A Study to Evaluate the Effect of Hepatic Impairment on Lazertinib (JNJ-73841937)

A Single-Dose, Open-Label, Parallel-Group, Multi-Center Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Lazertinib (JNJ-73841937)

The purpose of this study is to evaluate the pharmacokinetics (PK) of a single oral dose of lazertinib in participants with impaired hepatic function when compared with healthy participants with normal hepatic function, under fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: Lazertinib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • CRS Clinical Research Services Kiel GmbH
  • Munchen, Germany, 81241
    • Apex Gmbh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All Participants:

• Must have a clinically stable hepatic function as confirmed by the serum bilirubin and transaminase levels measured during screening and those measured on Day -1
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol
• If a woman, must not be of childbearing potential: postmenopausal (amenorrhea for at least 12 months and a serum follicle stimulating hormone within postmenopausal range); or surgically sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation procedure)

Healthy Participants with normal hepatic function:

• Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic for participants less than or equal to (<=) 60 years old and between 90 and 150 mmHg for participants greater than (>) 60 years old, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted per visit
• Pharmacogenomics: Healthy participants must have matching glutathione S-transferase Mu 1 (GSTM1) genotype (null or non-null GSTM1 genotype) to individual hepatic impairment group participants

Participants with hepatic impairment:

• A 12-lead electrocardiogram (ECG) consistent with adequate cardiac conduction and function as per judgement by the investigator, including: a) Sinus rhythm; b) Heart rate between 50 and 100 beats per minute (extremes included); c) QTc interval <= 480 milliseconds (ms) (corrected cf. Fridericia; QTcF)
• Concomitant medications to treat underlying disease states or medical conditions related to hepatic impairment are allowed. Participants must be on a stable dose of medication and/or treatment regimen for at least 2 weeks before dosing as well as during the study

Exclusion Criteria:

All Participants:

• Participant has known allergies, hypersensitivity, or intolerance to Lazertinib or its excipients
• Any surgical or medical condition that may alter the absorption, metabolism, or excretion of the study drug (example, gastrectomy, Crohn's disease etc.), with the exception of hepatic impairment
• Active gall bladder or biliary tract disease (example, acute cholecystitis, symptomatic cholelithiasis)
• Participant tests positive for human immunodeficiency virus (HIV)-1 or HIV-2 at screening
• Participant has a lack of adequate venous access

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Group 1: Moderate Hepatic Impairment; Participants with moderate hepatic impairment will receive a single oral dose of lazertinib.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: YH25448; JNJ-73841937,
Active Comparator: Part A: Group 2: Normal Hepatic Function; Participants with normal hepatic function who qualify for the control group will receive a single oral dose of lazertinib.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: YH25448; JNJ-73841937,
Experimental: Part B: Group 3 (Optional): Mild Hepatic Impairment; Participants with mild hepatic impairment will receive a single oral dose of lazertinib.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: YH25448; JNJ-73841937,
Experimental: Part B: Group 4 (Optional): Severe Hepatic Impairment; Participants with severe hepatic impairment will receive a single oral dose of lazertinib.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: YH25448; JNJ-73841937,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Lazertinib	Plasma concentrations of lazertinib will be analyzed using a validated, specific, and sensitive method to assess the effect of hepatic impairment on the pharmacokinetic of lazertinib.	Predose up to 312 hour postdose (up to Day 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 49 days

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): July 11, 2022

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Lazertinib
• Other Study ID Numbers: CR109022; 2021-001950-71 (EudraCT Number); 73841937NSC1007 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No