Clinical Trial of Solriamfetol for Excessive Sleepiness R... | NCT04788953

Name	Class
Axsome Therapeutics, Inc.	INDUSTRY

Description Module

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.

Label	Type	Description	Intervention Names
Solriamfetol (Sunosi)	Experimental	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
Control	Placebo Comparator	Participants randomized into the Control arm will receive a placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Solriamfetol Oral Tablet	Drug	The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019	Solriamfetol (Sunosi)

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Other Outcomes

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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Men and women
Ages 18 to 64 years
Early-morning shift workers with a fixed work schedule (start times between 3 AM-6 AM, for at least 3 days per week)
≥ 20 work hours per week, 6-hour to 12-hour shifts
≥ 3-month history of working early morning shifts prior to the study
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
Baseline MWT average sleep latency <20 minutes on the first 4 scheduled naps
Body mass index 18.5 to 45 kg/m2
Normal thyroid stimulating hormone (TSH) level
Female participants must not be pregnant or breastfeeding.
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.
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.
Are willing to refrain from any alcohol and nicotine-containing product use during the 24 hours prior to each MWT visit.
Are willing to refrain from any caffeine use on the day of the MWT visits.
Are willing and able to comply with the study requirements.

Exclusion Criteria:

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.
Presence of renal impairment or calculated creatinine clearance < 60 mL/min.
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).
Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication for at least 3 months prior to screening.
Clinically significant EKG abnormality in the opinion of the investigator.
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.
History of bariatric surgery within the past year or a history of any gastric bypass procedure.
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.
Pregnant or intention to become pregnant.
Breast-feeding or plans to breastfeed.
On long-term sick leave or with no history of work in the last 12 months
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.
History of excessive caffeine use or anticipated excessive use (>600mg/day) during the study.
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.
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.
History or presence of bipolar disorder, bipolar-related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria.
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.
Current, recent (within the past 2 years), or seeking treatment for a substance-related disorder.
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.
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.
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.
History of PKU or history of hypersensitivity to phenylalanine-derived products.
Previous exposure to solriamfetol (JZP-110, ADX-N05, R228060, or YKP-10A).

Name	Affiliation	Role
Charles A Czeisler, PhD,MD	Brigham and Women's Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Brigham and Women's Hospital		Boston	Massachusetts	02115	United States

PubMed Identifier	Type	Citation	Retractions
41590992	Derived	Zitting KM, Gilmore KR, Lockyer BJ, Leary EB, Wang W, Issa NC, Quan SF, Williams JS, Duffy JF, Czeisler CA. Solriamfetol for Excessive Sleepiness in Early-Morning Shift Work Disorder. NEJM Evid. 2026 Feb;5(2):EVIDoa2500190. doi: 10.1056/EVIDoa2500190. Epub 2026 Jan 27.

ID	Title	Description
FG000	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. Solriamfetol Oral Tablet: The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019
FG001	Control	Participants randomized into the Control arm will receive a placebo. Placebo: Control subjects will receive placebo tablets for oral use.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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. Solriamfetol Oral Tablet: The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Data were analyzed for all participants who completed the study.

Posted

Least Squares Mean

95% Confidence Interval

minutes

Study Visit 2 (i.e., Baseline Visit) and Study Visit 5 (i.e., End-of-Treatment Visit after 4 weeks on solriamfetol or placebo)

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. Solriamfetol Oral Tablet: The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 16, 2023	Apr 14, 2025	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Jan 13, 2025	Apr 14, 2025	ICF_001.pdf

ID	Term
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases