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

In this research study the investigators want to learn more about whether the medication Solriamfetol improves daytime sleepiness in workers who start work at very early times (between 3 and 6am).

Study Overview

• Status: Terminated
• Conditions: Excessive Sleepiness; Shift-work Disorder
• Intervention / Treatment: Drug: Solriamfetol Oral Tablet; Drug: Placebo

Detailed Description

Shift work has become increasingly common as the 24/7 global society has required more and more workers to do their jobs at irregular hours. According to the National Health Interview Survey in 2010, approximately 28.7% of the American workforce is engaged in work outside a regular day shift (outside 7 AM-to 6 PM). Working irregular hours poses a serious threat to the shift worker's physical, mental, and psychosocial health due to circadian misalignment and misplaced sleep. The most severe problems faced by shift workers are sleep disturbances and excessive sleepiness. The disruptions caused by shift work are recognized as a circadian rhythm sleep disorder in the International Classification of Sleep Disorders, 3rd Edition, and is called Shift Work Disorder [SWD]. SWD is characterized by excessive sleepiness (ES) during wakefulness, accompanied by a reduction of total sleep time and/or insomnia. Several studies have shown that 10-43% of shift workers are diagnosed with SWD, dependent on the criteria used.

Studies have shown that wake promoting agents can be used to treat ES in shift workers, ranging from caffeine to prescription pharmacological agents. Current Food and Drug Administration (FDA)-approved options for SWD patients with ES are modafinil and armodafinil. A three-month, double-blind trial of 209 randomized SWD patients showed that modafinil improves wakefulness and the ability to sustain attention working night shifts without negatively affecting daytime sleep. Furthermore, SWD patients who received modafinil had an improvement in clinical symptoms, reduced levels of sleepiness during night shift and during commute home, and proportionally fewer patients reported motor vehicle accidents or near accidents while commuting home. Czeisler and colleagues also performed a 12-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study, which showed that armodafinil was well-tolerated and improved clinical conditions, wakefulness, attention and memory during night shifts in SWD patients without jeopardizing daytime sleep and reduced sleepiness during the commute home.

All these previous studies were described in SWD patients working night shifts, yet approximately 3 times as many individuals work shifts that start in the early morning compared with those who work night shifts. These early-morning shift workers are a unique, high-risk group because their early work start times (3:00 AM to 6:00 AM) require the workers to wake up in the middle of the night, close to their circadian nadir, resulting in curtailed sleep and commuting to work during times of high sleepiness. Previous research has shown that early-morning shift starts in particular are associated with increased sleepiness. To the investigators' knowledge, no studies have addressed the use of wake promoting agents for ES in early-morning shift workers.

