Clareo Health | A Study Evaluating How Moderate Liver Impairment Affects the Absorption, Distribution, Metabolism, and Elimination of Sevabertinib After a Single Oral Dose
A Study Evaluating How Moderate Liver Impairment Affects the Absorption, Distribution, Metabolism, and Elimination of Sevabertinib After a Single Oral Dose
Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
Bayer
Age
18–79
Sex
ALL
Healthy volunteers
Accepted
You may be eligible if
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).
You may not be if
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, with the exception of cannabis (see below), carnitine products, anabolics, or high dose vitamins (except for medication against vitamin deficiency in hepatic impairment).
Cannabis containing products should be stopped 5 days prior to study intervention and should not be used during the in-house period of the study until after participant discharge from the clinic.
\- 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, ALT or GGT ≥4 × ULN.
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).
