The purpose of this study is to evaluate the effect of JNJ-63623872 on the QT/QTc interval at supratherapeutic exposure in healthy participants (Panel 2).
This is a two-part Phase 1 study consisting of a dose escalation part (Panel 1) and a thorough QT (TQT) part (Panel 2). Panel 1 will be a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study medication assigned to participants by chance), placebo-controlled dose escalation study in healthy participants to determine the safety, tolerability and pharmacokinetics of JNJ-63623872 after administration of single doses of 2400 milligrams (mg) and 3000 mg under fasted conditions. The final dose to be used in the Panel 2 will be determined based on the results of this dose escalation part. An interim analysis will be conducted on Panel 1 to select the dose for Panel 2. Panel 2 will be a double-blind, double-dummy, randomized, 3-period crossover (the same medications provided to all participants but in different sequence), placebo- and positive controlled study to evaluate the effect of JNJ-63623872 on the QT/QTc interval in healthy participants. Participants' safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
66
Participants will receive JNJ-63623872 2400 mg tablet orally once on Day 1 of Panel 1.
Participants will receive JNJ-63623872 3000 mg tablet orally once on Day 1 of Panel 1.
Participants will receive JNJ-63623872 dose selected in Panel 1 tablet orally once on Day 1 of Panel 2.
Unnamed facility
Antwerp, Belgium
Change From Baseline in Corrected QT Interval (QTc) at Different Time Points
Electrocardiogram will be collected by Holter monitoring. The measured QT data will be corrected for heart rate using Fridericia (QTcF), Bazett (QTcB), and study-specific power (QTcP) correction methods. The QTcF as primary correction method.
Time frame: 45, 30 and 15 minutes predose and 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose on Day 1
Maximum Observed Concentration (Cmax)
The Cmax is the maximum observed concentration.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, Treatment C of Dose Level 2 (Panel 1) and Treatment E (Panel 2)
Time To Reach The Maximum Observed Concentration (Tmax)
The Tmax is the actual sampling time to reach the maximum observed concentration.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, Treatment C of Dose Level 2 (Panel 1) and Treatment E (Panel 2)
Observed Concentration at 24 Hours Post Dosing (C24h)
The C24h is the observed concentration at 24 hours post dosing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
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Participants will receive moxifloxacin 400 mg capsule orally once on Day 1 of Panel 2.
Participants will receive placebo (matching with JNJ-63623872 2400 mg) tablet orally once on Day 1 of Panel 1.
Participants will receive placebo (matching with JNJ-63623872 3000 mg) tablet orally once on Day 1 of Panel 1 and 2.
Participants will receive placebo (matching with JNJ-63623872 dose) tablet orally once on Day 1 of Panel 2.
Participants will receive placebo (matching with Moxifloxacin) tablet orally once on Day 1 of Panel 2.
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinite Time (AUC[0-infinity])
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
Area Under the Concentration Versus Time Curve (AUC) From Time of Administration up to 24 Hours Post Dosing (AUC24h)
The AUC24h is the area under the concentration versus time curve (AUC) from time of administration up to 24 hours post dosing.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1 of Treatment E (Panel 2)
Elimination Rate Constant (Lambda[z])
Lambda (z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
Apparent Terminal Elimination Half-life (t1/2term)
The T1/2term is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
Number of Participants with Adverse Events (AEs) and Serious AEs
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Screening up to Follow-up (10 to 14 days after last study drug administration)