The main purpose of this study is to determine the potential inhibitory/inducing effects of JNJ-54175446 after single and repeated dosing on the single-dose pharmacokinetics (PK) of a cocktail, containing selective probes of cytochrome P450 (CYP) enzymes (CYP3A4/A5, CYP2C9, CYP1A2, CYP2D6, CYP2B6, and CYP2C19) in healthy adult subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Subjects will receive JNJ-54175446 150 mg capsules orally (1\*100 mg + 1\*50 mg) under fasted conditions on Day 7, 9, 10 and 11.
Subjects will receive JNJ-54175446 600 mg (6\*100 mg capsules) orally on Day 8.
Subjects will receive midazolam 2 mg oral emulsion \[2 (milligram per milliliter (mg/mL)\] as a drug cocktail on Day 1, 7 and 11.
Subjects will receive warfarin 10 mg tablets (2\*5 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive caffeine 50 mg tablet (1\*50 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive dextromethorphan 30 mg capsule (1\*30 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive Bupropion 150 mg tablet (1\*150 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive omeprazole 20 mg capsule (1\*20 mg) orally as a drug cocktail on Day 1, 7 and 11.
Clinical Pharmacology Unit
Merksem, Belgium
Maximum Observed Plasma Concentration (Cmax)
The Cmax is the maximum observed plasma concentration.
Time frame: Up to Day 17
Plasma Trough Concentration (Ctrough)
Ctrough is defined as observed plasma concentration of drug just prior to the beginning or at the end of a dosing interval.
Time frame: Up to Day 17
Time to Reach Maximum Observed Plasma Concentration (Tmax)
The Tmax is defined as actual sampling time to reach maximum observed concentration.
Time frame: Up to Day 17
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last])
The AUClast is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit) concentration.
Time frame: Up to Day 17
Area Under the Plasma Concentration-Time Curve From Time Zero 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: Up to Day 17
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: Up to Day 17
Elimination Half-Life (t1/2)
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: Up to Day 17
Apparent Total Clearance (CL/F)
Apparent total clearance is calculated as dose/AUC(0-infinity).
Time frame: Up to Day 17
Apparent Volume of Distribution (Vd/F)
Apparent volume of distribution, calculated as dose/(lambda\[z\]\*AUC\[0-infinity\]).
Time frame: Up to Day 17
Parent to Metabolite Ratio (Cmax)
Parent to metabolite ratio Cmax is defined as the ratio of individual Cmax values between parent and metabolite.
Time frame: Up to Day 17
Parent to Metabolite Ratio (AUC [Last])
Parent to metabolite ratio (AUC \[Last\]) is defined as ratio of individual (AUC \[Last\]) values between parent and metabolite.
Time frame: Up to Day 17
Parent to Metabolite Ratio (AUC [infinity])
Parent to Metabolite Ratio (AUC \[infinity\]) is defined as the ratio of individual (AUC \[infinity\]) values between parent and metabolite.
Time frame: Up to Day 17
Number of Subjects With Adverse Events (AEs) as a Measure of Safety and Tolerability
Safety and Tolerability
Time frame: Up to follow up (14 to 21 days after last dose)
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