A Study Evaluating How Moderate Liver Impairment Affects the Absorption, Distribution, Metabolism, and Elimination of Sevabertinib After a Single Oral Dose

NCT ID: NCT07102095

Last Updated: 2025-08-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-24
• Study Completion Date: 2026-01-23

Brief Summary

This is a research study to understand how liver impairment affects the way the body processes a new cancer medicine called sevabertinib (BAY 2927088).

Sevabertinib is an experimental drug being developed to treat certain types of cancers that have specific genetic changes called HER2 mutations. This includes lung cancer, tumors that have spread to other parts of the body (metastatic), and tumors that cannot be removed with surgery (unresectable). Before this medicine can be given to cancer patients with liver problems, researchers need to understand how liver disease might change the way the body handles the drug.

The study will include about 20 people divided into two groups: 10 people with moderate liver problems (called Child-Pugh B liver impairment) and 10 healthy people with normal liver function. The healthy volunteers will be matched to the liver patients by age, sex, and weight to make fair comparisons.

All participants will take a single 20 mg dose of sevabertinib by mouth and stay in the research clinic for 5 days. During this time, researchers will take blood samples at specific times to measure how much drug is in the blood and how long it stays in the body. They will also monitor participants closely for any side effects.

The main goal is to see if people with liver problems have different drug levels in their blood compared to healthy people. This information will help doctors determine if cancer patients with liver disease need different doses of sevabertinib to be safe and effective.

The study will also look at the safety and tolerability of sevabertinib in both groups. Participants will have follow-up visits to ensure their continued health and safety.

This research is important because many cancer patients also have liver problems, and understanding how liver disease affects this new cancer treatment will help ensure it can be used safely and effectively in all patients who might benefit from it.

Conditions

Hepatic Insufficiency; Liver Diseases; Pharmacokinetics; Drug Metabolism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Arm A: Moderate Hepatic Impairment

Approximately 10 participants with moderate impaired hepatic function (Child-Pugh B) to achieve approximately 8 evaluable participants

Group Type: EXPERIMENTAL

Sevabertinib

Intervention Type: DRUG

Single oral dose of 20 mg sevabertinib administered as 2 x 10 mg film-coated tablets

Arm B: Normal Hepatic Function

Approximately 10 matched control participants for Arm A with normal hepatic function

Group Type: EXPERIMENTAL

Sevabertinib

Intervention Type: DRUG

Single oral dose of 20 mg sevabertinib administered as 2 x 10 mg film-coated tablets

Interventions

Sevabertinib

Single oral dose of 20 mg sevabertinib administered as 2 x 10 mg film-coated tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 18 to 79 years of age inclusive, at the time of signing the informed consent.
• Normal hepatic function or moderate hepatic impairment.
• Body weight of at least 50 kg and BMI of within the range 18 to 40 kg/m2 inclusive.
• Female, of non childbearing potential only. Females must not be pregnant or breastfeeding, and must be documented as of non-childbearing potential (WONCBP). A negative pregnancy test is required.
• Male study participants of reproductive potential must agree to use adequate contraception when sexually active from signing the Informed Consent Form (ICF) until at least 3 months after the last dose of study intervention, and refrain from sperm donation during study intervention and for 3 months after the last dose of study intervention.
• Signed ICF.

• Documented liver disease with findings consistent with cirrhosis confirmed by histopathology, laparoscopy, fibroscan, CT, MRI, or ultrasound, AND
• Hepatic impairment (Child-Pugh B), AND
• Stable liver disease (i.e., same Child-Pugh class for at least 2 months prior to screening).

• Have normal hepatic function, AND
• Fulfil Arm A matching criteria (sex, age, and body weight).

Exclusion Criteria

• Any existing relevant uncontrolled diseases of vital organs (e.g., heart, GI, pulmonary, or renal diseases), central nervous system (e.g., seizures), or other organs (e.g., uncontrolled diabetes mellitus [other than those related to hepatic impairment for the hepatically-impaired participants]) within 4 weeks prior to study intervention administration, including medically relevant infections and acute GI conditions (vomiting, diarrhea, and/or constipation).
• Known clinically relevant GI tract disorders (e.g., stomach ulcers, duodenal ulcers, GI bleeding, acute gastritis) or inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• Malignancy diagnosed or treated within the past 5 years (hepatocellular carcinoma within the past 2 years). Note: This does not include adequately-treated basal cell carcinoma or localized squamous cell carcinoma of the skin.
• Participants with primary or secondary biliary cirrhosis, or with sclerosing cholangitis.
• Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination, and effects of the study intervention will be affected.
• Renal impairment with an eGFR ≤40 mL/min according to the CKD-EPI equation.
• Use of strong or moderate CYP3A4 inducers or inhibitors within 4 weeks or 5 half-lives prior to study intervention administration (whichever is longer) until last day of blood sampling for PK after study intervention administration.
• Use of drugs which may affect absorption, unless the drug is part of the mandatory dosing regimen for treatment of hepatic impairment or related conditions.
• Use of supplements or herbal remedies within 2 weeks prior to the first study intervention administration (except for vitamin supplementation).
• Use of anti-coagulant drugs.
• Positive alcohol blood/urine test at screening.
• Positive blood/urine drug screening indicating drug abuse (except for participants with hepatic insufficiency on an approved prescription for opioids or benzodiazepines who agree to withhold the use of opioids or benzodiazepines from 12 hours pre- and 12 hours post-intervention administration).
• Insufficiently controlled diabetes mellitus with HbA1c >10% within 6 months prior to study intervention administration.
• Consumption of food and beverages containing grapefruit, Seville orange, tangelo, or pomelos within 2 weeks prior to study intervention administration and up to the last PK sampling.
• Special diets preventing the participants from eating the standard meals during the study or unwillingness to eat the standard meals during the study.
• Use of recreational drugs, carnitine products, anabolics, or high dose vitamins (except for medication against vitamin deficiency in hepatic impairment).
• Smoking more than 10 cigarettes daily (including vaping equivalent to approximately 10 cigarettes daily), or, unwilling to refrain from smoking and/or vaping from 22:00 on the day prior to study intervention administration and on Day 1 until 12 hours after study intervention administration.

• Ascites qualitatively estimated as severe or requiring acute or frequent paracentesis (no emptying and/or albumin supplementation required within 30 days prior to Day 1 [or at least within 14 days], or during the course of the study, as judged by the investigator), or a recent history of paracentesis.
• Encephalopathy of Grade >2. Examinations
• ALP ≥4 × ULN.
• AST or ALT in conjunction with GGT ≥4 × ULN (an isolated elevation of GGT ≥4 × ULN will not exclude the participant).
• Platelet count <60 × 10^9/L.
• Hemoglobin <9 g/dL.
• Serum albumin <2 g/dL.
• INR >2.3.

• Increase of liver enzymes (e.g., ALT, AST, GGT, or total bilirubin) above ULN.
• Increase of lipase and amylase (except isolated marginal increases of lipase or amylase to account for variability of the parameters, and the participant is asymptomatic and has no other laboratory changes assuming disease based on medical judgment).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Pharmacology of Miami, LLC - Oncology Department

Miami, Florida, United States

Site Status: RECRUITING

Orlando Clinical Research Center

Orlando, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Bayer Clinical Trials Contact

Role: CONTACT

clinical-trials-contact@bayer.com

(+)1-888-84 22937

Other Identifiers

22988

Identifier Type: -

Identifier Source: org_study_id