A Study to Determine the Abuse Potential of Single Oral Doses of Lemborexant Compared to Zolpidem, Suvorexant and Placebo in Healthy, Non-Dependent, Recreational Sedative Users

NCT03158025 | Completed Phase 1 FDA Drug

• 1 other identifier: E2006-A001-103
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the abuse potential of lemborexant (E2006) in comparison to placebo and 2 controls with known abuse potential (ie, zolpidem and suvorexant) with similar indications (zolpidem and suvorexant) or mechanisms of action (suvorexant).

Conditions

Insomnia Disorders

Keywords

Recreational sedatives; Healthy participants; Lemborexant; E2006; Zolpidem; Suvorexant

Outcome Measures

Primary Outcomes (1)

• Mean peak Maximum Effect (Emax) score for Drug Liking on a Visual Analog Scale (VAS)

  Analysis is conducted to evaluate abuse potential. Participants will be asked to respond to the following question on a VAS: "At this moment, my liking for this drug is." The VAS will be scored as an integer from 0 (strong disliking) to 100 (strong liking). The neutral point equals 50 and will be labeled with the anchor "neither like nor dislike."

  0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 (all Day 1), and 24 hours (Day 2) post-dose of each treatment cycle (up to 11 weeks)

Secondary Outcomes (40)

• Mean time to peak effect (TEmax) score for Drug Liking on a VAS

  0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 (all Day 1), and 24 hours (Day 2) post-dose of each treatment cycle (up to 11 weeks)

• Mean peak minimum effect (Emin) score for Drug Liking on a VAS

  0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 (all Day 1), and 24 hours (Day 2) post-dose of each treatment cycle (up to 11 weeks)

• Mean time to peak minimum effect (TEmin) score for Drug Liking on a VAS

  0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 (all Day 1), and 24 hours (Day 2) post-dose of each treatment cycle (up to 11 weeks)

• Mean time-averaged area under the effects curve (TA_AUE) score for Drug Liking on a VAS

  0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 (all Day 1), and 24 hours (Day 2) post-dose of each treatment cycle (up to 11 weeks)

• Mean Emax score for Overall Drug Liking (Overall, my liking for this drug is) on a VAS

  12 (Day 1), 24 (Day 2), and 48 hours (Day 3) post-dose of each treatment cycle (up to 11 weeks)

Study Arms (6)

Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg

EXPERIMENTAL

Participants will receive the following treatments (orally) in Treatments Periods 1 through 6, respectively: Placebo (3 × placebo lemborexant \[LEM\] tablets; 3 × placebo zolpidem \[ZOL\] tablets; 2 × placebo suvorexant \[SUV\], over-encapsulated); LEM 10 milligrams (mg) (1 × 10 mg LEM tablet; 2 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); SUV 40 mg (2 × 20 mg SUV tablets, over-encapsulated; 3 × placebo ZOL tablets; 3 × placebo LEM tablets); LEM 20 mg (2 × 10 mg LEM tablets; 1 × placebo LEM tablet; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); ZOL 30 mg (3 × 10 mg ZOL tablets; 3 × placebo LEM tablets; 2 × placebo SUV, over-encapsulated); LEM 30 mg (3 × 10 mg LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated). Each treatment period will be separated by a washout interval of at least 14 days.

Drug: Zolpidem tablets; Drug: Suvorexant tablets, over-encapsulated; Drug: Lemborexant tablets; Drug: Placebo lemborexant; Drug: Placebo zolpidem; Drug: Placebo suvorexant

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg

EXPERIMENTAL

Participants will receive the following treatments (orally) in Treatments Periods 1 through 6, respectively: LEM 10 mg (1 × 10 mg LEM tablet; 2 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 20 mg (2 × 10 mg LEM tablets; 1 × placebo LEM tablet; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); placebo (3 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 30 mg (3 × 10 mg LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); SUV 40 mg (2 × 20 mg SUV tablets, over-encapsulated; 3 × placebo ZOL tablets; 3 × placebo LEM tablets); ZOL 30 mg (3 × 10 mg ZOL tablets; 3 × placebo LEM tablets; 2 × placebo SUV, over-encapsulated). Each treatment period will be separated by a washout interval of at least 14 days.

Drug: Zolpidem tablets; Drug: Suvorexant tablets, over-encapsulated; Drug: Lemborexant tablets; Drug: Placebo lemborexant; Drug: Placebo zolpidem; Drug: Placebo suvorexant

LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg

EXPERIMENTAL

Participants will receive the following treatments (orally) in Treatments Periods 1 through 6, respectively: LEM 20 mg (2 × 10 mg LEM tablets; 1 × placebo LEM tablet; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 30 mg (3 × 10 mg LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 10 mg (1 × 10 mg LEM tablet; 2 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); ZOL 30 mg (3 × 10 mg ZOL tablets; 3 × placebo LEM tablets; 2 × placebo SUV, over-encapsulated); placebo (3 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); SUV 40 mg (2 × 20 mg SUV tablets, over-encapsulated; 3 × placebo ZOL tablets; 3 × placebo LEM tablets). Each treatment period will be separated by a washout interval of at least 14 days.

