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Completed

NCT Number: NCT05720494

A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JZP441 in Healthy Participants

Treatments for narcolepsy and hypersomnolence disorders should have good oral bioavailability and brain penetration properties. JZP441 has demonstrated wake-promoting efficacy and anticataplectic activity in nonclinical studies and may represent a novel approach for these patients.

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Key information

Conditions

Healthy Participants

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Site 1

Salt Lake City, Utah, 84124, United States

About this study

This Phase 1, double-blind, randomized, placebo-controlled, parallel group study is designed to characterize the safety, tolerability, and PK of multiple ascending doses of JZP441 for up to 4 weeks in healthy adult participants.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Is 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

  • History or presence of gastrointestinal (including prior bariatric bypass surgery), hepatic or renal disease, or any other condition that, in the investigator opinion, may interfere with absorption, distribution, metabolism, or excretion of drugs
  • Presence of renal impairment or calculated eGFR < 80 mL/min/1.73 m^2.
  • 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 prior to dose of study intervention
  • Presence or history of significant cardiovascular disease including (but not limited to): myocardial infarction, uncontrolled hypertension, systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg (at Screening or baseline consistent with protocol specifications), 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
  • Current diagnosis of or receiving treatment for depression; past (within 5 years) clinically significant major depressive episode; history of suicide attempt, current suicidal risk as determined from history, or presence of active suicidal ideation as indicated by a positive response to item 4 or item 5 on the C-SSRS (within the past 6 months)
  • History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or clinically significant psychiatric disorders, including other psychotic disorders
  • History (within past 2 years at Screening) or presence of substance use disorder (including alcohol) or seeking treatment for alcohol or substance abuse related disorder
  • History of seizure disorder or a physical condition that would increase seizure risk
  • History of head trauma or concussions that are deemed clinically significant by the investigator
  • Have used tobacco products or products for smoking cessation within 90 days before screening, including nicotine-containing products, or history of significant use of tobacco (> 10 cigarettes or equivalent per day) within 1 year before Screening, or unwilling to refrain from nicotine-containing products for the duration of the study
  • Participants who are taking a concomitant medication or supplement that lowers seizure threshold (eg, kratom)
  • Participants who have recently (< 2 weeks) discontinued a drug or supplement for which discontinuation would lower seizure threshold (eg, benzodiazepine medication)
  • Participation in a previous JZP441 clinical study
  • Positive alcohol test or urine drug screen (including cannabinoids and cotinine) at Screening or at any point throughout the duration of the study
  • Presence at Screening of HIV antibody, Hepatitis B surface antigen, Hepatitis C antibody, or a clinical history of these infections
  • History of clinically significant acute or chronic insomnia within the last 5 years

Treatment and study plan

JZP441

Drug

Oral study drug administered for up to 4 weeks

Placebo

Drug

Oral placebo administered for up to 4 weeks

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events

    Time frame: Day 1 up until 38 days after last dose of study drug, up to approximately 2 months

  2. Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

  3. Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

    Time to maximum plasma concentration (Tmax), time of maximum observed plasma concentration post first dose but before second dose during the 24-hour dosing interval (Tmax1), and time of maximum observed plasma concentration post second dose during the 24-hour dosing interval (Tmax2), and time of last quantifiable concentration (Tlast) will be assessed.

  4. Pharmacokinetic Parameter Terminal Elimination Half-life (T1/2) of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

  5. Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

    Area under the concentration-time curve from time 0 to 24 hours (AUC0-24), area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC∞) will be assessed.

  6. Pharmacokinetic Parameter Apparent Oral Clearance (CL/F) of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

  7. Pharmacokinetic Parameter Apparent Volume of Distribution (Vz/F) of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

  8. Pharmacokinetic Parameter Accumulation Ratio of JZP441

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

    Accumulation ratio (Cmax) and accumulation ratio (AUC) will be assessed.

  9. Dose Proportionality of JZP441 for Maximum Concentration (Cmax)

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

    Dose proportionality of maximum concentration (Cmax), maximum observed plasma concentration post first dose but before second dose during the 24-hour dosing interval (Cmax1), and maximum observed plasma concentration post second dose during the 24-hour dosing interval (Cmax2) will be assessed.

  10. Dose Proportionality of JZP441 for Area Under the Concentration-Time Curve (AUC)

    Time frame: Pre-dose and multiple post-dose timepoints, up to Day 28

    Dose proportionality of area under the concentration-time curve from 0 to 24 hours (AUC[0-24]) will be assessed.

Sponsors and collaborators

Lead sponsor

Jazz Pharmaceuticals

Industry

Registry information

Official study title

Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of JZP441 in Healthy Adult Participants: A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Feb 9, 2023
Registry last updated
Oct 1, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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