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

A Phase 1, Open-label, Study in Healthy Participants to Evaluate the Effect of Steady State Concentrations of Lazertinib (JNJ-73841937) on the Single-dose Pharmacokinetics of Probe Substrates (Midazolam, Rosuvastatin, and Metformin)

The purpose of this study is to evaluate the effect of steady-state concentrations of lazertinib on the single-dose pharmacokinetics (PK) of probe substrates (midazolam, rosuvastatin, and metformin) in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lazertinib; Drug: Midazolam; Drug: Rosuvastatin; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy on the basis of medical history at screening only, and physical examination, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and at admission to the study center
• Healthy on the basis of clinical laboratory tests performed at screening and at admission to the study center.
• A woman who is considered surgically sterile but not postmenopausal, must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test on Study Day 1. (exemptions: pregnancy test not required in female participants with prior hysterectomy or prior bilateral oophorectomy)
• Male participants must agree to use an adequate contraception method as deemed appropriate by the investigator
• Non-smoker or not using tobacco containing products for at least 6 months before first study drug administration and test negative for cotinine at screening and Study Day 1

Exclusion Criteria:

• History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, that in the opinion of the investigator, with written concurrence with the sponsor's medical monitor is considered cured with minimal risk of recurrence)
• History of suspected or confirmed coronavirus disease 2019 within 4 weeks before intake of study drug, or tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at admission to the study site
• Known allergies, hypersensitivity, or intolerance to lazertinib or its excipients or probe substrates
• Taken any disallowed therapies, concomitant therapy before the planned first dose of study drug
• Had major surgery, (example, requiring general anesthesia) within 8 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 4 weeks after the last dose of study drug administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lazertinib + Probe Substrates of Midazolam, Rosuvastatin, and Metformin; Participants will receive a single oral dose of probe substrates of midazolam, rosuvastatin, and metformin on Day 1 under fasted conditions followed by a single oral dose of lazertinib under fed conditions from Day 5 to Day 14 except Day 13 which is under fasted conditions and co-administered with probe substrates under fasted conditions on Day 13.

Drug: Lazertinib; Lazertinib tablets will be administered orally, alone or in combination with probe substrates.; Other Names: JNJ-73841937; YH25448; Drug: Midazolam; Midazolam (cytochrome P450 3A4 [CYP3A4] substrate) will be administered orally as a syrup as a part of probe substrates.; Drug: Rosuvastatin; Rosuvastatin (breast cancer resistant protein [BCRP] substrate) tablet will be administered orally as a part of probe substrates.; Drug: Metformin; Metformin (organic cation transporter 1 [OCT1] substrate) will be administered orally as a syrup as a part of probe substrates.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Probe Substrates (Midazolam, Rosuvastatin, and Metformin) Co-administered with Lazertinib (Day 13) as Test Versus Plasma Concentration of Probe Substrates Administered Alone (Day 1) as Reference	Plasma samples will be analyzed to determine concentrations of midazolam and its metabolite 1-OH-midazolam, rosuvastatin, metformin, or lazertinib using a validated, specific, and sensitive method on Day 1 versus Day 13 as a part of drug-drug interaction (DDI) assessment.	Predose up to 12 hours postdose (Days 1 and 13)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Clinically Significant Abnormalities in 12-lead Electrocardiograms (ECGs)	Number of participants with clinically significant abnormalities in ECGs will be reported.	Up to 28 days
Number of Participants with Adverse Events (AEs)	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 56 days
Number of Participants with AEs by Severity	Number of participants with AEs by severity will be reported. AE severity is a clinical determination of the intensity of an AE and is assessed by using the standard grades as follows: Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to AE.	Up to 56 days
Number of Participants with Clinically Significant Changes in Laboratory Test Results	Number of participants with change in clinical laboratory test results (including hematology and serum chemistry) will be reported.	Up to 28 days
Number of Participants with Clinically Significant Abnormalities in Vital Signs	Number of participants with clinically significant abnormalities in vital signs (including temperature [oral], pulse rate, and blood pressure) will be reported.	Up to 28 days
Number of Participants with Clinically Significant Abnormalities in Physical Examination	Number of participants with clinically significant abnormalities in physical examination (including height and body weight) will be reported.	Up to 28 days
Plasma Concentrations of Lazertinib at steady-state	Plasma concentration of lazertinib at steady-state will be assessed.	Predose on Day 7, 9, 11, 13, and 14
Plasma Concentrations of Lazertinib Following Repeat Dosing for 10 Days	Plasma concentration of lazertinib following repeat dosing for 10 days will be assessed.	Day 14, 15, 16, 17, 21, and 28

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): February 10, 2022
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Protein Kinase Inhibitors; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Rosuvastatin Calcium; Metformin; Lazertinib
• Other Study ID Numbers: CR109080; 73841937NSC1008 (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: Yes
• Studies a U.S. FDA-regulated device product: No