A Study to Investigate The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JZP441 in Sleep-deprived Healthy Participants

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Nighttime Doses of JZP441 in Sleep-Deprived Healthy Participants: A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study

This Phase 1, double-blind, randomized, placebo-controlled study will characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ascending nighttime doses of JZP441 in sleep-deprived healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: JZP441; Drug: Placebo

Detailed Description

This study will initially employ nighttime dosing in sleep-deprived healthy participants. Participants (up to 12 per cohort) will be randomized to study intervention. Participants will remain awake during the day and then will be dosed at night. Safety, tolerability, PK and PD assessments will be conducted for nighttime dose.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Clinical Site 1
  • New York
    • New York, New York, United States, 10016
      • Clinical Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 to 50 years of age inclusive, at the time of signing the informed consent
• Are overtly healthy as determined by medical evaluation, including medical history, physical exam, laboratory tests, and cardiac/blood pressure monitoring

Exclusion Criteria:

• Female participants who are pregnant, nursing, or lactating
• History or presence of clinically significant allergy or allergy to band aids, adhesive dressing, electrocardiogram (ECG) patches, or medical tape
• History or presence of gastrointestinal (including prior bariatric bypass surgery), hepatic or renal disease, or any other condition that may interfere with absorption, distribution, metabolism, or excretion of drugs
• Presence of renal impairment or calculated creatinine clearance < 80 mL/min
• Triplicate 12-lead ECG demonstrating a mean QTcF > 450 msec for males and > 470 msec for females or any other clinically significant ECG abnormality per investigator assessment at Screening or Day -1
• Presence or history of significant cardiovascular disease including but not limited to: myocardial infarction, uncontrolled hypertension, systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg (at Screening or Day -1), angina pectoris, clinically significant arrhythmias, clinically significant valvular heart disease, history of any revascularization procedures or second or third-degree heart block with/without a pacemaker, heart failure, or family history of Torsades de Pointes
• Laboratory value(s) outside the laboratory reference range that are considered to be clinically significant by the investigator
• Current diagnosis of or receiving treatment for depression; past (within 5 years) major depressive episode according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria; history of suicide attempt, current suicidal risk as determined from history, or presence of active suicidal ideation
• History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria
• Participation in another clinical study of an investigational drug or medical device within 30 days or 5 half-lives (whichever is longer) prior to check-in on Day -1
• Presence at Screening of human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or a clinical history of these infections
• History of chronic insomnia (as defined by DSM-5 criteria)
• Has been diagnosed with sleep apnea or been identified as being at high risk for sleep apnea by standardized questionnaire (STOP-BANG)
• Any clinically relevant medical, behavioral, or psychiatric disorder that is associated with excessive sleepiness

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: JZP441; Participants who will be randomized to receive an oral dose of JZP441.	Drug: JZP441; Nighttime oral dose
Placebo Comparator: Placebo; Participants who will be randomized to receive an oral dose of placebo.	Drug: Placebo; Nighttime oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-emergent Adverse Events After Administration of JZP441 in Sleep-deprived Healthy Participants	1 hour postdose up to Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP441	Pre-dose and multiple post-dose timepoints, up to 36 hours
Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of JZP441	Pre-dose and multiple post-dose timepoints, up to 36 hours
Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP441	Pre-dose and multiple post-dose timepoints, up to 36 hours

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Actual): November 15, 2023
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Participants; JZP441
• Other Study ID Numbers: JZP441-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No