A Study to Investigate Efficacy, Safety, Tolerability, and Pharmacokinetics of JZP441 Compared With Placebo in Participants With Narcolepsy Type 1

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Is 18 to 64 years of age inclusive at the time of signing the informed consent.

2. Has a physician diagnosis of NT1 according to ICSD-3-TR criteria

3. Has an average sleep latency of less than 15 minutes, as documented by the mean of the first 4 trials of the Baseline MWT, as determined by central assessment.

4. Has a minimum body weight of 50 kg for men and 45 kg for women and a BMI within the range 18.0 to 35.0 kg/m^2 (inclusive).

5. Participant agrees to the following based on sex assigned at birth.

6. Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 90 days after the last dose of study intervention:

• Refrain from donating sperm

• Use contraception /barrier as specified in the protocol

2. Female participants are eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

• Is a woman of non-childbearing potential (WONCBP) OR

• Is a WOCBP and using a contraceptive method that is highly effective during the study intervention period and until completion of the Safety Follow-up Period.

• Male partners of WOCBP are required to use barrier protection, (eg, condoms) during the study intervention period and over the 90-day period after the last dose of study intervention.

• A WOCBP must have a negative highly sensitive pregnancy test at screening and at check-in on Day -1 of each Treatment Visit, before the first dose of study intervention is administered.

• If a urine test cannot be confirmed as negative, a serum pregnancy test is required.

6. Is capable of giving signed informed consent

Participants are excluded from the study if any of the following criteria apply:

1. Any other clinically relevant medical, behavioral, or psychiatric disorder other than NT1 that is associated with EDS.

2. History or presence of gastrointestinal (including gastric bypass surgery within the past 10 years), hepatic disease, untreated thyroid disease, or any other condition that may interfere with absorption, distribution, metabolism, or excretion of drugs.

3. Presence of severe renal impairment, end-stage renal disease or BSA-adjusted calculated eGFR <60 mL/min.

4. Presence of cardiodynamic abnormalities defined as triplicate 12-lead ECG

5. History or evidence of any of the following: myocardial infarction, cardiac surgery revascularization, unstable angina, cerebrovascular accident or stroke or TIA, pacemaker, atrial fibrillation, flutter, syncope in the past 2 years from a cardiac etiology or unexplained syncope or non-sustained or sustained VT. Angina pectoris greater than Class 1, CHF greater than NYHA Class 1, personal or family history of the Long QT Syndrome, Brugada syndrome, Wolff-Parkinson-White syndrome, any history of heart block, family history of sudden death.

6. Structural or functional heart abnormalities as determined by an echocardiogram performed within 6 months prior to screening, including LVEF <45%; moderate or greater aortic or mitral stenosis or regurgitation.

7. Presence or history of uncontrolled hypertension, systolic BP of at least 140 mmHg or diastolic BP of at least 90 mmHg (at Screening Visit, Baseline Visit, or prior to randomization).

8. Laboratory values (chemistry, hematology, and urinalysis) outside the laboratory reference range considered to be clinically significant by the investigator.

9. 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).

10. Current major depressive episode or presence of uncontrolled anxiety disorder according to DSM-5 criteria. Participants with stable treated depression and/or anxiety are allowed.

11. Current or history of psychotic or bipolar disorders, or any first degree relative with a history of schizophrenia-spectrum disorder or bipolar I disorder.

12. History (within the past year at screening) or presence of substance use disorder or alcohol use disorder per DSM-5 definition, known drug dependence, or seeking treatment for alcohol or substance use related disorder.

13. History of seizure disorder or a physical condition that would increase seizure risk.

14. History of ischemic event or a condition that elevates the participant's risk for an ischemic event

15. Evidence of untreated or inadequately treated sleep-disordered breathing

16. Concomitant or recent (within 5 half-lives) use of drugs that affect QT or QRS intervals, including sodium channel blockers.

17. Use of any medications that could affect the evaluation of EDS within a time period prior to the Baseline Visit corresponding to at least 5 half-lives of the drug(s) or planned use during the study.

18. Concomitant use of XYWAV, high sodium oxybate, or pitolisant. Other medications used for treatment of cataplexy (eg, antidepressants) are allowed.

19. Participation in another clinical study of an investigational drug (other than JZP441) or medical device within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention and throughout the duration of the study.

20. Habitual bedtime later than 1:00 AM over the last 6 months, per self-report.

21. Occupation requiring nighttime shift work or variable shift work.

22. Travel across 3 or more time zones within 1 week of Baseline Visit or planned through duration of treatment.