A Study of (14C)-JNJ-73841937 (Lazertinib) in Healthy Male Participants

Healthy Clinical Trial

Official title:

An Open-Label Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-JNJ-73841937 (Lazertinib) After a Single Oral Dose in Healthy Male Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04410081
• Other study ID #: CR108791
• Secondary ID: 73841937NSC10042
• Status: Completed
• Phase: Phase 1
• Start date: July 14, 2020
• Est. completion date: March 2, 2021

Study information

• Verified date: March 2021
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize the absorption, metabolic pathways of lazertinib, and the excretion of the parent lazertinib and its metabolites, after a single oral dose of 14C-lazertinib in healthy adult male participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 2, 2021
• Est. primary completion date: March 2, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Must be healthy on the basis of medical history performed at screening and physical examination and vital signs (pulse rate and body temperature) performed at screening and admission to the study site

• Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry or hematology panel are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator

• Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2, inclusive (BMI = weight/height^2), and body weight not less than 50 kg at screening

• Blood pressure at screening and admission to the study site (after the participant supine for 5 minutes) between 90 and 140 millimeter of Mercury (mmHg) systolic, inclusive; and no higher than 90 mmHg diastolic at screening

• A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function, including: Sinus rhythm, Pulse rate between 45 and 100 beats per minute (bpm), corrected QT (QTc) interval less than or equal to (<=) 450 millisecond (msec), QRS interval of less than (<)120 msec, PR interval <210 msec

Exclusion Criteria:

• History of infection suspected or confirmed to be related to Coronavirus disease 2019 (COVID-19) within 4 weeks before intake of study drug

• Participant has known allergies, hypersensitivity, or intolerance to lazertinib or any of its excipients

• Participant has a positive test for hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg), hepatitis B (anti-HBc or anti-HBs), or hepatitis C (anti-HCV) antibodies positive at screening. Hepatitis B surface antibody positivity is not exclusionary if participant can provide evidence of Hepatitis B vaccination

• Participant who plans to father a child while enrolled in the study or within 6 months after study drug administration

• Exposure to radiation for professional or medical reasons with the exception of up to 2 standard diagnostic radiographs (example, [dental X-rays, plain chest X-ray]) within 1 year before study drug administration on Study Day 1. Participants cannot have participated in a radiolabeled drug study within 12 months prior to dosing if the dose was higher than 0.1 megabecquerel (MBq)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 14C-lazertinib
A single oral dose of 14C-lazertinib will be administered.

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of 14C-lazertinib	Cmax is defined as maximum observed plasma concentration.	Up to 99 days
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of 14C-lazertinib	Tmax is defined time to reach the maximum observed concentration.	Up to 99 days
Primary	Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUC [0-last]) of 14C-lazertinib	AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to the time of last observed quantifiable concentration.	Up to 99 days
Primary	Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of 14C-lazertinib	AUC (0-infinity) is defined as area under the plasma concentration-time curve from time 0 to infinity, calculated as the sum of AUC(0-last)+C(last)/ lambda(z), where C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Up to 99 days
Primary	Elimination Half-life (t1/2) of 14C-lazertinib	Elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve, calculated as 0.693/lambda(z).	Up to 99 days
Primary	Apparent Terminal Elimination Rate Constant (Lambda[z])	Lambda(z) is defined as apparent terminal elimination rate constant, estimated by linear regression using the terminal log-linear phase of the log transformed concentration vs time data.	Up to 99 days
Primary	Total Apparent Clearance (CL/F) of 14C-lazertinib	Clearance is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose/AUC (0-infinity).	Up to 99 days
Primary	Apparent Volume of Distribution (Vdz/F) of 14C-lazertinib	Apparent volume of distribution, calculated as dose/(Lambda(z)*AUC (0-infinity).	Up to 99 days
Primary	Ratio of Blood to Plasma Total Radioactivity of 14C-lazertinib	Blood to plasma total radioactivity ratio, calculated as blood total radioactivity/plasma total radioactivity.	Up to 99 days
Primary	Ratio of AUC (0-infinity) of 14C-lazertinib to AUC (0-infinity) of Total Radioactivity in Plasma	The ratio of AUC (0-infinity) of 14C-lazertinib to AUC (0-infinity) of total radioactivity in plasma will be assessed.	Up to 99 days
Primary	Ratio of AUC (0-last) of 14C-lazertinib Concentration to AUC (0-last) of Total Radioactivity in Plasma	The ratio of AUC (0-last) of 14C-lazertinib to AUC (0-last) of total radioactivity in plasma will be assessed.	Up to 99 days
Primary	Ratio of Cmax of 14C-lazertinib to Cmax of Total Radioactivity in Plasma	The ratio of Cmax of 14C-lazertinib to Cmax of total radioactivity in plasma will be assessed.	Up to 99 days
Primary	Ratio of 14C-lazertinib Concentration to Total Radioactivity in Plasma	The ratio of 14C-lazertinib concentration to total radioactivity in plasma for each sampling time point will be assessed.	Up to 99 days
Primary	Amount of 14C-lazertinib Excreted in Urine (Ae[t1-t2])	Amount excreted into the urine during a collection interval, where t1 and t2 are the start and end times of the collection interval, and calculated by multiplying the urinary volume with the urinary concentration for that interval.	Up to 99 days
Primary	Cumulative Amount of 14C-lazertinib Excreted in Urine (Ae)	Cumulative amount excreted into the urine over the entire collection period, calculated as the sum of Ae's across the collection intervals for each participant.	Up to 99 days
Primary	Percentage of 14C-lazertinib Dose Excreted in Urine (%Ae)	Cumulative amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae divided by dose)*100.	Up to 99 days
Primary	Renal Clearance (CLr) of 14C-lazertinib	The CLr is the renal clearance of the drug, calculated as Ae/AUC(0-infinity).	Up to 99 days
Primary	Amount of 14C-lazertinib Excreted in Feces (Fe[t1-t2])	Amount excreted into the feces during a collection interval, where t1 and t2 are the start and end times of the collection interval, and calculated by multiplying the feces weight with the feces concentration for that interval.	Up to 99 days
Primary	Cumulative Amount of 14C-lazertinib Excreted in Feces (Fe)	Cumulative amount excreted into the feces over the entire collection period, calculated as the sum of Fe's across the collection intervals for each participant.	Up to 99 days
Primary	Percentage of 14C-lazertinib Dose Excreted in Feces (%Fe)	Cumulative amount excreted into the feces, expressed as a percentage of the administered dose, calculated as (Fe divided by dose)*100.	Up to 99 days
Primary	Total Recovery of 14C-lazertinib Dose in Feces and Urine	Total recovery, calculated as sum of %Ae and %Fe.	Up to 99 days
Secondary	Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment.	Up to 135 days