Crossover Study to Evaluate the Effect of Lemborexant Versus Placebo and Zolpidem on Postural Stability, Auditory Awakening Threshold, and Cognitive Performance in Healthy Subjects 55 Years and Older

NCT ID: NCT03008447

Last Updated: 2019-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-21
• Study Completion Date: 2018-01-03

Brief Summary

E2006-A001-108 is a 4-period crossover study designed to demonstrate that the mean change from baseline in postural stability (worsening) when participants are awakened at approximately 4 hours postdose is significantly less after lemborexant than after zolpidem tartrate extended release following a single-dose administration at bedtime.

Conditions

Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

LEM5; LEM10; PBO; ZOL

Participants will receive LEM5 (one lemborexant \[LEM\] 5 milligram \[mg\] tablet and one zolpidem \[ZOL\]-matched placebo \[PBO\] tablet) in Treatment Period 1. In Treatment Period 2, participants will receive LEM10 (one LEM 10 mg tablet and one ZOL-matched PBO tablet). In Treatment Period 3, participants will receive PBO (one LEM-matched PBO tablet and one ZOL-matched PBO tablet). In Treatment Period 4, participants will receive ZOL (one LEM-matched PBO tablet and one ZOL 6.25 mg tablet).

Group Type: EXPERIMENTAL

LEM5

Intervention Type: DRUG

Single dose of lemborexant 5 mg administered within 5 minutes before bedtime.

LEM10

Intervention Type: DRUG

Single dose of lemborexant 10 mg administered within 5 minutes before bedtime.

ZOL

Intervention Type: DRUG

Single dose of zolpidem 6.25 mg administered within 5 minutes before bedtime.

PBO

Intervention Type: DRUG

Single dose of placebo administered within 5 minutes before bedtime.

LEM10; ZOL; LEM5; PBO

Participants will receive LEM10, ZOL, LEM5, and PBO in Treatments Periods 1, 2, 3, and 4, respectively.

Group Type: EXPERIMENTAL

LEM5

Intervention Type: DRUG

Single dose of lemborexant 5 mg administered within 5 minutes before bedtime.

LEM10

Intervention Type: DRUG

Single dose of lemborexant 10 mg administered within 5 minutes before bedtime.

ZOL

Intervention Type: DRUG

Single dose of zolpidem 6.25 mg administered within 5 minutes before bedtime.

PBO

Intervention Type: DRUG

Single dose of placebo administered within 5 minutes before bedtime.

ZOL; PBO; LEM10; LEM5

Participants will receive ZOL, PBO, LEM10, and LEM5 in Treatment Periods 1, 2, 3, and 4, respectively.

Group Type: EXPERIMENTAL

LEM5

Intervention Type: DRUG

Single dose of lemborexant 5 mg administered within 5 minutes before bedtime.

LEM10

Intervention Type: DRUG

Single dose of lemborexant 10 mg administered within 5 minutes before bedtime.

ZOL

Intervention Type: DRUG

Single dose of zolpidem 6.25 mg administered within 5 minutes before bedtime.

PBO

Intervention Type: DRUG

Single dose of placebo administered within 5 minutes before bedtime.

PBO; LEM5; ZOL; LEM10

Participants will receive PBO, LEM5, ZOL, and LEM10 in Treatment Periods 1, 2, 3, and 4, respectively.

Group Type: EXPERIMENTAL

LEM5

Intervention Type: DRUG

Single dose of lemborexant 5 mg administered within 5 minutes before bedtime.

LEM10

Intervention Type: DRUG

Single dose of lemborexant 10 mg administered within 5 minutes before bedtime.

ZOL

Intervention Type: DRUG

Single dose of zolpidem 6.25 mg administered within 5 minutes before bedtime.

PBO

Intervention Type: DRUG

Single dose of placebo administered within 5 minutes before bedtime.

Interventions

LEM5

Single dose of lemborexant 5 mg administered within 5 minutes before bedtime.

Intervention Type: DRUG

LEM10

Single dose of lemborexant 10 mg administered within 5 minutes before bedtime.

Intervention Type: DRUG

ZOL

Single dose of zolpidem 6.25 mg administered within 5 minutes before bedtime.

Intervention Type: DRUG

PBO

Single dose of placebo administered within 5 minutes before bedtime.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy, non-smoking female participants, aged 55 years and older, or male participants, aged 65 years and older, at the time of informed consent
• Regular sleep timing and duration, per the following criteria:

1. Regular time in bed, between 7 and 9 hours as reported at Screening and verified by the Sleep Diary during the Screening Period before the adaptation night such that time in bed is not less than 7 hours or more than 9 hours on more than 2 of the 7 consecutive nights recorded in the Sleep Diary

2. Regular bedtime, defined as the time the participant attempts to fall asleep, between 22:00 and 01:00 and regular waketime, defined as the time the participant gets out of bed for the day, between 05:00 and 09:00 as reported at Screening and verified by the Sleep Diary during the Screening Period before the adaptation night such that neither bedtime nor waketime is outside of the permitted time windows on more than 2 of the 7 consecutive nights

• Able to detect a 1000 Hertz (Hz) tone at 20 decibels (dB)
• Able to read English at an 8th-grade level

Exclusion Criteria

• Is a female of childbearing potential Note: All females will be considered to be of childbearing potential unless they are postmenopausal (defined as amenorrheic for at least 12 consecutive months, and are postmenopausal without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• A current diagnosis of insomnia disorder, sleep-related breathing disorder, periodic limb movements disorder (PLMD), restless legs syndrome, circadian rhythm sleep disorder, narcolepsy, sleep-related violent behavior, sleep-driving, sleep-eating, or symptoms of another parasomnia that in the investigator's opinion make the participant unsuitable for the study
• Has subjective sleep onset latency (sSOL) > 20 minutes or subjective wake after sleep onset (sWASO) > 60 minutes on more than 2 nights as reported on the Sleep Diary during the Screening Period before the adaptation night
• Latency to persistent sleep (LPS) longer than 30 minutes as measured on the PSG on the Baseline night (or repeat Baseline night, if needed)
• Has a sleep onset Rapid eye movement (REM) period, defined as first epoch of stage REM within 15 minutes of sleep onset, as measured on the PSG on either the adaptation night or Baseline night (or repeat Baseline night, if needed)
• Apnea-Hypopnea Index > 15 or Periodic Limb Movement with Arousal Index > 15 as measured on the PSG on the adaptation night
• Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night
• History of fracture due to a fall within the past 5 years
• Evidence of orthostatic hypotension at Screening
• Use of hearing aid or clinically significant hearing loss
• Presence or history of Meniere's disease, labyrinthitis, benign paroxysmal positional vertigo, no recent vertigo from any other cause, no recent dizziness or head injury
• Unable to stand unaided for a minimum of 2 minutes
• At Screening, fails Romberg test in the clinical judgment of the investigator
• Significant vision loss or inability to read computer screen in <80 lumens per square meter (lux) ambient illumination
• History of drug or alcohol dependency or abuse within approximately the previous 2 years or have a positive urine drug screen at Screening or Baseline
• Self-reports consuming more than 14 alcohol-containing drinks per week (females) or 21 alcohol containing drinks per week (males) at Screening
• A prolonged QT/heart rate corrected QT interval (QTc) (QT interval corrected for Fridericia's formula [QTcF] > 450 milliseconds [ms]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval > 450 ms)
• Any suicidal ideation at Screening or within 6 months of Screening or any lifetime suicidal behavior
• Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, psychiatric or neurological disease, malignancy other than basal cell carcinoma, or chronic pain) or condition that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
• Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half lives, whichever is longer, before the Baseline night
• Scheduled for surgery during the study
• Transmeridian travel across more than 3 time zones in the 2 weeks before the first Baseline night, or plans to travel more than 3 time zones during the study.
• Currently enrolled in another clinical trial or used any investigational drug or device within 28 days or 5 half lives, whichever is longer preceding informed consent
• Hypersensitivity to lemborexant or zolpidem or any of their excipients
• Active viral hepatitis (B or C) as demonstrated by positive serology
• Previous exposure to lemborexant or suvorexant

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Purdue Pharma LP

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NeuroTrials Research, Inc

Atlanta, Georgia, United States

Clinilabs, Inc

New York, New York, United States

Wake Research Assoicates, LLC

Raleigh, North Carolina, United States

Community Research Management Associates d/b/a CTI Clinical Research Center

Cincinnati, Ohio, United States

Countries

United States

References

Gotfried MH, Auerbach SH, Dang-Vu TT, Mishima K, Kumar D, Moline M, Malhotra M. Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials. Drugs Aging. 2024 Sep;41(9):741-752. doi: 10.1007/s40266-024-01135-8. Epub 2024 Aug 9.

Reference Type: DERIVED

PMID: 39120786 (View on PubMed)

Murphy P, Kumar D, Zammit G, Rosenberg R, Moline M. Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening. J Clin Sleep Med. 2020 May 15;16(5):765-773. doi: 10.5664/jcsm.8294. Epub 2020 Feb 6.

Reference Type: DERIVED

PMID: 32022664 (View on PubMed)

Other Identifiers

E2006-A001-108

Identifier Type: -

Identifier Source: org_study_id