Clinical Trial of Solriamfetol for Excessive Sleepiness Related to Shift Work Disorder

Inclusion Criteria:

1. Men and women

2. Ages 18 to 64 years

3. Early-morning shift workers with a fixed work schedule (start times between 3 AM-6AM, for at least 3 days per week)

4. ≥ 20 work hours per week, 6-hour to 12-hour shifts

5. ≥ 3-month history of working early morning shifts prior to the study

6. Shift work disorder (as measured by 4-item SWD screening questionnaire and SWDsymptoms confirmed by clinician) with excessive sleepiness (as measured by themodified ESS) specifically related to early morning shifts

7. Baseline MWT average sleep latency <20 minutes on the first 4 scheduled naps

8. Body mass index 18.5 to 45 kg/m2

9. Normal thyroid stimulating hormone (TSH) level

10. Female participants must not be pregnant or breastfeeding.

11. Female participants must either be of non-childbearing potential or using acontraceptive method that is highly effective (with a failure rate of <1% per year),preferably with low user dependency, and agree to continue its use for at least 30days after the last dose of study medication.

12. Male participants must agree to refrain from donating sperm and agree to remainabstinent from heterosexual intercourse or to use a male condom with female partnerswho are on an additional highly effective contraceptive method, both during thestudy and for at least 30 days after the last dose of study medication.

13. Are willing to refrain from any alcohol and nicotine-containing product use duringthe 24 hours prior to each MWT visit.

14. Are willing to refrain from any caffeine use on the day of the MWT visits.

15. Are willing and able to comply with the study requirements.

Exclusion Criteria:

1. History or presence of any acutely unstable medical condition, behavioral orpsychiatric disorder, or surgical history that could affect the safety of theparticipant or interfere with study efficacy, safety, or the ability of theparticipant to complete the trial based on the judgment of the investigator.

2. Presence of renal impairment or calculated creatinine clearance < 60 mL/min.

3. Laboratory value(s) outside the laboratory reference range that is considered to beclinically significant by the investigator (clinical chemistry, hematology, andurinalysis; see Appendix II).

4. Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication forat least 3 months prior to screening.

5. Clinically significant EKG abnormality in the opinion of the investigator.

6. Presence of significant cardiovascular disease including but not limited to:myocardial infarction within the past year, unstable angina pectoris, symptomaticcongestive heart failure (ACC/AHA stage C or D), revascularization procedures withinthe past year, uncontrolled atrial fibrillation, ventricular cardiac arrhythmiasrequiring automatic implantable cardioverter defibrillator or medication therapy,uncontrolled hypertension, systolic blood pressure ≥ 155 mmHg or diastolic bloodpressure ≥ 95 mmHg (at Screening or Baseline), or any history of cardiovasculardisease or any significant cardiovascular condition that in the investigator'sopinion may jeopardize participant safety in the study.

7. History of bariatric surgery within the past year or a history of any gastric bypassprocedure.

8. Use of an MAOI in the past 14 days or five half-lives (whichever is longer) prior tothe Baseline Visit, or plans to use an MAOI during the study.

9. Pregnant or intention to become pregnant.

10. Breast-feeding or plans to breastfeed.

11. On long-term sick leave or with no history of work in the last 12 months

12. Diagnosis with sleep disorder (regardless of treatment status) other than SWDincluding: OSA, PLMD, other circadian rhythm sleep disorders, narcolepsy, or RLSdetermined by a previous sleep-lab diagnosis or during the home sleep test.

13. History of excessive caffeine use or anticipated excessive use (>600mg/day) duringthe study.

14. Use of any OTC or prescription medications that could affect the evaluation of EDSwithin a time period prior to the Baseline visit corresponding to at least 5half-lives of the drug(s) or planned use of such drug(s) at some point throughoutthe duration of the treatment period. Examples of excluded medications include OTCsleep aids, stimulants (e.g. methylphenidate, amphetamines, modafinil, andarmodafinil), sodium oxybate, pemoline, pitolisant, bupropion, trazodone,vortioxetine, duloxetine, tricyclic antidepressants, hypnotics, benzodiazepines,barbiturates, and opioids.

15. Received an investigational drug in the past 30 days or 5 half-lives (whichever islonger) prior to the Baseline visit or plans to use an investigational drug (otherthan the study drug) during the study.

16. History or presence of bipolar disorder, bipolar-related disorders, schizophrenia,schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5criteria.

17. Current or recent (within the past 2 years) diagnosis of a moderate or severesubstance use disorder (excluding caffeine) according to DSM-5 criteria. Nicotineuse disorder is exclusionary only if it has an effect on sleep (i.e., a participantwho routinely awakens at night to smoke) or will interfere with study compliance.

18. Current, recent (within the past 2 years), or seeking treatment for asubstance-related disorder.

19. Positive urine drug screen (UDS) for opiates, phencyclidine (PCP), cocaine,cannabinoid (THC), or amphetamines at Screening or at any point throughout theduration of the study, except for a prescribed drug (e.g., amphetamine) atScreening.

20. History of regular heavy use of tetrahydrocannabinol containing products.Recreational users of cannabis may be repeat UDS tested once during the Screeningperiod. If this is negative, the participant may be allowed to enter the study.

21. Positive alcohol test at Screening. Binge drinking (5 or more drinks per day formen, 4 or more drinks per day for women) within the past month.

22. History of PKU or history of hypersensitivity to phenylalanine-derived products.

23. Previous exposure to solriamfetol (JZP-110, ADX-N05, R228060, or YKP-10A).