Study to Evaluate the Effect of Lemborexant Versus Placebo on Driving Performance in Healthy Adult and Elderly Subjects

NCT02583451 | Completed Phase 1 FDA Drug

• 1 other identifier: E2006-E044-106
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo- and active-controlled, 4-period crossover study of lemborexant in healthy adult and elderly subjects to evaluate driving performance

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (1)

• Change of standard deviation of lateral position (SDLP) during an on-road driving test

  Day 2, Day 9, Day 23, Day 30, Day 44, Day 51, Day 65, and Day 72

Secondary Outcomes (8)

• Number of lapses on the driving test

  Day 2, Day 9, Day 23, Day 30, Day 44, Day 51, Day 65, and Day 72

• Outliers on SDLP

  Day 2, Day 9, Day 23, Day 30, Day 44, Day 51, Day 65, and Day 72

• Outliers on number of lapses

  Day 2, Day 9, Day 23, Day 30, Day 44, Day 51, Day 65, and Day 72

• Percentage of participants who never started a scheduled driving test or who stopped prematurely

  Day 2, Day 9, Day 23, Day 30, Day 44, Day 51, Day 65, and Day 72

• Standard deviation of lateral position (SDLP) during an on-road driving test, by age group

  Day 2, Day 9, Day 23, Day 30, Day 44, Day 51, Day 65, and Day 72

Study Arms (5)

Treatment A

EXPERIMENTAL

Treatment A is a placebo tablet matching lemborexant and placebo tablet matching zopiclone on nights in the clinic; placebo tablet matching lemborexant on nights at home.

Drug: Placebo tablet matching lemborexant; Drug: Placebo tablet matching zopiclone

Treatment B

EXPERIMENTAL

Treatment B is zopiclone 7.5 mg tablet and placebo tablet matching lemborexant on nights in the clinic; placebo tablet matching lemborexant on nights at home.

Drug: Placebo tablet matching lemborexant; Drug: Zopiclone 7.5 mg

Treatment C

EXPERIMENTAL

Treatment C is lemborexant 2.5 mg tablet and placebo tablet matching zopiclone on nights in the clinic; lemborexant 2.5 mg tablet on nights at home.

Drug: Placebo tablet matching zopiclone; Drug: Lemborexant 2.5 mg

Treatment D

EXPERIMENTAL

Treatment D is lemborexant 5 mg tablet and placebo tablet matching zopiclone on nights in the clinic; lemborexant 5 mg tablet on nights at home.

Drug: Placebo tablet matching zopiclone; Drug: Lemborexant 5 mg

Treatment E

EXPERIMENTAL

Treatment E is lemborexant 10 mg tablet and placebo tablet matching zopiclone on nights in the clinic; lemborexant 10 mg tablet on nights at home.

Drug: Placebo tablet matching zopiclone; Drug: Lemborexant 10 mg

Interventions

Placebo tablet matching lemborexant DRUG

Tablet form taken orally at bedtime.

Treatment A; Treatment B

Placebo tablet matching zopiclone DRUG

Tablet form taken orally at bedtime.

Treatment A; Treatment C; Treatment D; Treatment E

Zopiclone 7.5 mg DRUG

7.5 mg tablet taken orally at bedtime.

Treatment B

Lemborexant 2.5 mg DRUG

2.5 tablet taken orally at bedtime.

Treatment C

Lemborexant 5 mg DRUG

5 mg tablet taken orally at bedtime.

Treatment D

Lemborexant 10 mg DRUG

10 mg tablet taken orally at bedtime.

Treatment E

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, male or female, aged 21 years or older at Screening
• Regular time spent in bed between 7.0 and 8.5 hours per night
• Regular bedtime, defined as the time the participant attempts to fall asleep, between 22:00 hours and 01:00 hours, and regular waketime, defined as the time the participant gets out of bed for the day, between 05:00 hours and 09:00 hours
• Body mass index (BMI) ≥18 and \<31 kg/m2 at Screening
• Subjective sleep onset latency (sSOL) \<30 minutes and subjective wake after sleep onset (sWASO) \<60 minutes on the Sleep Diary
• At least 3 years of experience driving at least 3000 km per year
• Holds a valid license to drive a vehicle in the European Union (EU) as confirmed at the Screening visit
• Has driving ability during the practice driving test that is judged to be adequate by the driving instructor
• Able to communicate adequately (written and verbal) in either Dutch or English as determined by the investigator

You may not qualify if:

• Habitually naps more than 3 times per week
• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[B-hCG\] test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG). 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.
• Females of childbearing potential who:
• Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation.
• Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from sexually active during the study period or for 28 days after study drug discontinuation.
• Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or 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 \[ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing\]).
• Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 28 days after study drug discontinuation.
• Clinically significant illness that requires medical treatment between Screening and Baseline
• Any clinically abnormal symptom or organ impairment found by medical history at Screening or Baseline and physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment
• Has a QT interval corrected using Fridericia's formula interval (QTcF interval) \>450 ms demonstrated on repeated ECGs (repeated only if initial ECG showed corrected QT interval (QTc) \>450 ms) at Screening or Baseline
• Has a history of or a family history of congenital QT prolongation or with a history of risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome), or uses concomitant medications that prolong the QT/QT interval corrected for heart rate (QTc interval)
• Has systolic blood pressure (BP) \>140 mmHg (age 21-59) or \>150 mmHg (age ≥60) or diastolic BP \>90 mmHg (all ages) at Screening or Baseline
• Has a resting heart rate \<50 or ≥100 beats/min at Screening or Baseline
• Has a history of drug or alcohol dependency or abuse (as defined by DSM-5 criteria) within approximately 2 years before Screening
• Any suicidal ideation with intent with or without a plan within 6 months of the Screening Period (ie, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS)

Sponsors & Collaborators

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

Study Sites (1)

Maastricht University

Maastricht, 6229 GS, Netherlands

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

• Vermeeren A, Jongen S, Murphy P, Moline M, Filippov G, Pinner K, Perdomo C, Landry I, Majid O, Van Oers ACM, Van Leeuwen CJ, Ramaekers JG, Vuurman EFPM. On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers. Sleep. 2019 Apr 1;42(4):zsy260. doi: 10.1093/sleep/zsy260.

  PMID: 30597112 DERIVED

MeSH Terms

Interventions

zopiclone; lemborexant

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 22, 2015
• Study Start: November 1, 2015
• Primary Completion: January 31, 2017
• Study Completion: February 1, 2017
• Last Updated: September 6, 2018

Record last verified: 2017-11

Locations

NL (1)