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

Excessive Sleepiness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04788953
• Other study ID #: 2021-P-000509
• Status: Recruiting
• Phase: Phase 4
• Start date: July 21, 2021
• Est. completion date: November 30, 2024

Study information

• Verified date: February 2024
• Source: Brigham and Women's Hospital
• Contact: Study Coordinator
• Phone: 617-525-8657
• Email: edsresearchstudy[@]partners.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: November 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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).

Related Conditions & MeSH terms

• Disorders of Excessive Somnolence
• Excessive Sleepiness
• Shift-work Disorder
• Sleepiness

Intervention

Drug:
• Solriamfetol Oral Tablet
The administered drug is SUNOSI (solriamfetol) tablets for oral use. Initial U.S. Approval: 2019
• Placebo
Control subjects will receive placebo tablets for oral use.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Charles A. Czeisler, PhD, MD	Axsome Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Work Function and Daily Activity	Demonstrate improvement in work function and daily activity in early-morning shift workers after treatment with solriamfetol, as assessed by Work Productivity and Activity Impairment-Specific Health Problem questionnaire (WPAI-SHP; Reilly et al., 1993; Emsellem et al., 2020).	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Other	Change in Subjective Global Functioning on FOSQ-10	Demonstrate improvement in subjective global functioning, as assessed with Functional Outcomes of Sleep Questionnaire (FOSQ-10; Chasens et al., 2009), in early-morning shift workers after treatment with solriamfetol.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Other	Change in Subjective Global Functioning on SDS	Demonstrate improvement in subjective global functioning, as assessed with Sheehan Disability Scale (SDS; Sheehan & Sheehan, 2008), in early-morning shift workers after treatment with solriamfetol.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Other	No Change in Total Sleep Time	Demonstrate that early-morning shift workers who are treated with solriamfetol do not show significant reduction in objective Total Sleep Time (Actigraphy-TST).	Baseline Segment (Weeks 1-2 of Study) and Treatment Segment 2 (Weeks 5-6 of Study)
Other	No Change in Sleep Disturbances	Demonstrate that early-morning shift workers who are treated with solriamfetol do not show significant increases in sleep disturbances (Actigraphy-Fragmentation Index).	Baseline Segment (Weeks 1-2 of Study) and Treatment Segment 2 (Weeks 5-6 of Study)
Other	Change in Excessive Daytime Sleepiness	Demonstrate improvement of subjective sleepiness (decreased score on modified Epworth Sleepiness Scale (ESS, Johns, 1990, 1997) in early-morning shift workers after treatment with solriamfetol.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Primary	Change in Objective Sleepiness	Demonstrate improvement of objective sleepiness (assessed with a Maintenance Wakefulness Test (MWT)) in early-morning shift workers after treatment with solriamfetol.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Secondary	Change in Subjective Sleepiness on KSS	Demonstrate improvement of subjective sleepiness [assessed with a Karolinska Sleepiness Scale (KSS, Åkerstedt & Gillberg, 1990) in early-morning shift workers after treatment with solriamfetol.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Secondary	Change in Clinician's Global Impression	Demonstrate improvement of clinician's global impression [assessed with Clinical Global Impression- CGI-Change (Guy, 1976)] in early-morning shift workers after treatment with solriamfetol.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)
Secondary	Change in Patient's Global Impression of Change	Demonstrate improvement of Patient's Global Impression of Change (Guy, 1976) after treatment with solriamfetol in early-morning shift workers.	Study Visit 2 (Baseline Visit) and Study Visit 5 (Final Visit, 6 weeks after Baseline)