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.

Inclusion Criteria:Is 18 to 50 years of age inclusive, at the time of signing the informed consentAre 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 drugsPresence 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 interventionPresence 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 PointesCurrent 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 disordersHistory (within past 2 years at Screening) or presence of substance use disorder (including alcohol) or seeking treatment for alcohol or substance abuse related disorderHistory of seizure disorder or a physical condition that would increase seizure riskHistory of head trauma or concussions that are deemed clinically significant by the investigatorHave 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 studyParticipants 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 studyPositive alcohol test or urine drug screen (including cannabinoids and cotinine) at Screening or at any point throughout the duration of the studyPresence at Screening of HIV antibody, Hepatitis B surface antigen, Hepatitis C antibody, or a clinical history of these infectionsHistory of clinically significant acute or chronic insomnia within the last 5 years