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 Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
20
Lazertinib tablets will be administered orally, alone or in combination with probe substrates.
Midazolam (cytochrome P450 3A4 \[CYP3A4\] substrate) will be administered orally as a syrup as a part of probe substrates.
Rosuvastatin (breast cancer resistant protein \[BCRP\] substrate) tablet will be administered orally as a part of probe substrates.
PRA Health Sciences
Salt Lake City, Utah, United States
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.
Time frame: Predose up to 12 hours postdose (Days 1 and 13)
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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 28 days
Number of Participants with Clinically Significant Abnormalities in 12-lead Electrocardiograms (ECGs)
Number of participants with clinically significant abnormalities in ECGs will be reported.
Time frame: Up to 28 days
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Metformin (organic cation transporter 1 \[OCT1\] substrate) will be administered orally as a syrup as a part of probe substrates.
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.
Time frame: 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.
Time frame: Up to 28 days
Plasma Concentrations of Lazertinib at steady-state
Plasma concentration of lazertinib at steady-state will be assessed.
Time frame: 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.
Time frame: Day 14, 15, 16, 17, 21, and 28