Drug: Zolpidem tablets; Drug: Suvorexant tablets, over-encapsulated; Drug: Lemborexant tablets; Drug: Placebo lemborexant; Drug: Placebo zolpidem; Drug: Placebo suvorexant

LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo

EXPERIMENTAL

Participants will receive the following treatments (orally) in Treatments Periods 1 through 6, respectively: LEM 30 mg (3 × 10 mg LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); ZOL 30 mg (3 × 10 mg ZOL tablets; 3 × placebo LEM tablets; 2 × placebo SUV, over-encapsulated); LEM 20 mg (2 × 10 mg LEM tablets; 1 × placebo LEM tablet; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); SUV 40 mg (2 × 20 mg SUV tablets, over-encapsulated; 3 × placebo ZOL tablets; 3 × placebo LEM tablets); LEM 10 mg (1 × 10 mg LEM tablet; 2 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); placebo (3 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated). Each treatment period will be separated by a washout interval of at least 14 days.

Drug: Zolpidem tablets; Drug: Suvorexant tablets, over-encapsulated; Drug: Lemborexant tablets; Drug: Placebo lemborexant; Drug: Placebo zolpidem; Drug: Placebo suvorexant

ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

EXPERIMENTAL

Participants will receive the following treatments (orally) in Treatments Periods 1 through 6, respectively: ZOL 30 mg (3 × 10 mg ZOL tablets; 3 × placebo LEM tablets; 2 × placebo SUV, over-encapsulated); SUV 40 mg (2 × 20 mg SUV tablets, over-encapsulated; 3 × placebo ZOL tablets; 3 × placebo LEM tablets); LEM 30 mg (3 × 10 mg LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); placebo (3 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 20 mg (2 × 10 mg LEM tablets; 1 × placebo LEM tablet; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 10 mg (1 × 10 mg LEM tablet; 2 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated). Each treatment period will be separated by a washout interval of at least 14 days.

Drug: Zolpidem tablets; Drug: Suvorexant tablets, over-encapsulated; Drug: Lemborexant tablets; Drug: Placebo lemborexant; Drug: Placebo zolpidem; Drug: Placebo suvorexant

SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg

EXPERIMENTAL

Participants will receive the following treatments (orally) in Treatments Periods 1 through 6, respectively: SUV 40 mg (2 × 20 mg SUV tablets, over-encapsulated; 3 × placebo ZOL tablets; 3 × placebo LEM tablets); placebo (3 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); ZOL 30 mg (3 × 10 mg ZOL tablets; 3 × placebo LEM tablets; 2 × placebo SUV, over-encapsulated); LEM 10 mg (1 × 10 mg LEM tablet; 2 × placebo LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 30 mg (3 × 10 mg LEM tablets; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated); LEM 20 mg (2 × 10 mg LEM tablets; 1 × placebo LEM tablet; 3 × placebo ZOL tablets; 2 × placebo SUV, over-encapsulated). Each treatment period will be separated by a washout interval of at least 14 days.

Drug: Zolpidem tablets; Drug: Suvorexant tablets, over-encapsulated; Drug: Lemborexant tablets; Drug: Placebo lemborexant; Drug: Placebo zolpidem; Drug: Placebo suvorexant

Interventions

Zolpidem tablets DRUG

Zolpidem 3 x 10 mg tablets will be administered orally.

Also known as: AMBIEN, zolpidem tartrate

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg; LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg; LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo; Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg; SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg; ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

Suvorexant tablets, over-encapsulated DRUG

Suvorexant 2 x 20 mg tablets, over-encapsulated, will be administered orally.

Also known as: BELSOMRA

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg; LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg; LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo; Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg; SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg; ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

Lemborexant tablets DRUG

Lemborexant 1 x 10 mg, 2 x 10 mg, or 3 x 10 mg tablets will be administered orally.

Also known as: E2006

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg; LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg; LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo; Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg; SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg; ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

Placebo lemborexant DRUG

Placebo 1 x 10 mg, 2 x 10 mg, or 3 x 10 mg lemborexant tablets will be administered orally.

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg; LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg; LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo; Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg; SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg; ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

Placebo zolpidem DRUG

Placebo 3 x 10 mg zolpidem tablets will be administered orally.

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg; LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg; LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo; Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg; SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg; ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

Placebo suvorexant DRUG

Placebo 2 x 20 mg suvorexant tablets, over-encapsulated, will be administered orally.

