A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia

• ClinicalTrials.gov Identifier: NCT04009577
• Recruitment Status: Completed
• First Posted: July 5, 2019
• Last Update Posted: November 19, 2020
• Sponsor: Eisai Inc.
• Information provided by (Responsible Party): Eisai Inc.

Study Description

Brief Summary:

The primary objective of the study is to evaluate the proportion of adult [greater than or equal to (>=) 18 years] participants with insomnia disorder taking zolpidem tartrate immediate release (ZOL-IR) or zolpidem tartrate extended release (ZOL-ER), intermittently or frequently, who transition to lemborexant 5 milligram (mg) (LEM5) or 10 mg (LEM10) after 2 weeks of receiving LEM.

Condition or disease	Intervention/treatment	Phase
Insomnia	Drug: LEM 5 mg; Drug: LEM 10 mg	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Pilot Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant for the Treatment of Insomnia
• Actual Study Start Date: July 15, 2019
• Actual Primary Completion Date: March 17, 2020
• Actual Study Completion Date: June 26, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1 (LEM 5 mg); Participants who were taking zolpidem tartrate (ZOL) at least 3 but fewer than 5 nights per week, for each of at least 2 weeks of the 3-week Screening Period, will initially receive LEM 5 mg administered as a tablet, orally for up to 2 weeks. Participants who meet both criteria for intermittent (Cohort 1) and frequent ZOL use (Cohort 2A and 2B) for 1 week each of the last 2 weeks of the 3-week Screening Period will be assigned to Cohort 1 and also will receive LEM 5mg.	Drug: LEM 5 mg; LEM tablet.; Other Names: E2006; Lemborexant
Experimental: Cohort 2A (LEM 5 mg); Participants who were taking ZOL at least 5 nights per week, during, at minimum, the last 2 weeks of the 3-week Screening Period, will initially receive LEM 5 mg administered as a tablet, orally for up to 2 weeks.	Drug: LEM 5 mg; LEM tablet.; Other Names: E2006; Lemborexant
Experimental: Cohort 2B (LEM 10 mg); Participants who were taking ZOL at least 5 nights per week, during, at minimum, the last 2 weeks of the 3-week Screening Period, will initially receive LEM 10 mg administered as a tablet, orally for up to 2 weeks.	Drug: LEM 10 mg; LEM tablet.; Other Names: E2006; Lemborexant

Outcome Measures

Primary Outcome Measures :

1. Percentage of Overall Participants who Transition to LEM at the end of the Titration Period [ Time Frame: Up to 2 Weeks ]
   Transition to LEM is defined as a participant who remains on LEM at the end of the 2-week titration period and either 1) enters the extension phase, or 2) chooses to not enter the extension phase for reasons not related to LEM (including, but not limited to, time commitment related to the study, study-related travel expenses or preference to continue insomnia management with another health care provider).

Secondary Outcome Measures :

1. Percentage of Participants who Transition to LEM at the End of the 2-Week Titration Period within Each Cohort [ Time Frame: Up to 2 Weeks ]
2. Percentage of Participants in the LEM5 Treatment Groups with Dose Increasing to LEM10 at the End of the Titration Period by Cohort and Overall [ Time Frame: Up to 2 Weeks ]
3. Percentage of Participants in LEM10 Treatment Group with Dose Decreasing to LEM5 at the End of the Titration Period in Cohort 2 [ Time Frame: Up to 2 Weeks ]
4. Percentage of Participants with Positive Medication Effect Rating on Each Patient Global Impression of Insomnia (PGI-I) Item at the End of the 2-Week Titration Period by Cohort and Overall Using End of the Titration Period Treatment [ Time Frame: Up to 2 Weeks ]
   The PGI-I is a self-report assessment of participant perception of the effects of a medication on their sleep. The PGI-I has 3 items related to study medication effects (a) helped/worsened sleep, (b) decreased/increased time to fall asleep, (c) increased/decreased total sleep time, and 1 item related to perceived appropriateness of study medication strength. The first 3 items are answered on a 3-point scale (1=positive medication effect, 2=neutral medication effect, 3=negative medication effect) and the last item on a different 3 point scale (medication: 1=too strong, 2=just right, 3=too weak). The PGI-I will be completed each morning following a dose of ZOL or LEM taken the prior evening during the screening and titration periods.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5) criteria for Insomnia Disorder, either currently or prior to zolpidem use, as follows:

   • Complains of dissatisfaction with nighttime sleep, in the form of difficulty staying asleep and/or awakening earlier in the morning than desired despite adequate opportunity for sleep
   • Frequency of complaint >=3 times per week
   • Duration of complaint >=3 months
   • Associated with complaint of daytime impairment
2. Reports spending at least 7 hours in bed per night
3. History of intermittent [taking zolpidem at least 3 or 4 nights per week], or frequent use (at least 5 nights per week) of ZOL-IR or ZOL-ER, for at least 1 month
4. Confirmation of intermittent or frequent use of zolpidem (based on review of drug use data). Intermittent use is defined as taking zolpidem at least 3 but fewer than 5 nights per week, for at least 2 weeks each of the 3-week Screening Period. Frequent use is defined as taking zolpidem at least 5 nights per week, during, at minimum, the last 2 weeks of the 3-week Screening Period
5. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
6. Willing not to start another pharmacologic treatment for the management of insomnia during the participant's participation in the study

