What side effects are associated with this type of intervention?

Common treatments for liver disease, such as pentoxifylline, cyclosporine, and ursodeoxycholic acid, have various side effects. Pentoxifylline can lower alanine and aspartate aminotransferase levels but does not significantly affect bilirubin or alkaline phosphatase levels. Cyclosporine may induce hair growth but is associated with serious adverse effects like liver enzyme elevation, pancreatitis, and bone marrow suppression, which often preclude long-term use. Ursodeoxycholic acid is generally well-tolerated but can cause mild gastrointestinal symptoms. These treatments highlight the importance of monitoring liver function and potential adverse effects during therapy.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of liver diseases, focusing on their pharmacokinetics and efficacy in patients with hepatic impairment. For instance, ursodeoxycholic acid has been approved for primary biliary cirrhosis, showing benefits in delaying disease progression and improving survival rates. Simeprevir and sofosbuvir, used in combination, have been approved for chronic hepatitis C, demonstrating high efficacy even in patients with compensated cirrhosis. While apalutamide is primarily used for prostate cancer, its pharmacokinetics in patients with severe hepatic impairment are being studied to understand its safety and efficacy in this population.

What other types of research exist?

Promising alternatives to Apalutamide for liver disease patients include enzalutamide and bicalutamide. Enzalutamide has shown efficacy and safety in patients with metastatic prostate cancer, and bicalutamide is another option, though its use should be carefully monitored due to potential hepatotoxicity. Consulting with a healthcare provider is essential to tailor the treatment to individual hepatic function and overall health status.

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Antiandrogen

Apalutamide for Liver Disease

Phase 1

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

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

Must have

Participants with normal hepatic function must have serum creatinine within normal limits and Creatinine Clearance (CrCL) greater than (>) 60 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) as calculated per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation

Participants with severe hepatic impairment must have a total Child-Pugh score of 10 to 15 inclusive, as determined by the investigator during screening and on Day -1 prior to study drug administration. Source documents to substantiate the clinical diagnosis (for example, ultrasonography, liver biopsy, liver/spleen scan, laboratory results or clinical findings), and medical history will be reviewed and signed by the investigator

Must not have

Participants with severe hepatic impairment previously diagnosed with hepatocellular carcinoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 78 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying how a prostate cancer medication, apalutamide, is processed in the bodies of people with severe liver problems compared to those with normal liver function. The goal is to understand any differences in how the drug is absorbed, distributed, metabolized, and excreted between these two groups. Apalutamide is a next-generation androgen receptor inhibitor approved for treatment of subjects with high-risk, non-metastatic, castration-resistant prostate cancer (NM-CRPC).

Who is the study for?

This trial is for adults with severe liver disease (Child-Pugh score 10-15) and normal kidney function, as well as healthy individuals with normal liver and kidney function. Those with severe mental impairment, thyroid issues, sexual dysfunction affecting men's health or active hepatitis are excluded.

What is being tested?

The study tests how a single dose of Apalutamide is processed by the body in people with severe liver damage compared to those with healthy livers. It aims to understand differences in drug behavior due to liver health.

What are the potential side effects?

While specific side effects for this trial aren't listed, common ones from Apalutamide may include fatigue, high blood pressure, rash, diarrhea, weight loss and fractures.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function is normal, with creatinine levels within the normal range.

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I have severe liver problems with a specific score.

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My kidney function is good, with a filtration rate of at least 45 mL/min.

Exclusion Criteria

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

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I have severe liver problems and was diagnosed with liver cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 78 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 78 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 78 days for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Area Under Concentration-time Curve from Time 0 to Infinite Time (AUC[0-infinity]) of Apalutamide

Area Under Concentration-time Curve from Time 0 to the Time of the Last Concentration (AUC[0-last]) of Apalutamide

Peak Plasma Concentration (Cmax) of Apalutamide

Secondary study objectives

Number of Participants with Adverse Event as a Measure of Safety and Tolerability

Side effects data

From 2021 Phase 2 trial • 86 Patients • NCT03279250

74%

Hot flashes

71%

Fatigue

44%

Anemia

38%

Hyperglycemia

26%

AST increase

26%

Hypertension

26%

Lipase increase

24%

ALT increase

24%

Dry skin

21%

Rash

18%

ACTH increase

18%

Cholesterol high

15%

Dizziness

15%

Amylase increase

12%

Memory impairment

12%

White blood cell decrease

12%

Constipation

12%

Lymphocyte count decrease

Myalgia

Paresthesia

Weight loss

Arthralgia

Hypothyrodism

LDH increase

Erectile dysfunction

Headache

Personality change

Dysgeusia

Dyspnea

HbA1c increased

Hypertriglyceridemia

Insomnia

Irritability

Anorexia

Atrial fibrillation

Anxiety

Bruising

Hypercalcemia

Dehydration

TSH increased

100%

80%

60%

40%

20%

Study treatment Arm

Arm B (LHRHa, Apalutamide, Abiraterone Acetate)

Arm A (LHRHa, Apalutamide)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Group 2: Participants with Normal Hepatic FunctionExperimental Treatment1 Intervention

Participants with normal hepatic function will receive single oral dose of apalutamide on Day 1 under fasted condition.

Group II: Group 1: Participants with Severe Hepatic ImpairmentExperimental Treatment1 Intervention

Participants with severe hepatic impairment will receive single oral dose of apalutamide on Day 1 under fasted condition.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Apalutamide

2015

Completed Phase 2

~5660

0 / 4Eligibility 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 liver disease include ursodeoxycholic acid (UDCA) and antiviral therapies. UDCA works by reducing the concentration of toxic bile acids, thereby protecting liver cells and slowing disease progression in conditions like primary biliary cirrhosis. Antiviral therapies, such as entecavir and tenofovir, inhibit viral replication in hepatitis B, reducing liver inflammation and preventing disease progression. Understanding the pharmacokinetics of drugs like apalutamide in patients with hepatic impairment is crucial, as liver function significantly affects drug metabolism and efficacy. This knowledge helps tailor treatments to ensure safety and effectiveness for liver disease patients.

Treatment of primary biliary cirrhosis with ursodeoxycholic acid combined with traditional Chinese medicine: A protocol for systematic review and meta analysis.Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.Influence of radioactive iodine therapy on liver function in patients with differentiated thyroid cancer.