Sleep deprivation slows reaction time, reduces vigilance and impairs judgment and information
processing. Chronic effects include metabolic dysfunction, cardiovascular disease and cancer.
Sleep deprivation affects quality of life when it causes errors in judgment, whether these
occur behind the wheel of an automobile or in a hospital. Armodafinil, a non-amphetamine
wakefulness promoting medication, indicated for excessive sleepiness associated with
obstructive sleep apnea, narcolepsy, and shift work sleep disorder is used to mitigate the
effects of sleep deprivation.
This study will characterize the effect of armodafinil on driving simulator performance. The
effects of armodafinil compared to placebo will be studied in a double blind crossover trial
involving 10 healthy subjects with serial assessments at baseline and after extensive sleep
deprivation. Using simultaneous electroencephalogram (EEG) recording during simulated driving
and neurocognitive assessments of vigilance, the relationship between brain activity and
cognitive performance will be established.
On the first study day, the subjects will come to the Clinical Research Center (CRC) early in
the morning. In the first 90 minutes (acclimation session) of the study day EEG electrodes
will be applied and EEG signals will be measured continuously throughout the session.
Subjects will be instructed of the controls and operation of the driving simulator and
perform a 10 minute test drive to familiarize with it. Afterwards they will perform a battery
of cognitive tests including the Motor Praxis Task, the Visual Object Learning Test, the
Fractal-2-Back, the Abstract Matching, the Line Orientation Test, the Digit-Symbol
Substitution Task, the Balloon Analog Risk Test, and the Psychomotor Vigilance Test to get
familiar with the cognitive tests. The cognitive battery will last approximately 25 minutes.
The collected data of the conditioning session won't be part of the analysis. The purpose of
the session is that subjects adapt to the measures.
Following the acclimation session, the resting baseline for the subjects will be measured
which will consist of a simultaneous assessment of cognitive performance and brain activity.
The subjects will first drive for 30 minutes on the driving simulator to establish a resting
baseline of the driving performance. Afterwards a resting baseline for cognitive tests will
be established to measure attention, vigilance, risk-taking and decision-making. EEG will be
recorded concurrently during driving and cognitive tests. No blood samples will be taken
during the assessment of the resting baseline. Subjects will be discharged from the CRC after
completion of the baseline session (approximately 2 hours) until the evening. During this
time subjects are not allowed to sleep and they will be informed to not consume any caffeine
containing products (e.g. Red Bull, coffee). Upon return to the CRC, the subjects will be
sleep deprived and supervised by at least one of the study coordinators and at least one
additional person to make sure the subjects don't fall asleep during the night.
The following day, 24 hours after the resting baseline session, the fatigue baseline session
will start. Sessions of resting baseline and fatigue baseline will be scheduled for the same
time of day on two consecutive days to account for circadian alignment. The testing procedure
will be identical to the resting baseline session that means subjects will drive for 60
minutes on the driving simulator and perform the same cognitive tests as in the baseline
session. After completion of the fatigue baseline session, the study drug (armodafinil 250 mg
or placebo) will be administered. To determine the pharmacokinetics, blood samples will be
obtained prior to drug dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
through an intravenous catheter placed in the arm vein of the subjects. After study drug
intake subjects will perform 5 sessions on the driving simulator consisting of 30-minute
drives. The same battery of tests performed at baseline will be performed between the drives.
The tested cognitive abilities play an important role during driving and the investigators
will investigate to what extent sleep deprivation alters these abilities and how armodafinil
is able to counter the deteriorating effects of sleep deprivation on these capabilities.
1. Male or females, between age 18 and 35 years of age, inclusive.
2. Body mass index (BMI) from 18.5 to 29.9 kg/m2, inclusive.
3. A valid driver's license.
4. Healthy on the basis of physical examination, medical history, vital signs.
5. Absence of clinically significant abnormalities in the subject's sleep history. The
study physician will base this decision on the Epworth Sleepiness Scale and a
discussion with the subject about his or her sleep history.
6. Female subjects must be postmenopausal (for at least 6 months), surgically sterile, or
abstinent; or, if of childbearing potential and sexually active, be practicing an
effective method of birth control (e.g., intrauterine device, double-barrier method,
male partner sterilization) before entry and throughout the study; have a negative
urine pregnancy test at screening, and a negative urine pregnancy test prior to each
experimental session. Steroidal contraceptives have been shown to interact with the
study drug and are not an acceptable form of contraception for this study (subjects
taking steroidal contraceptive drugs are ineligible for this study).
7. Agree not to consume any alcohol 24 hours prior to any study session and until
discharge from the unit.
8. Agree not to consume any grapefruit or grapefruit juice 24 hours prior to dosing and
until discharge from the unit.
9. Agree not to use armodafinil or modafinil-containing medications 2 weeks prior to or
during any study session (aside from what is administered for the study).
10. Agree not to use any other medication that acts on the central nervous system
(prescription or nonprescription) 1 week prior to or during any study session
(caffeine is the only exception, subjects are recommended to avoid caffeine for one
week prior to a study session, but are required to avoid caffeine for 24 hours prior
to and during a study session).
11. The subject is able to understand and comply with protocol requirements, instructions
and protocol-stated restrictions and is likely to complete the study as planned.
Subject is willing to provide informed consent.
1. History of current significant medical illness including (but not limited to)
cardiovascular thrombotic events, myocardial infarction, stroke or other cardiac
disease, hypertension, peptic ulcer disease or gastrointestinal bleeding,
hematological disease, bronchospastic respiratory disease, asthma, diabetes mellitus,
renal or hepatic insufficiency, psychiatric disorders, or any other illness that the
investigator considers should exclude the subject.
2. Subjects who have a clinically significant sleep abnormality.
3. Subjects who are shift workers.
4. Evidence of use of drugs of abuse (including but not limited to barbiturates, opiates,
cocaine, cannabinoids, amphetamines, and benzodiazepines) assessed via questioning the
5. Subjects that are a smoker and smoke more than 10 cigarettes per day.
6. Known allergies or hypersensitivity to armodafinil or modafinil.
7. The subject has contraindications to take armodafinil.
8. Clinically significant abnormal physical examination, vital signs (e.g. systolic blood
pressure>140 mmHg, diastolic blood pressure>90 mmHg, heart rate >100 bpm and <45 bpm)
or 12-lead ECG (e.g. corrected QT>450 msec) at screening or abnormal vital signs prior
to study drug dosing.
9. The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).
10. Pregnant or breast-feeding.
11. Taking a steroidal contraceptive drug or drugs.
12. Donation of 1 or more units (approximately 450 mL) of blood or acute loss of an
equivalent amount of blood within 60 days prior to study drug administration.
13. Recent history of surgery; within the past 3 months prior to screening.
14. Clinically significant acute illness within 7 days prior to study drug administration.
15. Strenuous exercise that is more excessive than their normal routine, 48 hours prior to
each session, until they are discharged from the unit.
16. Any condition that, in the opinion of the investigator, would compromise the
well-being of the subject or the study or prevent the subject from meeting or
performing study requirements.
17. Unwillingness or inability to follow the procedures outlined in the protocol.
18. Employees of the investigator or study center, with direct involvement in the proposed
study or other studies under the direction of that investigator or study center, as
well as family members of the employees or the investigator.
19. Subjects living outside of Gainesville