LEM 10 mg, LEM 20 mg, Placebo, LEM 30 mg, SUV 40 mg, ZOL 30 mg; LEM 20 mg, LEM 30 mg, LEM 10 mg, ZOL 30 mg, Placebo, SUV 40 mg; LEM 30 mg, ZOL 30 mg, LEM 20 mg, SUV 40 mg, LEM 10 mg, Placebo; Placebo, LEM 10 mg, SUV 40 mg, LEM 20 mg, ZOL 30 mg, LEM 30 mg; SUV 40 mg, Placebo, ZOL 30 mg, LEM 10 mg, LEM 30 mg, LEM 20 mg; ZOL 30 mg, SUV 40 mg, LEM 30 mg, Placebo, LEM 20 mg, LEM 10 mg

Eligibility Criteria

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

You may qualify if:

• Healthy, male or female, 18 to 55 years of age, inclusive, at the time of informed consent
• Current sedative users who have used sedatives (e.g., zolpidem, benzodiazepines) for recreational (non-therapeutic) purposes (i.e., for psychoactive effects) at least five times in the past year and used sedatives for recreational (non-therapeutic) purposes (i.e., for psychoactive effects) at least once in the 12 weeks before Screening.
• A body mass index (BMI) of 18.0 to 33.0 kilograms per meters squared (kg/m\^2), inclusive, and a minimum weight of 50.0 kg at Screening
• Female participants of childbearing potential with male sexual partners must be using and willing to continue using highly effective contraception for at least 1 month prior to Screening and for at least 1 month after the last study drug administration
• Female participants of non-childbearing potential must meet specified criteria.
• Male participants with female sexual partners of childbearing potential must be using and willing to continue using highly effective contraception from Screening and for at least 1 month after the last study drug administration.
• Participants who are using hormonal contraceptives must be on a stable dose of the same hormonal contraceptive product for at least 1 month before dosing and agree to use the same contraceptive during the study and for at least 1 month after the last study drug discontinuation
• Demonstrate the following in the Qualification Period:
• Ability to distinguish orally administered zolpidem 30 mg and suvorexant 40 mg from placebo on the bipolar Drug Liking (at this moment) Visual analog scale (VAS), defined as a ≥15 point peak increase for Drug Liking in response to zolpidem and suvorexant relative to placebo following drug administration. A peak score of ≥65 must be indicated on the bipolar measure of Drug Liking (at this moment) in response to zolpidem and suvorexant
• Display an acceptable placebo response, defined as a VAS response between 40 to 60 inclusive, for peak (Emax) Drug Liking (at this moment)
• Demonstrate responses to zolpidem and suvorexant that are consistent with discrimination relative to placebo on other subjective measures, as judged by the study center staff
• Tolerate study treatment (eg, no episodes of vomiting within the first 3 hours postdose) and demonstrate ability to complete the pharmacodynamic assessments (eg, no unarousable sedation within 4 hours postdose)
• Demonstrate general behavior suggestive that the participant could successfully complete the study, as judged by the study center staff.
• Able to speak, read, and understand English sufficiently to allow completion of all study assessments
• Must provide written informed consent prior to the initiation of any protocol-specific procedures

You may not qualify if:

• Substance or alcohol dependence (excluding nicotine and caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Text Revision (DSM IV-TR), and/or have ever been in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence
• Female participants who are currently pregnant (have a positive pregnancy test) or lactating or who are planning to become pregnant within 1 month of the last study drug administration. No ovum donation is allowed during the study period and for 1 month after study drug discontinuation.
• Are currently abstinent and do not agree to use a highly effective form of contraception or refrain from sexual activity during the study period and for 1 month after study drug discontinuation
• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
• History of gastrointestinal surgery, or evidence of disease that may influence the outcome of the study, within 4 weeks before dosing (e.g., psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism)
• Participated in, is currently participating in, or is seeking treatment for substance- or alcohol-related disorders (excluding nicotine and caffeine)
• Heavy smokers (≥20 cigarettes or eCigarettes per day on average in the past 30 days before Screening), chews tobacco, uses a nicotine transdermal patch (including nicotine-containing products), or is unable to abstain from smoking for at least 8 hours during any day
• Participant is a habitual napper (i.e., habitually naps more than 3 times per week)
• ≥15 on Apnea subscale
• ≥19 on Insomnia subscale if and only if also ≥15 on Impact subscale
• ≥7 on Narcolepsy subscale
• ≥7 on Restless Legs Syndrome (RLS) or Periodic Limb Movement Disorder (PLMD) subscale
• ≥8 on Circadian Rhythm subscale
• ≥7 on Sleepwalking subscale
• ≥3 on Item 32 and ≥9 on Items 33 to 35 (i.e., on nightmare subscale)

Sponsors & Collaborators

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

Study Sites (1)

INC Research Toronto, Inc.

Toronto, M5V 2T3, Canada

Location

Related Publications (1)

• Landry I, Hall N, Alur J, Filippov G, Reyderman L, Setnik B, Henningfield J, Moline M. Acute Cognitive Effects of the Dual Orexin Receptor Antagonist Lemborexant Compared With Suvorexant and Zolpidem in Recreational Sedative Users. J Clin Psychopharmacol. 2022 Jul-Aug 01;42(4):374-382. doi: 10.1097/JCP.0000000000001562. Epub 2022 Jun 24.

  PMID: 35748777 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Zolpidem; suvorexant; lemborexant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 17, 2017
• Study Start: April 19, 2017
• Primary Completion: July 4, 2018
• Study Completion: July 4, 2018
• Last Updated: June 29, 2020

Record last verified: 2018-07

Locations

CA (1)