This study will characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) of JZP269 in healthy participants.
This first-in-human study is designed to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) of JZP269, an orexin-2 receptor agonist, in healthy participants. The study will also assess the effect of food on JZP269 PK, characterize cerebrospinal fluid (CSF) exposure, and evaluate the wake-promoting PD effects using the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS) in sleep-deprived participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
188
Number of Participants Reporting Treatment-emergent Adverse Events
Time frame: Day 1 of dosing and monitoring period up to 7 days after last dose (Safety Follow Up Visit)
Pharmacokinetic Parameter Maximum Concentration (Cmax) of JZP269
Time frame: Predose up to 48 hours postdose
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of JZP269
Time frame: Predose up to 48 hours postdose
Pharmacokinetic Parameter Apparent Terminal Elimination Half-life (t1/2) of JZP269
Time frame: Predose up to 48 hours postdose
Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP269
Area under the concentration-time curve from time 0 to 24 hours (AUC0-24), area under the concentration time curve from time 0 to the last measurable concentration (AUC0-last), and area under the concentration-time curve from time 0 to infinity will be assessed (AUC∞).
Time frame: Predose up to 48 hours postdose
Pharmacokinetic Parameter Oral Clearance (CL/F) of JZP269
Time frame: Predose up to 48 hours postdose
Pharmacokinetic Parameter Apparent Volume of Distribution During the Terminal Phase (Vz/F) of JZP269
Time frame: Predose up to 48 hours postdose
Dose Proportionality of JZP269 Area Under the Concentration-Time Curve (AUC)
Dose proportionality of JZP269 AUC0-last, AUC∞, and AUC0-24 will be assessed.
Time frame: Predose up to 48 hours postdose
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Dose Proportionality of JZP269 Maximum Concentration (Cmax)
Time frame: Predose up to 48 hours postdose
The Effect of Food on the PK of JZP269 Cmax
The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed.
Time frame: Predose up to 48 hours postdose
The Effect of Food on the PK of JZP269 Tmax
The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed.
Time frame: Predose up to 48 hours postdose
The Effect of Food on the PK of JZP269 t1/2
The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed.
Time frame: Predose up to 48 hours postdose
The Effect of Food on the PK of JZP269 AUC
The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed.
Time frame: Predose up to 48 hours postdose
Mean Concentrations of JZP269 in Cerebrospinal Fluid
Time frame: Predose up to 48 hours postdose
Mean Sleep Latency on the Maintenance of Wakefulness Test (MWT) in Sleep-deprived Participants
The MWT measures a participant's ability to remain awake under quiet conditions during the day. Sleep latency is the time it takes for a participant to fall asleep while trying to remain awake during the MWT, and sleep onset is determined objectively by electroencephalography. The MWT calculates mean sleep latency as the average time to sleep onset. Shorter mean sleep latency indicates a greater difficulty maintaining wakefulness.
Time frame: Day 1 of dosing and monitoring period
Mean Karolinska Sleepiness Scale (KSS) Score in Sleep-deprived Participants
The KSS is a 9-point scale that measures subjective sleepiness during the preceding 10 minutes, ranging from 1 ("extremely alert") to 9 ("very sleepy, great effort to keep awake, fighting sleep"). Higher scores indicate greater sleepiness.
Time frame: Day 1 of dosing and monitoring period