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

NCT04742699 | Completed Phase 4

• 1 other identifier: E2006-M081-401
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 9

Brief Summary

This study will be conducted to evaluate whether the approach of direct transitioning to lemborexant (LEM) is supported for insomnia patients who are unsatisfied with current medication. Transition from Following 4 regimens of interest will be investigated; Z-Drug monotherapy, suvorexant (SUV) monotherapy, SUV and benzodiazepine receptor agonists (BZRA) combination therapy, and ramelteon (RMT) and BZRA combination therapy. Patients with insomnia who have been treated with one of the regimens but do not have treatment satisfaction will be enrolled. As a comprehensive indicator of patient satisfaction including treatment efficacy and safety, the proportion of patients with successful transitioning will be evaluated at 2 weeks after transitioning; thus important initial response after transitioning will be evaluated as a primary endpoint. In addition, as a secondary purpose, the treatment continuation, efficacy and tolerability, and the treatment impression for insomnia (Patient Global Impression of Insomnia) for 14 weeks after transitioning will be assessed.

Conditions

Insomnia

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with successful LEM treatment at the end of the first treatment phase to the patients who started the first treatment phase.

  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)

  2 weeks

Secondary Outcomes (4)

• Proportion of patients who continued LEM treatment and those who continued LEM monotherapy at the end of the first treatment phase and the maintenance phase.

  2 - 14 weeks

• Proportion of patients with an itemized positive response on the PGI-I at baseline, the end of the first treatment phase, and the end of the maintenance phase.

  2 - 14 weeks

• Proportion of patients with increased LEM dosage at the end of the first treatment phase and at the end of the maintenance phase.

  2 - 14 weeks

• Occurrence of adverse events during the first treatment phase and the maintenance phase.

  2 - 14 weeks

Study Arms (4)

Z-Drug-mono cohort

EXPERIMENTAL

Patients being treated with Z-drug monotherapy at registration

Drug: Lemborexant (LEM) 5 mg (Z-Drug-mono cohort)

SUV-mono cohort

EXPERIMENTAL

Patients being treated with SUV monotherapy at registration

Drug: Lemborexant (LEM) 5 mg (SUV-mono cohort)

SUV-combination cohort

EXPERIMENTAL

Patients being treated with SUV and BZRA combination therapy at registration

Drug: Lemborexant (LEM) 5 mg (SUV-combination cohort)

RMT-combination cohort

EXPERIMENTAL

Patients being treated with RMT and BZRA combination therapy at registration

Drug: Lemborexant (LEM) 5 mg (RMT-combination cohort)

Interventions

Lemborexant (LEM) 5 mg (Z-Drug-mono cohort) DRUG

1. Pretreatment phase: Continue pre-registration treatment (Z-drug monotherapy) without LEM. 2. First treatment phase: Administer LEM 5 mg/day as a substitute for Z-Drug. Increasing LEM dose to 10 mg/day is allowed. 3. Maintenance phase: Succeed the treatment from the first treatment phase. Changing LEM dose is allowed. Rescue administration of Z-drug or RMT is allowed under a defined condition.

Z-Drug-mono cohort

Lemborexant (LEM) 5 mg (SUV-mono cohort) DRUG

1. Pretreatment phase: Continue pre-registration treatment (SUV monotherapy) without LEM. 2. First treatment phase: Administer LEM 5 mg/day as a substitute for SUV. Increasing to LEM dose to 10 mg/day is allowed. 3. Maintenance phase: Succeed the treatment of the first treatment phase. Changing LEM dose is allowed.

SUV-mono cohort

Lemborexant (LEM) 5 mg (SUV-combination cohort) DRUG

1. Pretreatment phase: Continue pre-registration treatment (SUV and BZRA combination therapy) without LEM. 2. First treatment phase: Administer LEM 5 mg/day as a substitute for SUV and continue BZRA. Increasing to LEM dose to 10 mg/day is allowed. 3. Maintenance phase: Succeed the treatment of the first treatment phase. Changing LEM dose is allowed. Decreasing dose or discontinuation of BZRA is allowed. Rescue administration of Z-drug or RMT is allowed under a defined condition.

SUV-combination cohort

Lemborexant (LEM) 5 mg (RMT-combination cohort) DRUG

1. Pretreatment phase: Continue pre-registration treatment (RMT and BZRA combination therapy) without LEM. 2. First treatment phase: Administer LEM 5 mg/day as a substitute for RMT and continue BZRA. Increasing to LEM dose to 10 mg/day is allowed. 3. Maintenance phase: Succeed the treatment of the first treatment phase. Changing LEM dose is allowed. Decreasing dose or discontinuation of BZRA is allowed. Rescue administration of Z-drug or RMT is allowed under a defined condition.

RMT-combination cohort

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who have voluntarily provided a written informed consent to participate in the study
• Subjects with insomnia aged 20 years or older at the time of informed consent
• 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
• 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.
• 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 in falling asleep, difficulty in 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
• Subjects who can secure at least 7 hours for sleep
• 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
• Subjects who are able to comply with the requirements specified in the study protocol

You may not qualify if:

• 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.
• 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 or an injective 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)
• Subjects with moderate or severe obstructive sleep apnea (OSA).
• 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

Sponsors & Collaborators

• Kurume University: lead
• Eisai Inc.: collaborator
• Mebix Inc: collaborator

Study Sites (9)

YOU ARIYOSHI Sleep Clinic

Kitakyushu, Fukuoka, 802-0084, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

Location

Hirota Clinic

Kurume, Fukuoka, 830-0033, Japan

Location

Kurume University Medical Center

Kurume, Fukuoka, 839-0863, Japan

Location

Kotorii Isahaya Hospital

Isahaya, Nagasaki, 854-0081, Japan

Location

Ohshima Hospital

Nakatsukuma, Saga-ken, 849-0111, Japan

Location

Sleep Support Clinic

Shinagawa, Tokyo, 140-0011, Japan

Location

Sleep & Stress Clinic

Shinagawa, Tokyo, 141-6003, Japan

Location

Kuwamizu Hospital

Kumamoto, 862-0954, Japan

Location

Related Publications (2)

• Ozone M, Hirota S, Ariyoshi Y, Hayashida K, Ikegami A, Habukawa M, Ohshima H, Harada D, Hiejima H, Kotorii N, Murotani K, Nishi Y, Koebis M, Taninaga T, Uchimura N. Self-reported sleep variables, sleep quality, and quality of life assessment in transition to lemborexant in patients with Insomnia: the multicenter, open-label SOMNUS study. Sleep Med X. 2025 Sep 25;10:100149. doi: 10.1016/j.sleepx.2025.100149. eCollection 2025 Dec 15.

  PMID: 41103818 DERIVED

• Ozone M, Hirota S, Ariyoshi Y, Hayashida K, Ikegami A, Habukawa M, Ohshima H, Harada D, Hiejima H, Kotorii N, Murotani K, Taninaga T, Uchimura N. Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter Study. Adv Ther. 2024 Apr;41(4):1728-1745. doi: 10.1007/s12325-024-02811-2. Epub 2024 Mar 9.

  PMID: 38460107 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

lemborexant; leukocyte endogenous mediator

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Study Officials

• Motohiro Ozone

  Kurume University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 8, 2021
• Study Start: March 24, 2021
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2022
• Last Updated: March 15, 2023

Record last verified: 2023-03

Locations

JP (9)