Testing how zongertinib is absorbed in people with and without liver problems

Pharmacokinetics, Safety and Tolerability of Zongertinib Following Oral Administration in Male and Female Participants of Non-childbearing Potential With Different Degrees of Hepatic Impairment (Child-Pugh Classification A and B) Compared With Matched Male and Female Participants of Non-childbearing Potential With Normal Hepatic Function (an Open-label, Non-randomised, Single-dose, Parallel, Individual-matched Design Trial)

This study is testing how well the medication zongertinib is absorbed in adults with liver problems compared to those without any liver issues.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Boehringer Ingelheim (Industry-sponsored)
• Drugs / interventions: zongertinib
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT06692322 on ClinicalTrials.gov

What this trial studies

This study involves adults aged 18 to 80 with varying degrees of liver problems and healthy individuals as controls. Participants will take zongertinib tablets once, and those with liver issues will be monitored closely in a step-by-step approach to ensure they can tolerate the treatment. The study lasts about 5 weeks, requiring four visits to the study site, including an overnight stay. The goal is to understand how liver conditions affect the absorption and handling of zongertinib in the body.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 80 with mild to moderate liver problems or healthy individuals for comparison.

Not a fit: Patients with severe liver problems or those who are pregnant or breastfeeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment strategies for patients with liver problems by providing insights into how their condition affects medication absorption.

How similar studies have performed: Other studies have explored similar pharmacokinetic assessments in patients with liver conditions, indicating potential for success in this approach.

Eligibility criteria

inclusion criteria

* Male or female subjects of non-childbearing potential. Female subjects must be of non-childbearing potential either be a) postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of Follicle stimulating hormone (FSH) above 25 U/L and estradiol below 30 ng/L is confirmatory) or b) have proof of acceptable surgical sterilization. Subjects must use condom from time point of administration of trial medication until 30 days after drug administration.
* Age of 18 to 80 years (inclusive)
* Body mass index (BMI) of 18.0 to 42 kg/m\^2 (inclusive)
* Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
* Male subjects with Women of child-bearing potential (WOCBP) partner must be willing to use highly effective methods of contraception (condom in combination with other methods or sexual abstinence) from time point of administration of trial medication until 30 days thereafter. These include:

  * Subject uses condoms
  * Subject is sexually abstinent
  * Subject is vasectomized (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) and uses condom

Additionally female partners of male subjects must be willing to use any of the following criteria for a highly effective contraception from at least 30 days before the first administration of the male partner until 30 days thereafter:

* Use of intrauterine device or intrauterine hormone-releasing system by female partner plus use of condom
* Use of progestogen-only hormonal contraception by female partner that inhibits ovulation (injectables or implants) plus use of condom
* Use of combined (estrogen and progestogen containing) hormonal contraception by female partner that prevents ovulation (oral, intravaginal, or transdermal) plus use of condom
* Surgically sterilised (including hysterectomy or bilateral tubular occlusion) plus use of condom
* Postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of FSH above 25 U/L and estradiol below 30 ng/L is confirmatory) plus use of condom

  * For group 1 and 2 only: Hepatic impairment classified as Child-Pugh A (score 5-6 points) or Child-Pugh B (score 7-9 points)
  * For group 1 and 2 only: Absence of clinically significant abnormalities, as based on a complete medical history including a full physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12- lead Electrocardiogram (ECG), and clinical laboratory tests at both screening and admission to trial site, with the exception of findings that in the opinion of the investigator are consistent with the participant's hepatic impairment
  * For group 1 and 2 only: Medication and/or treatment regimens must have been stable (i.e., no dose adjustments) for at least 4 weeks prior to the screening period and should be kept stable until study completion Fluctuating treatment regimens may be considered for inclusion on a case-by-case basis if the underlying disease is under control in the opinion of the investigator and must be agreed to by both the investigator and the sponsor's medical monitor Further inclusion criteria apply.

exclusion criteria

* Any finding in the medical examination (including BP, PR or ECG) assessed as clinically relevant by the investigator (apart from any non-severe hepatic impairment and associated underlying diseases)
* Severe hepatic impairment (classified as Child-Pugh C or score 10-15)
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance (apart from values due to underlying disease)
* Any evidence of a concomitant disease assessed as clinically relevant by the investigator (apart from underlying disease)
* Severe gastrointestinal, renal (Estimated glomerular filtration rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) \<40 ml/min/1.73 m2 for the hepatic impaired patients and eGFR CKD-EPI \<90 ml/min/1.73 m2 for matched controls), respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the Investigator.
* Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
* History of relevant orthostatic hypotension, repetitive fainting spells, or repetitive blackouts Further exclusion criteria apply.

Where this trial is running

San Antonio, Texas

• American Research Corporation at the Texas Liver Institute — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Boehringer Ingelheim

Conditions Liver Diseases; Healthy