A Comparison of the Physiological and Behavioral Effects of Suvorexant and Zolpidem in Healthy Volunteers: A Randomized, Double-blind, Placebo Controlled Study

The primary objective of this study is to evaluate two pharmacotherapeutic approaches to sleep induction, both of which have been shown to be effective hypnotics, but may have unique side effect profiles. These profiles may have markedly different impacts on performance in a military setting. In this randomized, double-blind, placebo controlled study, the side effects of these drugs will be compared - suvorexant, a dual orexin receptor antagonist and zolpidem, a non-benzodiazepine gamma-aminobutyric acid (GABA) A agonist - in healthy controls comparable in age and gender to the target military population.

Study Overview

• Status: Active, not recruiting
• Conditions: Performance Enhancing Product Use
• Intervention / Treatment: Drug: Suvorexant 10 mg; Drug: Placebos; Drug: Zolpidem

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

Healthy males and non-pregnant, non-lactating female volunteers must be between the ages of 18 and 39

• learned English as a first language (inclusive)*.
• To be included in the study, volunteers will have to pass a "Volunteer Comprehension Assessment" with a score of 80% or greater. A maximum of two attempts is permitted. See section 5.7 for details.

• Females of child-bearing potential must be on some form of birth control, if sexually active (e.g., oral contraceptive, condom, intrauterine device, etc.)

  • Volunteers must have learned English as their first language. This is because there are cognitive tests administered during the study that require a mastery of the English language.

Exclusion Criteria

• Self-reported habitual nightly sleep amounts outside the target range of approximately 6-9 hours (i.e., less than 6 hours per night or more than 9 hours per night, on average) (Post-consent Checklist).
• Any use of prescription or over-the-counter sleep aids during the 3-month period prior to screening determined by the examining study medical investigator to be indicative of a potential sleep disorder (e.g., use of a sleep aid for several nights following travel across multiple time zones would not necessarily constitute evidence of a sleep disorder).
• Self-reported nighttime lights-out times earlier than 2000 or later than 0100 during weeknights (Sunday through Thursday) (Post-consent Checklist)
• Self-reported morning wake-up times earlier than 0500 or later than 0900 during weekdays (Monday through Friday) (Post-consent Checklist)
• Self-reported habitual napping (> 3 times a week) in conjunction with normal sleep habits (Post-consent Checklist).
• Self-reported symptoms suggestive of a sleep disorder (including but not limited to insomnia, narcolepsy, sleep disordered breathing/sleep apnea, idiopathic hypersomnia, restless leg syndrome, parasomnias, REM behavior disorder, etc.) (Post-Consent Checklist, Medical History/Exam form; Berlin Questionnaire); history of a sleep disorder (Medical History and Examination) or evidence of such from a prior polysomnographic assessment.
• Objective evidence of narcolepsy + cataplexy using the Ullanlinna Narcolepsy Scale
• Objective evidence of insomnia using the Insomnia Severity Index.
• STATE TRAIT ANXIETY INVENTORY - TRAIT (STAI-T) - Scores above 40.
• MORNING-EVENINGNESS QUESTIONNAIRE -Scores lower than 31 or greater than 69.
• Self-reported caffeine use in excess of 400 mg (e.g., approximately 8 caffeinated sodas or approximately 20 ounces of brewed coffee) per day on average (Post-consent Checklist)
• History of neurologic disorder (including but not limited to epilepsy or another seizure disorder, amnesia, hydrocephalus, Parkinson's disease, MS) (Medical History and Examination form). An infrequent or resolved single neurological event (e.g., childhood seizure, rare sporadic migraine headaches, resolved meningeal infection with no sequelae) may be deemed non-exclusionary at the discretion of the examining study medical investigator.
• Score of 14 or above on the Beck Depression Inventory (BDI form)
• History of cardiovascular disease (including but not limited to arrhythmias, valvular heart disease, congestive heart failure, history of myocardial infarction) (Medical History/Exam form)
• Underlying acute or chronic pulmonary disease requiring daily inhaler use (Medical History /Exam form)
• Kidney disease or significant kidney abnormalities (Medical History/Exam form, laboratory results) as determined by examining study medical investigator.
• Liver disease or significant liver abnormalities (Medical History/Exam form, laboratory results) as determined by examining study medical investigator.
• Self-reported history of psychiatric disorder requiring hospitalization or psychiatric medication for more than 6 months (Medical History/Exam form)
• Self-reported or suspected use of products or drugs that cannot be safely discontinued during in-laboratory phases, to be determined on a case-by-case basis by the examining study medical investigator (Medical History/Exam form).
• Self-reported or suspected heavy alcohol use (minimum limit to define heavy alcohol use is 14 drinks per week or as determined by the examining study medical investigator).
• Self-reported or suspected regular nicotine use (or addiction) (defined as more than 1 cigarette or equivalent per week) within the last 1 year.
• Self-reported or suspected current use of other illicit drugs (including but not limited to benzodiazepines, amphetamines, cocaine, marijuana) (Medical History/Exam form)

Positive urine pregnancy result

• Positive salivary alcohol screening result
• Self-reported or suspected current breast-feeding or collecting breast-milk (Medical History/Exam form)
• Resting blood pressure above 140/90 or resting pulse > 110 beats per minute (Medical History/Exam form) Note that if a repeat measurement is within range, volunteer will not be excluded.
• BMI ≥ 30 (Obese Class I or greater) (Medical History/Exam form)
• Clinically significant values (as determined by the reviewing study medical investigator and the table below) for any hematology or chemistry parameter included in the screening bloodwork.
• Positive urine nicotine/cotinine result during screening visit (NicCheckTM I test strip results)
• Positive urine drug screen result
• Inability to read and sign consent
• Failure to obtain required approved official leave to participate
• Presence of features that may increase risk and/or discomfort during the cold pressor task. These include: past cramp attacks or blackouts, chilblains, open skin wounds, fracture of the hands, and skin and peripheral vascular diseases (to include but not limited to Raynaud's disease.
• As prisoners will not be recruited and are not eligible for participation in this study, any participant that becomes incarcerated during Phase 1 will result in termination from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Suvorexant Arm; 10 mg of Suvorexant	Drug: Suvorexant 10 mg; 10 mg of suvorexant; Drug: Placebos; Avicel
Active Comparator: Zolpidem Arm; 5 mg of Zolpidem	Drug: Placebos; Avicel; Drug: Zolpidem; 5 mg of zolpidem
Placebo Comparator: Placebo; 10mg of Avicel	Drug: Placebos; Avicel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
consolidation of episodic memory	presentation of word lists	5 days
psychomotor vigilance test	measures reaction time	4 days

Collaborators and Investigators

• Sponsor: Walter Reed Army Institute of Research (WRAIR)

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): November 21, 2024
• Study Completion (Estimated): December 12, 2025

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Hypnotics and Sedatives; GABA Agents; GABA-A Receptor Agonists; GABA Agonists; Zolpidem; Suvorexant
• Other Study ID Numbers: WRAIR #2492

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No