Apalutamide for Liver Disease

No longer recruiting at 6 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Thyroid hormones

Disqualifiers: Sexual dysfunction, Hepatitis A/B/C, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the drug apalutamide (Erleada) behaves in the body of individuals with severe liver problems compared to those with normal liver function. The goal is to understand the drug's processing, aiding in the development of treatments for liver conditions. It involves two groups: one with severe liver issues and another with healthy livers. Suitable participants either have serious liver impairment without severe confusion or are healthy without liver problems. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to contribute to foundational knowledge about apalutamide.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications, but you cannot use thyroid hormone replacement therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use thyroid hormone replacement therapy.

Is there any evidence suggesting that apalutamide is likely to be safe for humans?

Research has shown that apalutamide is usually well-tolerated. Studies have not linked it to serious liver problems such as sudden liver failure or long-term hepatitis. Specifically, in patients with mild to moderate liver issues, apalutamide did not significantly affect how the body absorbed or processed the drug. However, limited information exists on its effects in people with severe liver problems. This study aims to explore that further. Although apalutamide is approved for other uses, individuals with severe liver conditions should exercise caution until more evidence becomes available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Apalutamide is unique because, unlike standard treatments for liver disease, which often focus on managing symptoms or slowing disease progression, it is primarily used for prostate cancer and works by blocking the action of androgens, which are male hormones that can promote tumor growth. Researchers are excited about its potential in liver disease because it could offer a novel mechanism of action by interfering with pathways that are not typically targeted in liver disease management. This could lead to new insights into how liver conditions might be managed differently, potentially providing more effective treatment options for patients with severe hepatic impairment.

What evidence suggests that apalutamide might be an effective treatment for liver disease?

Research has shown that apalutamide helps treat prostate cancer by improving survival rates when combined with other treatments. However, its effects on liver disease remain unclear. This trial will study apalutamide in two groups: participants with severe hepatic impairment and those with normal hepatic function. Since the liver processes apalutamide, its effects might differ in individuals with liver problems. No direct evidence currently supports its efficacy for liver disease, but researchers are examining its impact on liver function. The treatment has not been linked to serious liver issues, such as sudden liver failure. Current research focuses on understanding how the drug works in individuals with liver problems. ^{1 2 3 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

My liver functions normally and I am in good health.

I have severe liver problems with a specific score.

Exclusion Criteria

Any participant with screening thyroid stimulating hormone (TSH) level > upper limit of normal (ULN)

I have normal liver function and may have been exposed to Hepatitis A, B, or C.

I have normal liver function but experience sexual dysfunction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of apalutamide on Day 1 under fasted conditions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

11 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide

Trial Overview 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.

How Is the Trial Designed?

Group I: Group 2: Participants with Normal Hepatic Function Experimental Treatment 1 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 Impairment Experimental Treatment 1 Intervention

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

Apalutamide is already approved in United States, European Union for the following indications:

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Gemcabene, a drug initially developed for dyslipidemia, showed significant anti-inflammatory and lipid-lowering effects in a preclinical model of NASH, indicating its potential utility in treating this liver disease.

In mice with NASH, gemcabene reduced key markers of inflammation and fibrosis, which are critical for preventing disease progression, suggesting it could be an effective treatment option for patients with NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH. Oniciu, DC., Hashiguchi, T., Shibazaki, Y., et al.[2018]

In a study involving nine patients with asymptomatic primary biliary cirrhosis (aPBC) who did not fully respond to ursodeoxycholic acid (UDCA), fenofibrate treatment for twelve weeks significantly reduced serum levels of alkaline phosphatase and immunoglobulin M, indicating improved liver function and immune response.

Fenofibrate was well-tolerated with no adverse reactions reported, suggesting it is a safe addition to UDCA therapy for patients with aPBC, potentially enhancing treatment efficacy through its anti-inflammatory and immunomodulatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate for patients with asymptomatic primary biliary cirrhosis. Dohmen, K., Mizuta, T., Nakamuta, M., et al.[2021]

The combination of ursodeoxycholic acid (UDCA) with rosuvastatin (RSV) and ezetimibe (EZE) significantly reduced liver damage markers, collagen accumulation, and fibrosis in various NAFLD mouse models, indicating its potential efficacy in treating the disease.

This combination therapy not only decreased serum alanine aminotransferase (ALT) levels and apoptosis in liver cells but also improved cell survival, suggesting a promising new strategy for inhibiting the progression of non-alcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model. Seo, SH., Lee, DH., Lee, YS., et al.[2022]

In a pooled analysis of three Phase 3 studies involving 1,035 patients treated with sofosbuvir/velpatasvir (SOF/VEL) for hepatitis C, the safety profile was comparable to that of placebo, with similar rates of treatment-emergent adverse events (TEAEs) at 79.4% for SOF/VEL and 76.7% for placebo.

The majority of TEAEs were mild to moderate, and serious adverse events were rare (2.2%), with none leading to study discontinuation or being related to the treatment, indicating that SOF/VEL is a well-tolerated option for HCV treatment, regardless of factors like age or liver condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tolerability of sofosbuvir/velpatasvir for 12 weeks in patients treated in the ASTRAL 1, 2 and 3 studies: A pooled safety analysis. Jacobson, IM., Bourgeois, S., Mathurin, P., et al.[2023]

In a study of 1880 patients with chronic hepatitis C in Taiwan, the treatment with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks resulted in a high sustained virologic response (SVR12) rate of 95.6%, indicating its effectiveness in clearing the virus.