Exclusion Criteria:

1. Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive serum pregnancy test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug

2. Females of childbearing potential who:

   Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

   • total abstinence (if it is their preferred and usual lifestyle)
   • an intrauterine device or intrauterine hormone-releasing system (IUS)
   • a contraceptive implant
   • an oral contraceptive (Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation)
   • have a vasectomized partner with confirmed azoospermia
   • Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
3. Any history of moderate or severe obstructive sleep apnea (OSA)
4. Current evidence of a clinically significant, active respiratory disorder other than mild OSA. This includes bronchiectasis, emphysema, asthma, chronic obstructive pulmonary disease or any other pulmonary disorder identified by review of medical history or physical examination, and which in the opinion of the investigator, could compromise the participant's safety or interfere with study assessments

5. A current diagnosis of periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows:

   • STOP-Bang score >=5 (participants previously diagnosed with mild OSA are not excluded)
   • International Restless Legs Scale (IRLS) score >=16
6. Habitually naps during the day more than 3 times per week
7. Reports symptoms potentially related to narcolepsy, that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy
8. Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior (eg, making phone calls or preparing and eating food while sleeping), whether spontaneous or associated with a pharmacological sleep agent
9. Takes a dose of ZOL-IR greater (>)10 mg per night, or ZOL-ER >12.5 mg per night
10. Takes a dose of zolpidem that is lower than what is prescribed
11. Reports having altered zolpidem tablets
12. Unwilling to forgo alcohol consumption within 3 hours of bedtime for the duration of participation in the study
13. Used any prohibited prescription or over-the-counter concomitant medications within 1-week or 5 half-lives, whichever is longer, before the first dose of study medication (A list of prohibited concomitant medications is presented in the protocol)
14. Used any pharmacologic modality of treatment for insomnia other than zolpidem, including marijuana, within 1-week or 5 half-lives, whichever is longer, before the Screening Period
15. A prolonged difference between QTc corrected by Fridericia's formulas (QTcF) interval [QTcF >450 millisecond (ms)] as demonstrated by a repeated electrocardiogram
16. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (ie, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale [C-SSRS])
17. Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS)
18. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, and renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded
19. Hypersensitivity to LEM or any of the excipients
20. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study
21. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery, which requires only local anesthesia and which can be undertaken as a day case without inpatient stay postoperatively, need not result in exclusion if in the opinion of the investigator this operation does not interfere with the study procedures and patient safety
22. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years
23. History of drug or alcohol dependency or abuse within approximately the last 2 years
24. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5 times the half-life, whichever is longer, preceding informed consent
25. Previously participated in any clinical trial of LEM

Contacts and Locations

Locations

United States, Arizona

PACT

Glendale, Arizona, United States, 85306

United States, California

Northern California Research Corp

Sacramento, California, United States, 95821

Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS

San Diego, California, United States, 92103

SDS Clinical Trials, Inc.

Santa Ana, California, United States, 92705

United States, Florida

Fleming Island Center For Clinical Research - ERN-PPDS

Fleming Island, Florida, United States, 32003

MD Clinical

Hallandale Beach, Florida, United States, 33009

Clinical Neuroscience Solutions Inc

Jacksonville, Florida, United States, 32256

Clinical Neuroscience Solutions Inc

Orlando, Florida, United States, 32801

United States, Georgia

NeuroTrials Research Inc. - BTC - PPDS

Atlanta, Georgia, United States, 30342

SleepCare Research Institute Inc

Stockbridge, Georgia, United States, 30281

United States, Illinois

Chicago Research Center Inc - ClinEdge - PPDS

Chicago, Illinois, United States, 60634

United States, Maryland

Centennial Medical Group - Elkridge - Rx Trials

Elkridge, Maryland, United States, 21075

United States, New Mexico

Albuquerque Neurosciences Inc

Albuquerque, New Mexico, United States, 87109

United States, New York

Clinilabs Drug Development Corporation

New York, New York, United States, 10019

United States, Ohio

CTI Clinical Research Center - ClinEdge - PPDS

Cincinnati, Ohio, United States, 45212

United States, Tennessee

Clinical Neuroscience Solutions Inc

Memphis, Tennessee, United States, 38119

United States, Texas

FutureSearch Trials of Neurology

Austin, Texas, United States, 78731

Sponsors and Collaborators

Eisai Inc.

More Information

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT04009577
• Other Study ID Numbers: E2006-A001-312
• First Posted: July 5, 2019
• Last Update Posted: November 19, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website https://eisaiclinicaltrials.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:

Insomnia; Sleep Initiation and Maintenance Disorders; Insomnia Disorder; Sleeplessness; E2006; Zolpidem; Lemborexant

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders