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

NCT05720494 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: JZP441-102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Healthy Participants; JZP441

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Treatment-emergent Adverse Events

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

• Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP441

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

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

  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.

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

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

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

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

  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.

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

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

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

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

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

• Pharmacokinetic Parameter Accumulation Ratio of JZP441

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

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

• Dose Proportionality of JZP441 for Maximum Concentration (Cmax)

  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.

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

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

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

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

Study Arms (2)

JZP441

EXPERIMENTAL

Healthy participants who will be randomized to receive an oral dose of JZP441.

Drug: JZP441

Placebo

PLACEBO COMPARATOR

Healthy participants who will be randomized to receive placebo.

Drug: Placebo

Interventions

JZP441 DRUG

Oral study drug administered for up to 4 weeks

JZP441

Placebo DRUG

Oral placebo administered for up to 4 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

Clinical Site 1

Salt Lake City, Utah, 84124, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: February 9, 2023
• Study Start: January 26, 2023
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: October 1, 2024

Record last verified: 2024-09

Locations

US (1)