In this clinical trial, the investigators will test whether Solriamfetol (SUNOSITM), a drug approved for the treatment of ES in patients with obstructive sleep apnea (OSA) and narcolepsy, is effective in: (1) decreasing sleepiness without reducing sleep duration or sleep quality; (2) improving work functioning; and (3) improving quality of life in early-morning shift workers diagnosed with ES associated with SWD.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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-6 AM, 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 SWD symptoms confirmed by clinician) with excessive sleepiness (as measured by the modified 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 a contraceptive 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 30 days after the last dose of study medication.
12. Male participants must agree to refrain from donating sperm and agree to remain abstinent from heterosexual intercourse or to use a male condom with female partners who are on an additional highly effective contraceptive method, both during the study 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 during the 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 or psychiatric disorder, or surgical history that could affect the safety of the participant or interfere with study efficacy, safety, or the ability of the participant 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 be clinically significant by the investigator (clinical chemistry, hematology, and urinalysis; see Appendix II).
4. Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication for at 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, symptomatic congestive heart failure (ACC/AHA stage C or D), revascularization procedures within the past year, uncontrolled atrial fibrillation, ventricular cardiac arrhythmias requiring automatic implantable cardioverter defibrillator or medication therapy, uncontrolled hypertension, systolic blood pressure ≥ 155 mmHg or diastolic blood pressure ≥ 95 mmHg (at Screening or Baseline), or any history of cardiovascular disease or any significant cardiovascular condition that in the investigator's opinion may jeopardize participant safety in the study.
7. History of bariatric surgery within the past year or a history of any gastric bypass procedure.
8. Use of an MAOI in the past 14 days or five half-lives (whichever is longer) prior to the 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 SWD including: OSA, PLMD, other circadian rhythm sleep disorders, narcolepsy, or RLS determined by a previous sleep-lab diagnosis or during the home sleep test.
13. History of excessive caffeine use or anticipated excessive use (>600mg/day) during the study.
14. Use of any OTC or prescription 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 of such drug(s) at some point throughout the duration of the treatment period. Examples of excluded medications include OTC sleep aids, stimulants (e.g. methylphenidate, amphetamines, modafinil, and armodafinil), 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 is longer) prior to the Baseline visit or plans to use an investigational drug (other than 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-5 criteria.
17. Current or recent (within the past 2 years) diagnosis of a moderate or severe substance use disorder (excluding caffeine) according to DSM-5 criteria. Nicotine use disorder is exclusionary only if it has an effect on sleep (i.e., a participant who routinely awakens at night to smoke) or will interfere with study compliance.
18. Current, recent (within the past 2 years), or seeking treatment for a substance-related disorder.
19. Positive urine drug screen (UDS) for opiates, phencyclidine (PCP), cocaine, cannabinoid (THC), or amphetamines at Screening or at any point throughout the duration of the study, except for a prescribed drug (e.g., amphetamine) at Screening.
20. History of regular heavy use of tetrahydrocannabinol containing products. Recreational users of cannabis may be repeat UDS tested once during the Screening period. 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 for men, 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Solriamfetol (Sunosi); Participants will start at 75 mg and take that dose for 3 consecutive days. Participants will take their first 75mg dose on an early morning work day and take the next two 75 mg doses upon awakening regardless of their work schedule. They will then move to 150mg on the next early morning work day and for all subsequent early morning shift work days. The drug/placebo will be taken orally within 30 minutes after awakening, before the start of each early morning shift. Prior to the end of study of visit (Visit 5), drug will be taken at home within 30 minutes of awakening.	Drug: Solriamfetol Oral Tablet; The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019; Other Names: Sunosi
Placebo Comparator: Control; Participants randomized into the Control arm will receive a placebo	Drug: Placebo; Control subjects will receive placebo tablets for oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sleep Latency	Sleep latency was assessed with a Maintenance Wakefulness Test (MWT) at Visit 2 (Baseline) and again at Visit 5 (End-of-Treatment). The MWT started ~2 hours after participant's usual wake time and consisted of four 40-minute trials (2, 4, 6, and 8 hours after usual wake time). Participants were fitted with polysomnography (PSG) and instructed to stay awake. Each trial was monitored and the trial was ended after PSG-sleep occurred or after 40 minutes if no sleep occurred. Sleep latency (in minutes) was calculated as the time between trial start time and sleep onset time. Change in mean sleep latency (i.e., averaged sleep latency across the four trials) from Visit 2 to Visit 5 was calculated for each participant.	Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Karolinska Sleepiness Scale Score	Subjective sleepiness was assessed with a Karolinska Sleepiness Scale (KSS, Åkerstedt & Gillberg, 1990). The KSS was administered to the participant ~5 minutes before the start of each four MWT trial at Visit 5 (Baseline) and again at Visit 5 (End-of-Treatment). The KSS scores range from 1 (very alert) to 9 (very sleepy), with higher scores indicating higher levels of sleepiness. Change in the mean KSS score (i.e., averaged score across the four trials) from Visit 2 to Visit 5 was calculated for each participant.	Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)
