A 12-Week, Open-Label, Multicenter Pilot Study to Evaluate the Effectiveness of Lemborexant in Patients with Insomnia Comorbid with Depressive Episodes

JRCT ID: jRCTs071220037

Registered date:04/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Insomnia comorbid with depressive episodes
• Date of first enrollment: 25/10/2022
• Target sample size: 120
• Study type: Interventional
• Intervention(s): LEM is administered orally once daily just before bedtime. The duration of administration is 12 weeks. In principle, the starting dose of 5 mg/day will be maintained for 4 weeks for all study subjects, the dose can be adjusted up to 10 mg/day at the discretion of the investigator in consideration of efficacy, safety, and tolerability.

Outcome(s)

• Primary Outcome: Change from baseline in ISI total score (7 items) at 4 weeks after LEM treatment in insomnia patients with comorbid depressive episodes.

Secondary Outcome

The following secondary endpoints will be evaluated for all cohorts(2) is BD, LEM Add-on Cohort and BD, LEM Monotherapy Cohort only).
1) The change from baseline in HAM-D-17 total score at 4, 8 and 12 weeks after the start of treatment
-Total score (items 1-17)
-Total score excluding items related to sleep (items 1-3, 7-17)
2) The change from baseline in the Young Mania Rating Scale (YMRS) total score at 4, 8 and 12 weeks after the start of treatment
3) The change from baseline in ISI total score (7 items) at 8 and 12 weeks after the start of treatment
(4) The change from baseline in ISI subdomains at 4, 8 and 12 weeks after the start of treatment
-Total score of items related to severity of insomnia symptoms (items 1-3)
-Total points for items related to the effects of insomnia symptoms (items 4-7)
5) The change from baseline in subjective sleep parameters (sSOL, sWASO, subjective wake episodes, sTST, sSE, sleep quality, next morning carryover and mood) assessed by sleep diary at 4 weeks after the start of treatment
-sSE is defined as the percentage of sTST out of the subjective bedtime recorded by the sleep diary
6) The change from baseline in WHO-DAS 2.0 total score and sub-domain scores (6 domains) at 4, 8 and 12 weeks after the start of treatment
7) Percentage of study subjects in each response category for each item of the PGI-Insomnia at 4, 8, and 12 weeks after the start of treatment
8) Percentage of study subjects who continued LEM after 4, 8, and 12 weeks after the start of treatment
9) Change from baseline in diazepam equivalent of concomitant BZRA at 4, 8 and 12 weeks of treatment

Safety Assessment
Safety and tolerability (incidence of adverse events and side effects) of LEM during the treatment period

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Men and women (outpatients) 18 years of age or older at the time consent is obtained
2) Those who meet the diagnostic criteria for insomnia disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
-The patient has a significant complaint of dissatisfaction with the quantity or quality of sleep despite adequate opportunities for sleep, accompanied by one (or more) of the following symptoms: difficulty falling asleep, mid-wake, or early morning awakening.
-The sleep difficulty occurs at least three times a week.
-The sleep difficulty lasts at least 3 months.
-The sleep disturbance is causing impairment in daytime functioning.
(3) Those who meet the diagnostic criteria for depressive episodes in DSM-5
(4) Those who meet the diagnostic criteria for either major depressive disorder(MDD) or bipolar disorder (BD) in DSM-5
(5) Receiving treatment for depressive episodes for 4 weeks prior to the pretreatment period.
(6) the Hamilton Depression Rating Scale (HAM-D-17) total score of 8 or higher at baseline
(7) Those who are judged by the investigator to have the ability to understand and comply with the content of the clinical research.

Exclude criteria

1) Those with moderate or severe obstructive sleep apnea (OSA)
2) Those with periodic limb movement disorder, restless legs syndrome, or parasomnia
3) Those with comorbidity or history of narcolepsy or cataplexy
4) Those with manic or hypomanic episodes within 4 weeks prior to the start of the pretreatment period
5) Those with substance use disorders (excessive intake of opioids, cannabinoids or other illicit drugs, alcohol or caffeine [as determined by the investigator ], or recreational use of antipsychotic drugs)
6) Women who are breastfeeding or pregnant during the pretreatment period. For women of childbearing potential, a urine pregnancy test will be performed at the beginning of the pretreatment period
7) Women of childbearing potential who meet the following criteria
-Those who did not use a medically appropriate contraceptive method within 4 weeks prior to the start of the pretreatment period
-Those who do not agree to use a medically appropriate contraceptive method during the entire study period and for 4 weeks after discontinuation of the study drug
8) Those with hypersensitivity to lemborexant (LEM) or any of its additives
9) Those with comorbidity or a history of severe hepatic dysfunction
10) Those who are using insomnia medications in excess of the approved dosage
11) Those who used two or more different insomnia medications within one week prior to the start of the pretreatment period
12) Those who took concomitant medications prohibited in this study within 4 weeks (1 week in monotherapy cohort for insomnia medications) prior to the start of the pretreatment period.
13) Those who changed their treatment for mood disorders within 4 weeks prior to the start of the pretreatment period
14) Those who are engaged in shift work involving night shifts
15) Suicidal ideation within 4 weeks prior to the start of the pretreatment period or a suicide attempt within 3 months prior to the start of the pretreatment period
16) Those with severe psychiatric symptoms requiring hospitalization within 4 weeks prior to the start of the pretreatment period
17) Those who have a clinically problematic disease or symptom that is judged by the investigator to have the potential to affect the safety or the evaluation of this study
18) Those who have been administered LEM or have participated in a clinical trial of LEM
19) Those who have been judged by the investigator to be ineligible to participate in this study because of the possibility of affecting safety or any of the study's endpoints

Related Information

• Primary Sponsor: Takaesu Yoshikazu
• Source(s) of Monetary Support: Eisai Co., Ltd.