The purpose of this study is to assess the safety and tolerability of JNJ-63733657 following single ascending intravenous (IV) dose administration in healthy Japanese participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
Single ascending IV low, middle, and high dose of JNJ-63733657 will be administered in sequential cohorts. The progression to the next (higher) dose level is dependent on acceptable safety and tolerability profile of JNJ-63733657 obtained after dose administration of the current dose level. The length of time between dosing days of cohorts will be at least 14 days.
Participants will receive matching placebo intravenously.
Souseikai Fukuoka Mirai Hospital
Fukuoka, Japan
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Approximately 23 weeks
Maximum Observed Serum Concentration (Cmax) of JNJ-63733657
The Cmax is the maximum observed serum concentration.
Time frame: Up to Day 106
Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-63733657
The Tmax is defined as actual sampling time to reach maximum observed serum concentration.
Time frame: Up to Day 106
Area Under the Serum Concentration-Time Curve from Time Zero to Time to 56 Days (AUC [0-56days])
The AUC (0-56days) is the area under the serum concentration versus time curve from time 0 to time to 56 days after the start of infusion.
Time frame: 0 hours (Day 1) up to 56 days
Area Under the Serum Concentration-Time Curve from Time Zero to the Time Corresponding to Last Quantifiable Serum Concentration (AUC [0-last])
The AUC (0-last) is the area under the serum concentration-time curve from time zero time to the time corresponding to the last quantifiable serum concentration.
Time frame: Up to Day 106
Area Under the Serum Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity])
The AUC (0-infinity) is the area under the serum concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z); wherein AUC(0-last) is area under the serum concentration-time curve from time zero to last quantifiable time, C(last) is the last observed measurable serum concentration, and lambda(z) is elimination rate constant.
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Time frame: Up to Day 106
Elimination Rate Constant (Lambda[z]) of JNJ-63733657 in Serum
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 106
Apparent Elimination Half-Life (t1/2) of JNJ-63733657 in Serum
The elimination half-life (t1/2) is the time measured for the serum 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 106
Total Systemic Clearance (CL) of JNJ-63733657 in Serum
Systemic clearance is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the serum area under the plasma concentration-time curve from time zero to infinite time (AUC\[0-infinity\]).
Time frame: Up to Day 106
Volume of Distribution (Vz) of JNJ-63733657 in Serum
The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Up to Day 106
JNJ-63733657 Concentration in Cerebrospinal Fluid (CSF)
CSF concentration assessments will be done for JNJ-63733657.
Time frame: Up to Day 92
Number of Participants with Anti-JNJ-63733657 Antibodies
Number of participants with anti-JNJ-63733657 antibodies will be determined in serum samples.
Time frame: Up to Day 106
Percentage Change from Baseline in Total, Free, and Bound tau Biomarker Fragments in CSF
Percentage change from baseline in total, free, and bound tau (phosphorylation site) biomarker fragments in CSF will be evaluated to assess the effect of JNJ-63733657.
Time frame: Up to Day 92