The Effects of Lemborexant on the Ability to Sleep During Daytime

The Effects of Lemborexant on the Ability to Sleep During Daytime: A Feasibility Study to Evaluate the Potential of Lemborexant to Treat Shift Work Disorder

This study aim to evaluate whether a dose of 5 mg of lemborexant, as compared to a placebo, may improve daytime recovery sleep, without producing lingering sleepiness during wakefulness, using a 3-day simulated night shift protocol in the lab under constant monitoring.

Study Overview

• Status: Recruiting
• Conditions: Shift-Work Sleep Disorder
• Intervention / Treatment: Drug: Lemborexant 5 MG [Dayvigo]; Other: Matching Placebo

Detailed Description

After being informed about the study and potential risks, all patients giving written informed conset will undergo 2 screening visits to determine eligibility for study entry. Selected participants will then stay twice in the lab (active treatment condition and placebo condition), each visit lasting approximately 4 days. Participants will stay awake across the night and sleep during the day. Only the experimental condition will be different between the two visits (lemborexant or placebo). These experimental visits will be double-blind, in counterbalanced order and separated by an interval of at least 2 weeks (washout period).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alex Desautels, M.D., Ph.D.; Phone Number: 514-338-2692; Email: alex.desautels@umontreal.ca
• Study Contact Backup: Name: Veronique Daneault, M.Sc, Ph.D.; Phone Number: 438-224-2474; Email: veronique.daneault.cnmtl@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4J 1C5
      • Recruiting
      • CIUSSS du Nord de l'ile de Montreal (CIUSSS-NIM) - Hôpital du Sacré-Cœur de Montréal (HSCM)
      • Contact: Alex Desautels, M.D., Ph.D.; Phone Number: 514-338-2692; Email: alex.desautels@umontreal.ca
      • Contact: Véronique Daneault, M.Sc., Ph.D.; Phone Number: 438-224-2474; Email: veronique.daneault.cnmtl@ssss.gouv.qc.ca
      • Principal Investigator: Alex Desautels, M.D., Ph.D.
      • Sub-Investigator: Julie Carrier, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants must fulfill all of the following inclusion criteria to be eligible for inclusion in this study:

1. Men or women aged between 30 and 60 years, inclusive
2. Be willing and able to give informed consent for study participation
3. Participants must not have done shiftwork in the past year
4. Normal vital signs values are: oral body temperature between 36.1 and 37.5 ºC (95 and 99.5 °F), supine SBP between 90 and 140 mmHg inclusive; supine DBP between 55 and 90 mmHg inclusive; heart rate between 50 and 100 bpm inclusive.
5. Be willing to comply with all study requirements and procedures for the duration of the study, including refraining from consuming alcohol 48 hours prior to each experimental visit and grapefruit products (juice or fruit itself), Seville orange, lime, pomelo, carambola and pomegranate during all the duration of the study (from Visit 1 to Visit 4).

6. Women who:

   • Are postmenopausal, with amenorrhea for at least 1 year before the screening visit, OR
   • Are surgically sterile, OR
   • If of childbearing potential agree to practice effective double barrier methods of contraception, from the time of the signing of informed consent through the last dose of study drug and for 30 days after dosing stops (1 ovulatory cycle), or agree to completely abstain from intercourse.

   Men with women partners of childbearing potential are also expected to practice effective barrier methods of contraception from the time of signing informed consent through the last dose of study drug and for 30 days after dosing stops.

7. Self-reported bedtime was between 9 pm and midnight on 4-7 nights per week.

Exclusion Criteria:

Participants must not meet any of the following exclusion criteria:

