Lemborexant for the Treatment of Residual Insomnia in Major Depressive Disorder (MDD)

NCT06843187 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 24-13368425v4
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if Lemborexant works to treat residual insomnia in adults with depression that is being treated. It will also learn about how practical, tolerable, and effective Lemborexant is. The main questions it aims to answer are:

• Does Lemborexant help participants improve sleep and reduce insomnia symptoms?
• How practical is it to use Lemborexant (how many participants join, drop out, and follow the study rules)? How do participants feel about using it (based on surveys and interviews)? Researchers will compare Lemborexant to a placebo (a look-alike substance that contains no drug) to see if Lemborexant works to treat residual insomnia in adequately treated major depressive disorder. Participants will:
• Take Lemborexant or a placebo every day for 6 weeks (2 weeks at 5 mg then 4 weeks at 10 mg)
• Complete clinical assessments and in-person study visits
• Maintain a digital sleep diary and complete daily and weekly self-report ecological momentary assessments (EMAs)
• Use a wearable device which will be used to collect and monitor physiological data

Conditions

Major Depressive Disorder(MDD); Insomnia Comorbid to Psychiatric Disorder

Keywords

Lemborexant; Residual Insomnia; Major depressive disorder (MDD); Ecological momentary assessments (EMA); Wearable devices; Remote measurement-based care; Randomized controlled trial; Digital health monitoring; Feasibility trial; Pilot study; Placebo-controlled

Outcome Measures

Primary Outcomes (2)

• Feasibility Outcomes

  Feasibility will be measured by the recruitment rate, withdrawal rate, data completion rate, and adherence rate. Recruitment rate will be quantified by the percentage of eligible participants enrolled relative to the number of participants contacted. Feasibility will be marked as a minimum of 1-2 participants enrolled per month. Withdrawal/dropout rate will be quantified by the percentage of participants who drop out of the study. The upper limit of the 95% confidence interval (CI) for dropout rate should not exceed 20%. Adherence and data completion will bhe proportion of participants who strictly follow the study protocol (the "per-protocol group") will be estimated with a 95% CI. This includes adherence to treatment (taking the medication correctly for six weeks), study completion (attending all required visits), and providing complete data. To be considered feasible, the lower limit of this 95% CI must be greater than 80%.

  13 weeks

• Tolerability Outcomes

  Tolerability will be measured by the frequency and nature of adverse events and medication adherence (i.e., missed dosage).

  10 weeks

Secondary Outcomes (9)

• Preliminary Clinical Parameters

  6 weeks

• Within-person Correlations

  10 weeks

• Standard Deviation

  13 weeks

• Change in Physiological Biometrics (Oura Ring Metrics)

  13 weeks

• Patient Health Questionnaire-9 (PHQ-9)

  13 weeks

Other Outcomes (1)

• Patient Perspectives

  13 weeks

Study Arms (2)

Lemborexant

EXPERIMENTAL

Participants will take a 5 mg pill of lemborexant daily for two weeks, followed by a dosage increase to 10 mg daily for the next four weeks (6 weeks total).

Drug: Lemborexant

Placebo

PLACEBO COMPARATOR

Participants will take a 5 mg of placebo pill daily for 2 weeks then 10 mg daily for 4 weeks (total of 6 weeks).

Other: Placebo

Interventions

Lemborexant DRUG

Dayvigo (lemborexant compound) is an orexin antagonist that acts on the arousal and sleep neural networks of the brain to regulate sleep-wake cycles and is used in the treatment of insomnia characterized by difficulties with sleep.