The treatment was well-tolerated, with only 0.2% of patients discontinuing due to adverse events, and serious adverse events were not related to the medication, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan. Liu, CH., Chen, PY., Chen, JJ., et al.[2021]

In a phase 3 study, seladelpar (10 mg) significantly improved liver biochemistry in patients with primary biliary cholangitis (PBC) who did not respond well to standard treatment, with 78.2% of patients meeting the primary efficacy endpoint compared to only 12.5% in the placebo group.

Seladelpar also effectively reduced pruritus (itching) and showed a good safety profile, with no serious treatment-related adverse events reported, indicating it is a well-tolerated option for patients with PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hirschfield, GM., Shiffman, ML., Gulamhusein, A., et al.[2023]

In a study of 132 NAFLD patients treated with pemafibrate for at least 24 weeks, significant reductions in liver enzymes (ALT decreased from 81.0 IU/L to 48.0 IU/L) and triglyceride levels were observed, indicating improved liver function.

Pemafibrate also reduced liver stiffness, as measured by shear wave velocity, from 1.45 m/s to 1.32 m/s over 48 weeks, suggesting it may be an effective treatment for NAFLD, particularly in patients with elevated triglycerides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pemafibrate on liver enzymes and shear wave velocity in non-alcoholic fatty liver disease patients. Sugimoto, R., Iwasa, M., Eguchi, A., et al.[2023]

In a study of 196 patients with chronic hepatitis C treated with sofosbuvir and ribavirin, common side effects included fatigue (55%), fever (42%), myalgias (44.2%), and nausea (50%), indicating that while side effects are present, they are generally manageable.

Sofosbuvir was associated with fewer severe adverse effects compared to previous treatments, with only 3% of patients experiencing absolute neutropenia and 5% moderate to severe thrombocytopenia, although careful monitoring is essential for patients with decompensated liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir Adverse Events Profile in a Subset of Pakistani Population. Iqbal, S., Yousuf, MH., Raza, A., et al.[2018]

In a 72-week study involving 48 patients with nonalcoholic steatohepatitis (NASH), apararenone 10 mg/day demonstrated significant improvements in liver fibrosis markers compared to placebo, indicating its potential efficacy in treating this condition.

Apararenone was found to be safe and well-tolerated, with similar rates of adverse drug reactions as the placebo group, although it did cause a temporary increase in serum potassium levels that returned to baseline after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apararenone (MT-3995) in patients with nonalcoholic steatohepatitis: A randomized controlled study. Okanoue, T., Sakamoto, M., Harada, K., et al.[2021]

In a study of 100 type 2 diabetes patients, pioglitazone significantly reduced HbA1c levels and liver enzymes (AST and ALT) in patients with alcoholic fatty liver disease (AFLD) after 3 months of treatment, indicating its potential efficacy for this condition.

The treatment was effective even at low doses (≤ 7.5 mg/day), suggesting that pioglitazone could be a safe and effective option for managing liver dysfunction in T2D patients with AFLD, similar to its effects in those with non-alcoholic fatty liver disease (NAFLD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of 3 months of additional pioglitazone treatment in type 2 diabetes patients with alcoholic fatty liver disease. Asakawa, M., Takagi, N., Hamada, D., et al.[2023]

The DANBIO database captured 20 times more adverse events related to biological agents than the Danish Medicines Agency, highlighting its effectiveness in monitoring patient safety.

Infections and hypersensitivity reactions were the most common adverse events, with older age, longer disease duration, and a higher number of previous DMARD treatments identified as risk factors for bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO). Hetland, ML., Unkerskov, J., Ravn, T., et al.[2019]

Rilpivirine has been shown to have a lower incidence and severity of neuropsychiatric side effects compared to efavirenz, based on data from 1,728 patients across multiple clinical trials.

Patients treated with rilpivirine also exhibited a better lipid profile and fewer cases of subclinical transaminase elevation, although safety data in patients with advanced liver failure or those coinfected with hepatitis B or C is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety profile of rilpivirine: general and neuropsychiatric tolerability, safety in patients with hepatitis B or C viruses, and lipid profile]. López Cortés, LF., Martínez, E., von Wichmann, MÁ.[2016]

Citations

1. jnjmedicalconnect.com jnjmedicalconnect.com/products/erleada/medical-content/use-of-erleada-in-patients-with-hepatic-impairment

Use of ERLEADA in Patients with Hepatic Impairment A summary of clinical data regarding ERLEADA® (apalutamide) use in patients with hepatic impairment.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK547950/

Apalutamide - LiverTox - NCBI Bookshelf - NIH Outcome and Management​​ Apalutamide has not been linked to cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome. ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04154774

A Study of Apalutamide in Participants With Severe Hepatic ... The purpose of this study is to characterize the single-dose pharmacokinetic (PK) of apalutamide in participants with severe hepatic impairment relative to ...

4. ema.europa.eu ema.europa.eu/en/documents/product-information/erleada-epar-product-information_en.pdf

Erleada, INN - apalutamide - EMA Erleada is not recommended in patients with severe hepatic impairment as there are no data in this patient population and apalutamide is primarily hepatically ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10692265/

Role of apalutamide in the treatment landscape for patients ... At the first interim analysis of TITAN data, with a median follow-up of 22.7 months, apalutamide in combination with ADT significantly improved ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/210951orig1s000multidiscipliner.pdf

210951Orig1s000 - accessdata.fda.gov with normal hepatic function. The unbound fraction of apalutamide or N-desmethyl apalutamide was not affected by hepatic impairment. The ...