A Study to Assess the Effects of Itraconazole and Rifampin on Lazertinib in Healthy Adult Participants

A Phase 1 Open-Label, Fixed-Sequence Drug-Drug Interaction Study to Evaluate the Effects of Steady-state Itraconazole and Rifampin on the Single-dose Pharmacokinetics of Lazertinib Tablets in Healthy Adult Participants

The purpose of this study is to evaluate the effects of multiple doses of strong cytochrome P450 (CYP) 3A4 inhibitor itraconazole and strong CYP3A4 inducer rifampin on the single dose pharmacokinetics (PK) of lazertinib in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lazertinib; Drug: Itraconazole; Drug: Rifampin

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A woman must not be of childbearing potential and must have a negative serum beta-human chorionic gonadotropin (Beta HCG) pregnancy test at screening
• Hormone replacement therapy (if applicable) must have been discontinued at least 28 days prior to the first dose of study drug (Cohort 2 only)
• Participants must have a body mass index (BMI) between 18.0 and 32.0 kilogram per meter square (kg/m^2, inclusive (BMI = weight/height^2), and body weight not less than 50 kg at screening
• Participants must be healthy based on physical examination, medical history, and vital signs (pulse and body temperature), performed at screening
• Male participants must agree to use an adequate contraception method

Exclusion Criteria:

• History of or current clinically significant medical illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• 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 its excipients or to itraconazole and rifampin
• Participant has contraindications to the use itraconazole and rifampin per local prescribing information
• Use of any cytochrome P450 (CYP) 3A4 inhibitors or inducers (other than per-protocol itraconazole/rifampin administration) within 4 weeks before the first dose of the study drug is scheduled until completion of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Lazertinib plus Itraconazole; Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by itraconazole capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.	Drug: Lazertinib; Lazertinib tablets will be administered orally.; Other Names: JNJ-73841937; YH25448; Drug: Itraconazole; Itraconazole capsules will be administered orally.
Experimental: Cohort 2: Lazertinib plus Rifampin; Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by rifampin capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.	Drug: Lazertinib; Lazertinib tablets will be administered orally.; Other Names: JNJ-73841937; YH25448; Drug: Rifampin; Rifampin capsules will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 and 2: Maximum Plasma Concentration (Cmax) of Lazertinib	Cmax is defined as maximum plasma concentration.	Predose up to 120 hours post dose
Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time 0 to 120 Hours (AUC [0-120h]) of Lazertinib	AUC (0-120h) is defined as area under the plasma concentration-time curve from time 0 to 120 hours postdose.	Predose up to 120 hours post dose
Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Timepoint (AUC [0-last]) of Lazertinib	AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to time of last quantifiable timepoint.	Predose up to 120 hours post dose
Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-inf]) of Lazertinib	AUC (0-inf) 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 measurable (non-below limit of quantification) concentration.	Predose up to 120 hours post dose
Cohort 1 and 2: Percentage of Area Under the Plasma Concentration from time Zero to Infinite time obtained by Extrapolation (%AUC [0-inf],ex) of Lazertinib	%AUC (0-inf),ex is defined as percentage of area under the plasma concentration from time zero to infinite time obtained by extrapolation, calculated as (AUC [0-infinity] minus AUC [0-last]/AUC [0-infinity])*100.	Predose up to 120 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 and Cohort 2: 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 65 days (Cohort 1) and up to 70 days (Cohort 2)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): December 30, 2020
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 1, 2021
• Last Update Submitted That Met QC Criteria: February 25, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Protein Kinase Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole; Lazertinib
• Other Study ID Numbers: CR108799; 73841937NSC1003 (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