Obeticholic Acid + Bezafibrate for Primary Biliary Cirrhosis

Recruiting at 52 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Intercept Pharmaceuticals

Must be taking: Investigational product

Disqualifiers: Other liver diseases, Gallbladder disease, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 months

133 Participants Needed

Trial Summary

What is the purpose of this trial?

An Open Label Long-Term Study to Evaluate the Safety and Tolerability of the Fixed-Dose Combination (FDC) of Obeticholic Acid (OCA) and Bezafibrate (BZF) tablet in Subjects with Primary Biliary Cholangitis (PBC).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination of Obeticholic Acid and Bezafibrate for Primary Biliary Cirrhosis?

Research shows that combining obeticholic acid and fibrates can improve liver function tests in patients with primary biliary cholangitis who do not respond well to standard treatment. This suggests that the combination may be effective for primary biliary cirrhosis as well. ^{1 2 3 4 5}

Is the combination of obeticholic acid and bezafibrate safe for humans?

Obeticholic acid has been associated with serious liver-related side effects, especially in patients with advanced liver disease, and its use is restricted in such cases. The combination with fibrates, like bezafibrate, has shown some adverse events, but detailed safety data is limited outside of clinical trials. ^{1 2 3 5 6}

How is the drug combination of Obeticholic Acid and Bezafibrate unique for treating primary biliary cirrhosis?

The combination of Obeticholic Acid and Bezafibrate is unique because it targets patients with primary biliary cirrhosis who do not respond well to the standard treatment of ursodeoxycholic acid, offering a potential improvement in liver function tests. ^{2 3 4 5 7}

Research Team

Lynda Szczech, PhD

Principal Investigator

Intercept Pharmaceuticals Inc.

Eligibility Criteria

This trial is for individuals who have Primary Biliary Cholangitis (PBC) and are currently participating in either Study 747-213 or Study 747-214. It's designed to assess the long-term safety of a combined medication.

Inclusion Criteria

All subjects with PBC who participated and are actively taking investigational product in Study 747-213 or Study 747-214 are eligible to enroll in this study (977-311)

Exclusion Criteria

I have or had other liver diseases.

I have had liver failure or similar serious liver problems.

I am experiencing complications from primary biliary cholangitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fixed-dose combination of Obeticholic Acid and Bezafibrate once daily

Up to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive the study medication to evaluate long-term safety and tolerability

Long-term

Treatment Details

Interventions

• Fixed-Dose Combination of Obeticholic Acid and Bezafibrate

Trial Overview The study tests a fixed-dose combination tablet containing Obeticholic Acid (5 mg) and Bezafibrate (400 mg). The goal is to understand how safe and tolerable this medication is over an extended period for PBC patients.

Participant Groups

Group I: OCA 5 mg + BZF 400 mg SR Experimental Treatment 1 Intervention

Participants will be administered with OCA 5 mg + BZF 400 mg SR once daily.

Who Is Running the Clinical Trial?

Intercept Pharmaceuticals

Lead Sponsor

Trials

29

Recruited

16,600+

Findings from Research

The multicentric observational study compared the effects of obeticholic acid and fibrates in patients with primary biliary cholangitis, highlighting their efficacy in managing this liver disease.

Results indicated that obeticholic acid may provide superior benefits in improving liver function tests compared to fibrates, suggesting it could be a more effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing Medical Education Questions: November 2021. Richter, SJ.[2023]

In a study of 351 patients with primary biliary cholangitis, treatment with obeticholic acid (OCA) or fibrates significantly improved liver enzyme levels and the GLOBE score, indicating better liver health.

Adverse events occurred in 14.7% of patients, with the most common being pruritus, and treatment discontinuation was more frequent with fenofibrate due to intolerance, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study. Reig, A., Álvarez-Navascués, C., Vergara, M., et al.[2021]

Obeticholic acid (OCA) significantly reduced alkaline phosphatase (ALP) levels in patients with primary biliary cirrhosis who did not respond adequately to ursodeoxycholic acid, with reductions of 21%-25% compared to only 3% in the placebo group over 3 months.

The treatment was effective across all doses (10 mg, 25 mg, and 50 mg), but the 10 mg dose had the lowest incidence of pruritus, a common side effect, while maintaining significant biochemical improvements, which were sustained in a 12-month extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Hirschfield, GM., Mason, A., Luketic, V., et al.[2022]

In a study of 100 cirrhotic patients with primary biliary cholangitis (PBC) treated with obeticholic acid (OCA), only about one-third achieved a biochemical response after 6 and 12 months, indicating limited efficacy in this population.

Key risk factors for serious adverse events (SAEs) during OCA therapy included high bilirubin levels (≥1.4 mg/dl), lower albumin levels, and a higher Child-Pugh score, suggesting that careful baseline assessments are essential to identify patients who may not safely benefit from OCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid. De Vincentis, A., D'Amato, D., Cristoferi, L., et al.[2023]

References

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

Continuing Medical Education Questions: November 2021. [2023]

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

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Determinants of the effectiveness of bezafibrate combined with ursodeoxycholic acid in patients with primary biliary cholangitis. [2023]

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

Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. [2022]

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

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Combination therapy of bezafibrate and ursodeoxycholic acid for primary biliary cirrhosis: A meta-analysis. [2020]