Saroglitazar Magnesium for Primary Biliary Cirrhosis

Recruiting at 45 trial locations

Overseen By Deven Parmar

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Zydus Therapeutics Inc.

Must not be taking: Thiazolidinediones, Fibrates, PPAR agonists, others

Disqualifiers: Liver diseases, Cirrhosis, Cardiovascular, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Open-Label Extension Study of Saroglitazar Magnesium in Participants With Primary Biliary Cholangitis

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as Thiazolidinediones, Fibrates, and other specific drugs, at least 12 weeks before screening. If you're on these medications, you may need to stop them before joining the trial.

Is Saroglitazar Magnesium safe for humans?

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

Research Team

Deven Parmar

Principal Investigator

Zydus Therapeutics Inc.

Eligibility Criteria

This trial is for individuals who have completed the SARO.21.001 study on primary biliary cholangitis and agreed to follow the protocol. They must not be heavy drinkers, have a MELD score under 15, or suffer from other liver diseases, unstable heart disease, uncontrolled thyroid issues, muscle diseases, or severe illnesses.

Inclusion Criteria

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

Participated and completed SARO.21.001, the double-blind treatment phase study

Exclusion Criteria

I have been drinking no more than the daily limit for my gender for the past 3 months.

Participants with MELD 3.0 score of 15 or greater

History or presence of other concomitant liver diseases at screening: Chronic hepatitis B or C virus (HBV, HCV) infection, Primary sclerosing cholangitis (PSC), Alcoholic liver disease, Autoimmune hepatitis (AIH)-PBC overlap syndrome, Hemochromatosis, Non-alcoholic steatohepatitis (NASH) on historical biopsy, Cirrhosis with complications, Use of Thiazolidinediones or Fibrates, Use of Obeticholic acid (OCA), methotrexate, budesonide and other systemic corticosteroids, History of bowel surgery, Unstable cardiovascular disease, An uncontrolled thyroid disorder, History of myopathies or evidence of active muscle disease, Abnormal laboratory values, Participation in another interventional clinical study, History of malignancy, Known allergy, sensitivity or intolerance to the study medication or formulation ingredients, Pregnancy-related exclusions, History or other evidence of severe illness or any other conditions that would make the participant unsuitable for the study, Cirrhosis with Child-Pugh-Turcotte (CPT) class B or C having score of 7 or above at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saroglitazar Magnesium 1 mg tablet orally once daily for 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension

Continuation of treatment to evaluate long-term safety and efficacy

24 months

Treatment Details

Interventions

• Saroglitazar Magnesium

Trial Overview The trial tests Saroglitazar Magnesium at a dose of 1 mg in patients with primary biliary cholangitis. It's an open-label extension which means everyone knows they're getting the actual drug and there's no placebo involved.

Participant Groups

Group I: 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 (24 months).

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 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]

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]