An Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Transitioning to Lemborexant in Japanese Subjects With Insomnia

JRCT ID: jRCTs071200093

Registered date:28/01/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: insomnia
• Date of first enrollment: 24/03/2021
• Target sample size: 120
• Study type: Interventional

Intervention(s)

LEM is orally administered once daily immediately before going to bed.
LEM administration is to be performed during the first treatment phase and maintenance phases according to the following rules;
1. Pretreatment phase: not administered.
2. First treatment phase:
- Prescribe LEM 5 mg / day at baseline and start administration.
- Maintaining LEM 5 mg / day for 7 days is recommended, but increasing the dose to LEM 10 mg / day is allowed in case of insufficient efficacy, after consulting at the study site.
3. Maintenance phase:
- Changing the dose of LEM in consultation with the patient is allowed.

Outcome(s)

Primary Outcome

The primary endpoint is the proportion of patients with successful LEM treatment at the end of the first treatment phase to the patients who started the first treatment phase. Evaluation is performed for each treatment group.
Successful LEM treatment at the end of the first treatment phase is primarily defined as follows;
- Patients who wish to continue LEM treatment at the end of the first treatment phase and actually move on to the maintenance phase
- Patients who wish to continue LEM treatment at the end of the first treatment phase but do not move to the maintenance phase with a reason not related to the efficacy or safety of LEM treatment (e.g., relocation, clinic transfer, or a burden of site visit expenses)

Secondary Outcome

1) Proportion of patients who continued LEM treatment and those who continued LEM monotherapy at the end of the first treatment phase and at the end of the maintenance phase.
2) Proportion of patients whose PGI-I by item responded positively at baseline, at the end of the first treatment phase, and at end of the maintenance phase.
3) Proportion of patients with increased LEM dosage at the end of the first treatment phase and at the end of the maintenance phase.
4) Occurrence of adverse events during the first treatment phase and the maintenance phase.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Subjects who have voluntarily provided a written informed consent to participate in the study
2) Subjects with insomnia aged 20 years or older at the time of informed consent
3) Subjects who are dissatisfied with the efficacy or tolerability of prior medications and wish to transition from them.
For example;
- Subjects who are treated with Z-Drug monotherapy or a combination of BZRA and RMT, and have particularly difficulties with sleep maintenance
-Subjects who are treated with SUV monotherapy or a combination of BZRA and SUV, and have particularly difficulties with sleep onset
- Subjects who are treated with a combination therapy of BZRA and SUV or BZRA and RMT, and wish to reduce or discontinue BZRA
4) Subjects with frequent use (i.e. at least 5 nights a week) of Z-drug monotherapy, SUV monotherapy, combination therapy with BZRA and SUV, or combination therapy with BZRA and RMT in the month before the start of the pretreatment phase.
5) Subjects who meet the criteria for insomnia disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as follows
- Despite an adequate opportunity for sleep, subjects have night sleep-related complaints accompanied by at least 1 of the following symptoms: difficulty falling asleep, difficulty staying asleep, and waking up early
- The difficulty in sleeping occurs at least 3 nights a week
- The difficulty in sleeping persists for at least 3 months
- The difficulty in sleeping causes daytime dysfunction
6) Subjects who can secure at least 7 hours for sleep
7) Subjects who have a documented use of a prior medication(s) for the treatment of insomnia at least 5 nights in the last 2 weeks of the pretreatment phase
8) Subjects who are able to comply with the requirements specified in the study protocol

Exclude criteria

1) Female who are breastfeeding or pregnant at pretreatment phase. If pregnancy cannot be completely denied by interview, a serum beta-hCG test will be performed.
2) Females of childbearing potential who did not use a highly effective method of contraception, which includes:
-total abstinence (if it is their preferred and usual lifestyle)
-use of condom
-an intrauterine device (IUD)
-a contraceptive implant
-an oral contraceptive
-have a vasectomized partner with confirmed azoospermia
The following methods are not considered as contraception: periodic abstinence such as calendar method, ovulation method, symptothermal method, basal body temperature method, and withdrawal method)
Do not agree to use a highly effective method of contraception (as described above)
3) Subjects with moderate or severe obstructive sleep apnea (OSA).
4) Subjects with any symptoms and/or disease that may affect the safety or the endpoints of the study in the opinion of the investigator (see the examples below)
- Cardiac disorder [including subjects with repeated QT interval prolongation*1 in previous ECG tests. For subjects whose QT interval abnormality cannot be ruled out by interview, ECG tests should be performed by baseline (Visit 2) to confirm the normality of corrected QT (QTc) interval].
*1: QT interval corrected by Fridericia's formulas (QTcF) exceeds 450 ms
- Respiratory disorder other than mild OSA
- Digestive disease
- Kidney disease [including renal dysfunction]
- Neurological disorders [including intellectual incapacity or cognitive decline with disorientation to the person, place, time or situation]
- Mental disorders
- Chronic pain [pain disorders]
- Carcinoma within 5 years [excluding appropriately treated basal cell carcinoma]
5) Currently has certain sleep disorders other than insomnia such as periodic limb movement disorder, restless legs syndrome, and circadian rhythm sleep disorder. Subjects diagnosed with mild OSA are not excluded from the study
6) Currently has a habit of napping for a long period of time 3 or more times a week in the opinion of the investigator.
7) Currently has narcolepsy or cataplexy
8) Subjects who are using a prior medication(s) for the treatment of insomnia at doses exceeding the dosage and administration approved in Japan
9) Subjects who are using two or more BZRAs
10) Subjects who are using sedative medication(s),
11) Have used prohibited concomitant drugs within 1 week before the start of the pretreatment phase
12) Have newly started nonpharmacologic treatments for insomnia (eg, cognitive behavioral therapy) within 1 week before the pretreatment phase
13) Cannot refrain from excessive alcohol consumption during study participation
14) History of hypersensitivity to any of the excipients of LEM
15) Subjects with moderate or severe hepatic impairment (subjects whose AST, ALT, or gamma-GTP is 3 times or more the upper limit of the institutional reference interval)
16) History of antipsychotic drugs use within the past 2 years or attempted suicide, which may affect the safety or the endpoints of the study in the opinion of the investigator
17) Subjects who have previously taken LEM (including subjects who have participated in a clinical trial of LEM)
18) Subjects deemed inappropriate to participate in this study in the opinion of the investigator

Related Information

• Primary Sponsor: Ozone Motohiro
• Secondary Sponsor: Eisai Co., Ltd.