Change in Clinician's Global Impression of Change Score	Overall change in participant's clinical condition was assessed with a Clinician's Global Impression of Change scale (CGI-Change, Guy, 1976). The CGI-change was conducted at Visit 5 (End-of-Treatment) by a study doctor who rated the participant. The scores range from 1 (very much improved) to 7 (very much worse), with lower scores indicating improved condition. Data were dichotomized such that scores 1-3 (very much improved, much improved, minimally improved) were considered to indicate improvement and scores 4-7 (no change, minimally worse, much worse, very much worse) were considered to indicate no improvement. Improvement was calculate as the percentage of participants in each group who reported improved scores.	Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)
Change in Patient's Global Impression of Change Score	Participant's overall perception of change in their condition (i.e., excessive sleepiness) was assessed with a Patient's Global Impression of Change scale (PGI-Change, Guy, 1976). The PGI-C was administered to the participant at Visit 5 (End-of-Treatment). The scores ranged from 1 (no change or worse) to 7 (a great deal better), with higher scores indicating improved condition. Data were dichotomized such that scores 1-2 (no change or worse, hardly any change) were considered to indicate no improvement, and scores 3-7 (a little better, somewhat better, moderately better, better, a great deal better) were considered to indicate improvement.	Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Overall Work Impairment Score From the Work Productivity and Activity Impairment Questionnaire	Work impairment was assessed with a Work Productivity and Activity Impairment-Specific Health Problem questionnaire (WPAI-SHP, Reilly et al., 1993; Emsellem et al., 2020), with excessive sleepiness as the specific health problem. The WPAI-SHP questionnaire was administered to the participant at Visit 2 (Baseline) and again at Visit 5 (End-of-Treatment). Overall work impairment score, which ranges from 0 to 100 with higher score indicating more impairment, was calculated from the WPAI-SHP subscales according to the WPAI scoring manual by Dr. Reilly. Change in the overall work impairment score from Visit 2 to Visit 5 was calculated for each participant.	Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)
Change in Functional Outcomes of Sleep Questionnaire Score	Subjective global functioning was assessed with the short version of the Functional Outcomes of Sleep Questionnaire (FOSQ-10; Chasens et al., 2009). The FOSQ-10 was administered to the participant at Visit 2 (Baseline) and again at Visit 5 (End-of-Treatment). The FOSQ-10 consists of ten subscales with each subscale ranging from 1 (extreme difficulty) to 4 (no difficulty). The FOSQ-10 total score, which was calculated as the mean-weighted item score computed from the ten subscales, ranges from 5 to 20 with higher scores indicating less functional impairment. Change in FOSQ-10 total score from Visit 2 to Visit 5 was calculated for each participant.	Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)
Change in Sheehan Disability Scale Score	The impact of excessive sleepiness on subjective global functioning was assessed with a Sheehan Disability Scale (SDS; Sheehan & Sheehan, 2008). The questionnaire was administered to the participants at Visit 2 (Baseline) and again at Visit 5 (End-of-Treatment). The SDS consists of five subscales, with the scores for the three subscales (work, social, and family life) that are used for calculating the total score ranging from 0 (not at all impacted) to 10 (extremely impacted). The SDS total score, which was calculated as the sum of the three subscale scores, ranges from 0 to 30 with higher scores indicating greater functional impairment. Change in the SDS total score from Visit 2 to Visit 5 was calculated for each participant. which ranges from 0 to 30,	Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)
Change in Total Sleep Time	Total Sleep Time (TST) was assessed with actigraphy. Participants wore a wrist activity monitor throughout the study (i.e., 2 weeks of baseline and 4 weeks of treatment). The actigraphy data from the main sleep periods were manually scored in 30-second epochs, and TST was calculated in minutes for each study day. Change in TST from baseline to treatment was calculated for each participant.	Baseline Segment (2 weeks) and Treatment Segment (4 weeks)
Change in Sleep Fragmentation Index	Sleep disturbances were assessed with actigraphy-derived fragmentation index. Participants wore a wrist activity monitor throughout the study (i.e., 2 weeks of baseline and 4 weeks of treatment). The actigraphy data from the main sleep periods were manually scored in 30-second epochs in the MotioWare software (CamNtech, Cambridge, UK). MotionWare defines the fragmentation index as the sum of the percentages of mobile time and immobile bouts immobile bouts below or equal to 1 minute during the sleep period, which is a unitless measure. Change in fragmentation index from baseline to treatment was calculated for each participant.	Baseline Segment (2 Weeks) and Treatment Segment (4 Weeks)
Change in Epworth Sleepiness Scale Score	Subjective sleepiness was assessed with a modified Epworth Sleepiness Scale (ESS, Johns, 1990, 1997). The ESS was administered to the participant at Visit 2 (Baseline) and again at Visit 5 (End-of-Treatment). The ESS consists of eight subscales with each subscale ranging from 0 (never doze) to 3 (high change to doze off). The ESS total score, which was calculated as the sum of the eight subscalescores, ranges from 0 (normal levels of sleepiness) to 24 (severe excessive sleepiness) with higher scores indcating higher levels of sleepiness. Change in the ESS total score from Visit 2 to Visit 5 was calculated for each participant. total score, which ranges from 0 to 24 (0=normal level of sleepiness, 24=severe excessive sleepiness), was calculated by summing the scores from the eight subscales. Change in ESS total score from Visit 2 to Visit 5 was calculated for each participant.	Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End of Treatment Visit after 4 weeks on solriamfetol or placebo)

Collaborators and Investigators

• Sponsor: Charles A. Czeisler, PhD, MD
• Collaborators: Axsome Therapeutics, Inc.
• Investigators: Principal Investigator: Charles A Czeisler, PhD,MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Actual): April 6, 2024
• Study Completion (Actual): April 19, 2024

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Excessive Daytime Sleepiness; Early Morning Shift Work
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Disorders of Excessive Somnolence; solriamfetol
• Other Study ID Numbers: 2021-P-000509

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No