Also known as: Dayvigo

Lemborexant

Placebo OTHER

The placebo is an inactive sugar pill that looks and tastes identical to the lemborexant pill.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 (inclusive), with a self-reported body mass index (BMI) between 19 and 35 kg/m2 (inclusive).
• Meet criteria for MDD without psychotic symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and currently in a MDE as confirmed by the MINI International Neuropsychiatric Interview (MINI).
• Have not failed more than 2 trials of antidepressant treatments in the current MDE, and have a history of adequate response (clinical outcome rating score of 1 or 2) to at least 1 antidepressant treatment during the current MDE as determined by the Antidepressant Treatment History Form-Short Form (ATHF-SF).
• Are outpatients.
• Did not take non-psychotropic or non-central nervous system (CNS) medications suspected to affect sleep-wake function for at least 4 weeks before starting the study.
• At screening visit 1, self-reported subjective total sleep time (sTST) ≤ 6.5 hours, subjective sleep onset latency (sSOL) ≥ 30 mins, and subjective wake time after sleep onset (sWASO) ≥ 45 mins per night at least three times per week 1 month prior to screening.
• At screening visit 1, self-reported regular time spent in bed, either sleeping or trying to sleep must be between 7 and 10 hours, inclusive.
• At screening visit 1, self-reported regular bedtime (i.e., the time the participant gets in bed) between 21:00 and 01:00 and regular wake time (i.e., the time participant wakes and does not go back to sleep) between 05:00 and 10:00.
• At screening visit 2, confirmation of current insomnia symptoms as determined from responses on the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL ≥ 30 mins on at least 3 of the 7 nights and/or sWASO ≥ 45 mins on at least 3 of the 7 nights.
• At screening visit 2, confirmation of sufficient duration of time spent in bed, as determined from responses on the Sleep Diary on the 7 most recent mornings before the visit, such that there are no more than 2 nights with time spent in bed of duration \< 7 hours or \> 10 hours.
• At screening visit 2, confirmation of regular bedtime (i.e., the time the participant gets in bed) between 21:00 and 01:00 on at least 5 of the 7 preceding nights, and regular wake time (i.e., the time the participant wakes and does not go back to sleep) between 05:00 and 10:00 on at least 5 of the 7 preceding nights.
• Are able to understand and comply with the requirements of the study, as judged by the investigator(s).
• Provide written informed consent before initiation of any study-related procedures.
• Own a smartphone and have reliable access to the internet and a browser on which to complete questionnaires.

You may not qualify if:

• Previously participated in any clinical trial of lemborexant.
• Have any known sensitivity to lemborexant or their excipients.
• Failed treatment with an appropriate dose or adequate duration of dual orexin receptor antagonist drugs (efficacy or safety), in the opinion of the investigator.
• Women who are pregnant or lactating (documented by a positive beta-human chorionic gonadotropin \[beta-hCG\] or human chorionic gonadotropin \[hCG\] urine test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG or hCG).
• Women who are not using any of the following approved and effective method of contraception or family planning during the study: Combined estrogen- and progestogen-containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and litigation, vasectomized partner, sexual abstinence, or two forms of contraception with any barrier method or oral hormones (e.g., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom).
• If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions or the therapeutic focus 4 weeks before screening and the entire duration of participation.
• Unable to keep any current psychiatric medications unchanged for 4 weeks before screening and for the entire duration of participation in the study.
• Have active suicidal intent as determined by a score of 3 (severe suicidality with a clear plan and/or intent) or 4 (very severe: suicidal attempts) on item #3 on the HAM-D-17.
• Have had a course of electroconvulsive therapy or intravenous ketamine therapy in the current episode or any previous episode.
• According to medical history, have had insomnia associated with another sleep disorder or have a history of any condition that impacted or was likely to impact sleep, including any lifetime diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement (REM) behaviour disorder, or narcolepsy.
• Habitual naps during the day more than 3 times/week.
• Transmeridian travel across more than 3 time zones in the 2 weeks before screening, or between screening and study baseline, or plans to travel across more than 3 time zones during the study.
• Used any modality of treatment for insomnia, including cognitive-behavioural therapy or cannabis within 2 weeks before screening.
• Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or habitually consumes caffeine-containing beverages after 18:00.
• Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males).

Sponsors & Collaborators

• Unity Health Toronto: lead
• University of Toronto: collaborator
• Centre for Addiction and Mental Health: collaborator
• Toronto Metropolitan University: collaborator

Study Sites (1)

St. Michael's Hospital, Unity Health Toronto

Toronto, Ontario, M5B 1W8, Canada

Location

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MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

lemborexant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Venkat Bhat, MD, MSc

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Venkat Bhat, MD, MSc

CONTACT

416-360-4000; venkat.bhat@unityhealth.to

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Data analyst and co-investigators
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A double-blind, randomized placebo-controlled pilot trial will be conducted with 30 adults with MDD and residual insomnia. Participants will be randomized to one of two intervention arms (2:1 allocation): lemborexant (experimental group; n = 20) or placebo (control group; n = 10). There will be a 3-week baseline period prior to the 6-week intervention period (lemborexant or a placebo pill for 2 weeks at 5 mg then 4 weeks at 10 mg) and 4-week follow-up period with weekly clinical assessments. Participants will complete a daily digital sleep diary and frequent EMAs on a web-based survey platform as well as passive digital health monitoring via a wearable device. Semi-structured exit interviews will be completed at the end of the study.

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: February 24, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 24, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)