A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JZP269 in Healthy Male and Female Participants

A Phase 1, Randomized, Double-Blind, Sponsor-Unblinded, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JZP269 in Healthy Male and Female Participants

This study will characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) of JZP269 in healthy participants.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: JZP269; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 188
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@JazzPharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JZP269; Participants will receive JZP269.	Drug: JZP269; Administered as described.
Placebo Comparator: Placebo; Participants will receive a matching placebo.	Drug: Placebo; Administered as described.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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∞).	Predose up to 48 hours postdose
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Proportionality of JZP269 Area Under the Concentration-Time Curve (AUC)	Dose proportionality of JZP269 AUC0-last, AUC∞, and AUC0-24 will be assessed.	Predose up to 48 hours postdose
Dose Proportionality of JZP269 Maximum Concentration (Cmax)		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.	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.	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.	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.	Predose up to 48 hours postdose
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	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.	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.	Day 1 of dosing and monitoring period

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Jazz Pharmaceuticals Ireland Limited

Study record dates

Study Major Dates

• Study Start (Estimated): September 22, 2026
• Primary Completion (Estimated): February 27, 2027
• Study Completion (Estimated): February 27, 2027

Study Registration Dates

• First Submitted: September 4, 2026
• First Submitted That Met QC Criteria: September 4, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Healthy Participants; JZP269
• Other Study ID Numbers: JZP269-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No