Saroglitazar Magnesium for Primary Biliary Cholangitis

(EPICS-III Trial)

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

186 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests Saroglitazar Magnesium tablets on patients with Primary Biliary Cholangitis to see if it can help their liver work better and reduce inflammation.

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 Saroglitazar Magnesium safe for humans?

Saroglitazar Magnesium has been found to be safe and well-tolerated in studies involving patients with liver conditions, including those with varying degrees of liver impairment. However, individuals with severe liver impairment may need close monitoring or dose adjustments. ^{1 2 3 4 5}

What makes Saroglitazar Magnesium unique for treating primary biliary cholangitis?

Saroglitazar Magnesium is unique because it acts as a dual PPAR (peroxisome proliferator-activated receptor) agonist, which may help address both liver inflammation and lipid abnormalities in primary biliary cholangitis, offering a novel approach compared to standard treatments like ursodeoxycholic acid and obeticholic acid. ^{6 7 8 9 10}

Research Team

Deven V Parmar, MD

Principal Investigator

Zydus Therapeutics Inc.

Eligibility Criteria

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 no health issues that would interfere with Saroglitazar Magnesium treatment.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

References

1. United States 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis. [2022]

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

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. [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. India pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2022]

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

Work in Progress: Drugs in Development. [2019]

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

Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis. [2022]

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

Experimental Pharmacological Agents for the Treatment of Primary Biliary Cholangitis. [2020]