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

NCT04788953 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 2021-P-000509
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Excessive Sleepiness; Shift-work Disorder

Keywords

Excessive Daytime Sleepiness; Early Morning Shift Work

Outcome Measures

Primary Outcomes (1)

• 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 (3)

• Change in Karolinska Sleepiness Scale Score

  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

  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

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

Other Outcomes (6)

• Change in Overall Work Impairment Score From the Work Productivity and Activity Impairment Questionnaire

  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

  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

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

Study Arms (2)

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

Interventions

Solriamfetol Oral Tablet DRUG

The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019

Also known as: Sunosi

Solriamfetol (Sunosi)

Placebo DRUG

Control subjects will receive placebo tablets for oral use.

Control

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Charles A. Czeisler, PhD, MD: lead
• Axsome Therapeutics, Inc.: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 41590992 DERIVED

MeSH Terms

Conditions

Disorders of Excessive Somnolence

Interventions

solriamfetol

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Results Point of Contact

• Title: Dr. Kirsi-Marja Zitting
• Organization: Brigham and Women's Hospital

kzitting@bwh.harvard.edu

617-525-8339

Study Officials

• Charles A Czeisler, PhD,MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Baldino Professor of Sleep Medicine, Division Chief

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 9, 2021
• Study Start: July 21, 2021
• Primary Completion: April 6, 2024
• Study Completion: April 19, 2024
• Last Updated: September 24, 2025
• Results First Posted: September 24, 2025

Record last verified: 2025-09

Locations

US (1)