What is the mechanism of action of this treatment?

Common treatments for itching work through various mechanisms to address the underlying causes. Linerixibat, for example, inhibits the ileal bile acid transporter, reducing bile acid reabsorption and levels in the body, which is crucial for patients with cholestatic pruritus. Antihistamines block histamine receptors to mitigate allergic reactions, while corticosteroids reduce inflammation and immune responses. Understanding these mechanisms is essential for selecting the most effective treatment based on the specific cause of the itching, thereby improving patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for cholestatic pruritus include bile acid resins like cholestyramine, rifampin, and opioid antagonists such as naltrexone. Bile acid resins can cause constipation, fat malabsorption, and vitamin K deficiency, necessitating monitoring for these deficiencies. Rifampin may lead to hepatotoxicity and drug interactions. Opioid antagonists can induce opioid withdrawal-like symptoms and pain. These side effects highlight the need for careful management and monitoring during treatment.

What prior FDA approvals exist?

FDA-approved treatments for itching, particularly those related to bile acid transport, include bile acid sequestrants like cholestyramine, which is used to treat pruritus associated with cholestasis. Additionally, opioid antagonists such as naltrexone have been approved for pruritus in various conditions, including cholestasis. These treatments work by different mechanisms but are aimed at reducing the sensation of itch in patients with underlying liver conditions. While Linerixibat is still under study, these existing treatments provide a framework for managing pruritus through modulation of bile acids and opioid receptors.

What other types of research exist?

Promising novel alternatives to Linerixibat for treating itching in 2024 include systemic μ-opioid receptor antagonists such as naltrexone, kappa opioid receptor agonists, and selective serotonin reuptake inhibitors (SSRIs) like sertraline and paroxetine. These treatments have demonstrated efficacy in managing pruritus in various conditions.

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Bile Acid Sequestrant

Linerixibat for Itching in Cholangitis

Phase 3

Waitlist Available

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants who have moderate to severe itch

Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.

Must not have

Current symptomatic cholelithiasis or cholecystitis.

History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 weeks

Awards & highlights

Pivotal Trial

Summary

This trial is testing a medication called linerixibat to see if it can help reduce severe itching in people with a liver condition called Primary Biliary Cholangitis (PBC). The study will compare the effects of linerixibat to check its effectiveness and safety.

Who is the study for?

This trial is for adults aged 18-80 with Primary Biliary Cholangitis (PBC) who suffer from moderate to severe itching. Candidates must have documented PBC and cannot have certain liver complications, changes in itch medication within the last 8 weeks, primary sleep disorders, or active viral infections among other exclusions.

What is being tested?

The GLISTEN study is testing the effectiveness and safety of a drug called Linerixibat against a placebo in relieving itch caused by PBC. It also looks at how this treatment affects patients' quality of life.

What are the potential side effects?

While specific side effects are not listed here, potential risks may include typical drug reactions such as gastrointestinal issues, skin reactions, or abnormal blood tests reflecting liver function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I experience moderate to severe itching.

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I am between 18 and 80 years old.

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I experience moderate to severe itching.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently experiencing symptoms of gallstones or gallbladder inflammation.

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I have had serious liver problems like bleeding, confusion, or fluid in the abdomen.

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I plan to undergo treatments for itchiness caused by bile blockage.

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I do not have active hepatitis, liver cancer, or diseases caused by alcohol.

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I haven't taken obeticholic acid in the last 8 weeks.

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I have a skin condition like eczema or psoriasis that causes itching.

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I have or had colorectal cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline in Monthly Itch Scores over 24 weeks using Numerical Rating Scale (NRS)

Secondary study objectives

Change from Baseline in Monthly Sleep Score as measured by NRS over 24 weeks

Change from Baseline in Patient's Global Impression of Severity (PGI-S) over 24 weeks

Change from Baseline in Primary Biliary Cholangitis-40 (PBC-40) domain scores at Week 24

+7 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Participants receiving placebo followed by linerixibatExperimental Treatment2 Interventions

Group II: Participants receiving linerixibat followed by placeboExperimental Treatment2 Interventions

Group III: Participants receiving linerixibatExperimental Treatment1 Intervention

Group IV: Participants receiving placeboPlacebo Group1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Linerixibat

2022

Completed Phase 1

~60

Placebo

1995

Completed Phase 3

~2670

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for itching work through various mechanisms to address the underlying causes. Linerixibat, for example, inhibits the ileal bile acid transporter, reducing bile acid reabsorption and levels in the body, which is crucial for patients with cholestatic pruritus. Antihistamines block histamine receptors to mitigate allergic reactions, while corticosteroids reduce inflammation and immune responses. Understanding these mechanisms is essential for selecting the most effective treatment based on the specific cause of the itching, thereby improving patient outcomes.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial.