Healthy Participants
Conditions
Keywords
Healthy Participants, JZP269
Brief summary
This study will characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) of JZP269 in healthy participants.
Detailed description
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.
Interventions
Administered as described.
Administered as described.
Sponsors
Study design
Eligibility
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: 1. Is 18 to 55 years of age, inclusive, at the time of signing the informed consent. 2. Is overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac/blood pressure monitoring. 3. Has a body weight of at least 45 kg and BMI within the range of 18.5 to 30 kg/m\^2 (inclusive). Participants are excluded from the study if any of the following criteria apply: 1. Has a history of or presence of clinically significant medical illness as specified in the protocol. 2. Has a family history (first degree relative) of torsades de pointes, premature sudden death, long QT syndrome, or clinically significant cardiac conduction disorders. 3. Has a known or suspected history of schizophrenia or other psychotic illness or a history of severe personality disorder or other significant psychiatric disorder. 4. Has a history (within 5 past years) or presence of diagnosis of alcohol abuse or alcohol use disorder, substance abuse or substance use disorder, or known drug dependence or is seeking treatment for an alcohol or substance abuse related disorder. 5. Has a current diagnosis of or is receiving treatment for depression or has a history (within past 5 years) of clinically significant major depressive episode. 6. Has a history of suicide attempt, a current suicidal risk as determined from history, or the presence of active suicidal ideation as indicated by a positive response to Item 4 or Item 5 on the C-SSRS (within the past 24 months). 7. In participants where cerebrospinal fluid will be collected, any contraindications to lumbar puncture including increased intracranial pressure, conditions that may lead to brain herniation, a history of degenerative spine disease or lumbar spinal stenosis, a history of lumbar surgery, or prior history of adverse experience with lumbar puncture (eg, headache). 8. Has a clinically significant ECG abnormality per investigator assessment or an average PR \> 200 msec, average QRS \> 110 msec, average QTcF \> 440 msec for men and women, or flattened or difficult to distinguish T-waves. 9. Has a resting supine systolic blood pressure \> 140 mmHg or \< 90 mmHg, resting supine diastolic blood pressure \> 90 mmHg or \< 50 mmHg, or resting supine heart rate \> 100 bpm or \< 40 bpm at screening or check-in.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment-emergent Adverse Events | 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 | Predose up to 48 hours postdose | — |
| Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of JZP269 | Predose up to 48 hours postdose | — |
| Pharmacokinetic Parameter Apparent Terminal Elimination Half-life (t1/2) of JZP269 | Predose up to 48 hours postdose | — |
| Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP269 | Predose up to 48 hours postdose | 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∞). |
| Pharmacokinetic Parameter Oral Clearance (CL/F) of JZP269 | Predose up to 48 hours postdose | — |
| Pharmacokinetic Parameter Apparent Volume of Distribution During the Terminal Phase (Vz/F) of JZP269 | Predose up to 48 hours postdose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Proportionality of JZP269 Area Under the Concentration-Time Curve (AUC) | Predose up to 48 hours postdose | Dose proportionality of JZP269 AUC0-last, AUC∞, and AUC0-24 will be assessed. |
| Dose Proportionality of JZP269 Maximum Concentration (Cmax) | Predose up to 48 hours postdose | — |
| The Effect of Food on the PK of JZP269 Cmax | Predose up to 48 hours postdose | The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed. |
| The Effect of Food on the PK of JZP269 Tmax | Predose up to 48 hours postdose | The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed. |
| The Effect of Food on the PK of JZP269 t1/2 | Predose up to 48 hours postdose | The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed. |
| The Effect of Food on the PK of JZP269 AUC | Predose up to 48 hours postdose | The effect of food on the PK of JZP269 relative to that observed in the fasted state will be assessed. |
| Mean Concentrations of JZP269 in Cerebrospinal Fluid | Predose up to 48 hours postdose | — |
| Mean Sleep Latency on the Maintenance of Wakefulness Test (MWT) in Sleep-deprived Participants | Day 1 of dosing and monitoring period | 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. |
| Mean Karolinska Sleepiness Scale (KSS) Score in Sleep-deprived Participants | Day 1 of dosing and monitoring period | 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. |