnesium or a placebo. Studies have found that patients taking Saroglitazar Magnesium experienced about a 50% reduction in alkaline phosphatase (ALP) levels, which are important for liver health. Saroglitazar is unique because it works in two ways to improve liver enzyme levels and cholesterol. Positive results from earlier trials suggest it could be an effective treatment option for PBC. ^{1 3 4 5 6}

Who Is on the Research Team?

Deven V Parmar, MD

Principal Investigator

Zydus Therapeutics Inc.

Are You a Good Fit for This Trial?

Adults aged 18-75 with Primary Biliary Cholangitis (PBC) are eligible for this trial. They must have had elevated liver enzyme levels for at least 6 months and either be on a stable dose of Ursodeoxycholic acid or unable to tolerate it. A confirmed PBC diagnosis according to specific guidelines is required, but those with other liver diseases, certain medical conditions, or recent participation in another clinical study cannot join.

Inclusion Criteria

You have been diagnosed with Primary Biliary Cirrhosis

Exclusion Criteria

I do not have unstable heart conditions.

I have been drinking up to 2 drinks a day if male, or 1 if female, for the last 3 months.

I have not had a stroke or mini-stroke in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saroglitazar Magnesium 1 mg or 2 mg, or placebo, orally once daily for 52 weeks

52 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Saroglitazar Magnesium

Trial Overview The trial is testing Saroglitazar Magnesium tablets at two different doses (1 mg and 2 mg) against a placebo to treat patients with PBC. The goal is to see if these tablets can help manage the condition better than not taking them.

How Is the Trial Designed?

Group I: Saroglitazar Magnesium 2 mg Experimental Treatment 2 Interventions

Subjects who received Saroglitazar Magnesium 2 mg tablet orally administered once daily in the morning before breakfast are switched to Saroglitazar Magnesium 1 mg for remaining of the treatment period

Group II: Saroglitazar Magnesium 1 mg Experimental Treatment 1 Intervention

Saroglitazar Magnesium 1 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (52 weeks).

Group III: Placebo Placebo Group 1 Intervention

Placebo tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment (52 weeks).

Who Is Running the Clinical Trial?

Zydus Therapeutics Inc.

Lead Sponsor

Trials

16

Recruited

1,100+

Published Research Related to This Trial

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 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]

In a phase II trial involving 37 patients with primary biliary cholangitis (PBC), saroglitazar significantly reduced alkaline phosphatase (ALP) levels after 16 weeks, with reductions of 49% and 51% for the 4 mg and 2 mg doses, respectively, compared to only 3% in the placebo group.

While saroglitazar was generally well-tolerated, there was a higher incidence of elevated liver enzymes in the 4 mg group, leading to further studies at lower doses (2 mg and 1 mg) to ensure safety while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis. Vuppalanchi, R., Caldwell, SH., Pyrsopoulos, N., et al.[2022]

Current treatments for primary biliary cholangitis, such as ursodeoxycholic acid and obeticholic acid, are not effective for all patients, highlighting the need for new therapies.

The review discusses various promising drug candidates in development that target different biological pathways, including the farnesoid X receptor and immunological agents, which may offer new options for managing this autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Work in Progress: Drugs in Development. Webb, GJ., Hirschfield, GM.[2019]

In a phase 2a trial involving 22 patients with primary biliary cholangitis, the drug GSK2330672 was found to be safe and effective in significantly reducing pruritus (itch) severity over 14 days, with a 57% reduction in itch scores on a numerical rating scale.

While GSK2330672 showed promising results in alleviating itch and reducing serum bile acids, the most common side effect was diarrhea, which could limit its long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Hegade, VS., Kendrick, SF., Dobbins, RL., et al.[2022]

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 16-week study involving 7 female patients with primary biliary cholangitis (PBC), treatment with saroglitazar led to a significant reduction in alkaline phosphatase (ALP) levels by 48% from baseline, indicating its efficacy in improving liver function.

Saroglitazar was well-tolerated and resulted in rapid improvements in ALP levels as early as week 4, suggesting it may be a promising treatment option for PBC patients who do not respond to standard therapy with ursodeoxycholic acid (UDCA).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis. Vuppalanchi, R., González-Huezo, MS., Payan-Olivas, R., et al.[2023]

Citations

1. 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 ...

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

NCT03112681 | Study to Evaluate Safety, Tolerability and ... Effect of a 16-week Treatment Regimen of Saroglitazar Magnesium 2 mg and 4 mg on Alkaline Phosphatase (ALP) Levels in Patients With Primary Biliary Cholangitis.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8191832/

Results of a Phase 2, Prospective, Multicenter ... The researchers concluded that saroglitazar magnesium resulted in an estimated 50% decrease in ALP levels, with the reduction sustained, and that it had an ...

4. zyduslife.com zyduslife.com/investor/admin/uploads/21/83/Zydus-Therapeutics-Reports-Positive-Topline-Results-from-EPICS-III-Phase-2(b)-3-Trial-of-Saroglitazar-Magnesium-in-Patients-with-Primary-Biliary-Cholangitis.pdf

Zydus Therapeutics Reports Positive Topline Results from ... Saroglitazar is the first PPAR alpha/gamma agonist to demonstrate positive Phase 3 data in patients with PBC and has the potential to bring real ...

5. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/SARO-23-002

Saroglitazar Magnesium in Primary Biliary Cholangitis The purpose of this study is to evaluate the effectiveness (improvement in liver enzymes and lipid profiles) and safety (side effects) of an experimental.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34487750/

Proof-of-concept study to evaluate the safety and efficacy ... Conclusions: Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are ...