1. Body mass index > 32 as calculated from the participant's height (m) and weight (kg); weight (kg)/square height (m²)
2. Presence of a sleep disorder, such as a diagnosis of insomnia, narcolepsy, sleep paralysis, active somnambulism (history of childhood somnambulism is accepted), hypnagogic/ hypnopompic hallucinations, and REM behavior disorder, will be excluded based on the clinical interview. For sleep apnea syndrome, an apnea-hypopnea index > 15 per hour of sleep on the first screening night will be used as an exclusion criterion. For periodic limb movement disorder, an index of periodic limb movements during sleep associated with an arousal > 15 per hour of sleep on the first screening night will be used as an exclusion criterion.
3. History of epilepsy
4. Any previous serious head injury or stroke
5. Any evidence of psychiatric disorder (including Beck Depression Inventory [BDI] ≥ 20 at screening, or a score of 3 on item related to suicidal ideas)
6. Evidence of any clinically significant, or unstable, acute or chronically progressive medical or surgical disorder (including planned medical procedures that may impact sleep), or any condition that may interfere with the absorption, metabolism, distribution, or excretion of the study drug, or may affect the participant's safety
7. Clinically significant and abnormal electrocardiogram (ECG; including QTc ≥ 450 ms for males, 460 ms for females) or a history of cardiovascular disease including poorly controlled hypertension, ischemic heart disease, arrhythmia, or severe heart failure
8. Severe hepatic impairment
9. Positive qualitative urine drug screen (opiates, cocaine, amphetamine, cannabinoids, barbiturates, phencyclidine, benzodiazepines, methadone, propoxyphene) and alcohol test (breathalyzer), at screening and before each experimental visit
10. Current use of medications that are moderate or strong CYP3A4 inhibitors or inducers or CYP2B6 substrates (Appendix 1)
11. Use of any substance with psychotropic effects or properties known to affect sleep/wake, including hypnotics, neuroleptics, opioid derivatives, antihistamines, stimulants, antidepressants, within one week or five half-lives (whichever is longer) prior to PSG screening
12. Use of any over-the-counter sleep medications including tryptophan, valerian root (Valeriana officinalis), kava (Piper methysticum Forst), melatonin, St John's Wort (Hypericum perforatum), Alluna (herbal sleep supplement with valerian root), and hemp within one week or five half-lives (whichever is longer) prior to screening
13. Consumption of xanthine-containing beverages (i.e., tea, coffee, or cola) of more than 5 cups or glasses per day
14. Participation in any other trial within 30 days before the screening visit
15. Any travel across more than one time zone in the month prior to screening at any time during the study
16. Other exclusion criteria based on adverse events (AE) or serious adverse events (SAE) reported in the Investigator Brochure
17. Women who are pregnant, during the study or within one month after the study, or are breastfeeding
18. Individuals may be excluded from participating in the study based on the clinician's judgement.
19. Participants with lactose or galactose intolerance (galactosemia or glucose-galactose malabsorption)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active treatment condition; Lemborexant at a 5mg dose is delivered in a film-coated tablet	Drug: Lemborexant 5 MG [Dayvigo]; Lemborexant 5 mg will be taken orally once per day just prior to initiating laboratory-supervised daytime sleep episodes, for three consecutive days, within a few minutes before going to bed, with at least seven hours remaining before the planned time of awakening.
Placebo Comparator: Placebo condition; Placebo is delivered in a film-coated tablet	Other: Matching Placebo; Matching placebo will be taken orally once per day just prior to initiating laboratory-supervised daytime sleep episodes, for three consecutive days, within a few minutes before going to bed, with at least seven hours remaining before the planned time of awakening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total sleep duration (objective measure)	Assess the efficacy of lemborexant compared to placebo on PSG measured total sleep time (TST) during daytime recovery sleep using the mean data of the second and third daytime sleep episodes in each condition.	during the intervention
Wake after sleep onset (objective measure)	Assess the efficacy of lemborexant compared to placebo on polysomnographically (PSG) measured wake after sleep onset (WASO) during daytime recovery sleep using the mean data of the second and third daytime sleep episodes in each condition	during the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total sleep duration (subjective measure)	Evaluate the participant-reported daytime recovery sleep quality, measured as subjective TST (sTST), under lemborexant in comparison to placebo using the mean data of the second and third daytime sleep episodes in each condition	during the intervention
Wake after sleep onset (subjective measure)	Evaluate the participant-reported daytime recovery sleep quality, measured as subjective WASO (sWASO), under lemborexant in comparison to placebo using the mean data of the second and third daytime sleep episodes in each condition.	during the intervention

Collaborators and Investigators

• Sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Daytime sleep episodes; Polysomnographic recordings; Subjective sleep evaluations; Total sleep time (TST); Wake after sleep onset (WASO)
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Neurologic Manifestations; Occupational Diseases; Chronobiology Disorders; Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Lemborexant
• Other Study ID Numbers: DVG-IIS-M001-1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes