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

NCT03008447 | Completed Phase 1 FDA Drug

• 1 other identifier: E2006-A001-108
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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

Keywords

E2006; postural stability; auditory awakening threshold; cognitive performance; healthy participants

Outcome Measures

Primary Outcomes (1)

• Change from time-matched baseline in postural stability for LEM5 and LEM10 compared to zolpidem (ZOL) at approximately 4 hours postdose

  Magnitude of body sway upon being awakened at approximately 4 hours after receiving lemborexant 5 milligrams (mg) (LEM5), lemborexant 10 mg (LEM10), zolpidem 6.25 mg, or placebo.

  approximately 4 hours postdose at each of 4 single-dose treatment periods (up to 43 days)

Secondary Outcomes (12)

• Change from time-matched baseline in postural stability for LEM5 and LEM10 compared to ZOL and placebo (PBO) at approximately 8 hours postdose

  approximately 4 hours postdose at each of 4 single-dose treatment periods (up to 43 days)

• Change from time-matched baseline in postural stability for LEM5 and LEM10 compared to PBO at approximately 4 hours postdose

  approximately 4 hours postdose at each of 4 single-dose treatment periods (up to 43 days)

• Change from time-matched baseline in auditory awakening threshold (AAT) for LEM5 and LEM10 compared to ZOL and PBO at approximately 4 hours postdose

  approximately 4 hours postdose at each of 4 single-dose treatment periods (up to 43 days)

• Change from time-matched baseline on summary variables from power of attention for LEM5 and LEM10 compared to ZOL and PBO at approximately 4 hours postdose

  approximately 4 hours postdose at each of 4 single-dose treatment periods (up to 43 days)

• Change from time-matched baseline on summary variables from power of attention for LEM5 and LEM10 compared to ZOL and PBO at approximately 8 hours postdose

  approximately 4 hours postdose at each of 4 single-dose treatment periods (up to 43 days)

Study Arms (4)

LEM5; LEM10; PBO; ZOL

EXPERIMENTAL

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).

Drug: LEM5; Drug: LEM10; Drug: ZOL; Drug: PBO

LEM10; ZOL; LEM5; PBO

EXPERIMENTAL

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

Drug: LEM5; Drug: LEM10; Drug: ZOL; Drug: PBO

ZOL; PBO; LEM10; LEM5

EXPERIMENTAL

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

Drug: LEM5; Drug: LEM10; Drug: ZOL; Drug: PBO

PBO; LEM5; ZOL; LEM10

EXPERIMENTAL

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

Drug: LEM5; Drug: LEM10; Drug: ZOL; Drug: PBO

Interventions

LEM5 DRUG

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

LEM10; ZOL; LEM5; PBO; LEM5; LEM10; PBO; ZOL; PBO; LEM5; ZOL; LEM10; ZOL; PBO; LEM10; LEM5

LEM10 DRUG

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

LEM10; ZOL; LEM5; PBO; LEM5; LEM10; PBO; ZOL; PBO; LEM5; ZOL; LEM10; ZOL; PBO; LEM10; LEM5

ZOL DRUG

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

LEM10; ZOL; LEM5; PBO; LEM5; LEM10; PBO; ZOL; PBO; LEM5; ZOL; LEM10; ZOL; PBO; LEM10; LEM5

PBO DRUG

Single dose of placebo administered within 5 minutes before bedtime.

LEM10; ZOL; LEM5; PBO; LEM5; LEM10; PBO; ZOL; PBO; LEM5; ZOL; LEM10; ZOL; PBO; LEM10; LEM5

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead
• Purdue Pharma LP: collaborator

Study Sites (4)

NeuroTrials Research, Inc

Atlanta, Georgia, 30342, United States

Location

Clinilabs, Inc

New York, New York, 10019, United States

Location

Wake Research Assoicates, LLC

Raleigh, North Carolina, 27612, United States

Location

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

Cincinnati, Ohio, 45212, United States

Location

Related Publications (2)

• 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.

  PMID: 39120786 DERIVED

• 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.

  PMID: 32022664 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2016
• First Posted: January 2, 2017
• Study Start: November 21, 2016
• Primary Completion: January 3, 2018
• Study Completion: January 3, 2018
• Last Updated: August 1, 2019

Record last verified: 2017-11

Locations

US (4)