Study of the Effect of Armodafinil Treatment in Healthy Subjects With Excessive Sleepiness Associated With Jet Lag Disorder

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-group study of armodafinil and placebo treatment in healthy subjects with excessive sleepiness associated with jet lag disorder.

Official Title
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A 3-Day, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Effect of Armodafinil Treatment (50 and 150 mg/Day) in Healthy Subjects With Excessive Sleepiness Associated With Jet Lag Disorder

Conditions
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Excessive Sleepiness

Intervention / Treatment
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* Drug: armodafinil
* Drug: armodafinil
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: History of jet lag symptoms during the past 5 years. The subject is in good health, as determined by a medical and psychiatric history, medical examination, clinical laboratory test results, and electrocardiography (ECG) and physical examination findings. Women of childbearing potential must be abstinent or use a medically accepted method of contraception, and must continue use of this method for the duration of the study (and for 30 days after participation in the study). The subject is willing to comply with study restrictions and remain at the study center overnight, as required. The subject must agree to refrain from alcohol use during the study. The subject has a valid U.S. passport Key Exclusion Criteria: The subject has a history (past 12 months) or diagnosis of narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), shift work sleep disorder (SWSD), or any other sleep disorder associated with excessive daytime sleepiness; or the subject has a history or current diagnosis of hypersomnia, insomnia, or sleep disorder. The subject has any serious acute or chronic cardiovascular, pulmonary, gastrointestinal, neurological, endocrine or renal illness (including diabetes mellitus), hepatitis, asthma, chronic obstructive pulmonary disease (COPD), or any other clinically relevant significant medical condition. The subject has a history of any cutaneous drug reaction or drug hypersensitivity, or any clinically significant hypersensitivity reaction, or multiple allergies. The subject has a history of deep vein thrombosis (DVT). The subject has known human immunodeficiency virus (HIV). The subject is pregnant or lactating. The subject has used nicotine within the last 3 months. The subject has a history of seizures, except for a single febrile seizure. The subject has a psychiatric disorder that would affect participation in the study or full compliance with study procedures. The subject has a clinically significant deviation from normal in clinical laboratory results, vital signs measurements, or physical examination findings. The subject used any prescription or over the counter drugs disallowed by the protocol within 7 days of screening visit 2 (i.e., stimulants, hypnotics). The subject has used an investigational drug within 1 month before the screening visit. The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion. The subject has a known hypersensitivity to armodafinil or modafinil, or any other component of the study drug tablets.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>armodafinil - dosage of 50 mg/day | Drug: armodafinil<br>* 50 mg/day orally, once daily in the morning for 3 days<br>|
| Experimental: 2<br>armodafinil - dosage of 150 mg/day | Drug: armodafinil<br>* 150 mg/day orally, once daily in the morning for 3 days<br>|
| Placebo Comparator: 3<br>matching placebo | Drug: placebo<br>* placebo tablets, once daily in the morning for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sleep Latency (Minutes) From the Multiple Sleep Latency Test (MSLT)- Average of Four Scheduled Naps Across Days 1 and 2 | MSLT is an assessment that measures likelihood of falling asleep. Mean Sleep Latency measures the time to fall asleep. On Treatment Days 1 and 2 the subject was instructed on 4 occasions to attempt to fall asleep. Each MSLT nap continued until 3 consecutive 30-second epochs of stage 1 sleep were reached, or any 30 second epoch of stage 2, 3, 4 or rapid eye movement sleep was reached. Each nap was terminated after 20 minutes if no sleep occured. Average sleep latency for the 4 naps was tabulated across days 1 and 2. Sleep latency was measured from lights out to first epoch scored as sleep. | Days 1 and 2 | 
| Average of Patient Global Impression of Severity (PGI-S) of General Condition Ratings Across Days 1 and 2 | The PGI-S rating scale is the patient's assessment of their general condition. The subject rates their overall condition according to the 7 following categories: 1=normal (no sign of illness), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill. The term ill refers here to any symptoms of jet lag and overall feeling. Symptoms may include sleepiness, irritability, malaise, gastrointestinal disturbance, and level of performance. The average of PGI-S ratings across days 1 and 2 are presented here. | Days 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average of Scores Across Days 1 and 2 in the Karolinska Sleepiness Scale (KSS) | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS least squares mean score across days 1 and 2 are reported here. | Days 1 and 2 | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) at Day 1 | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS least squares mean score across day 1 is reported here. | Day 1 | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) at Day 2 | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS Least squares mean score as measured on day 2 is reported here. | Day 2 | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) at Day 3 | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS least squares mean score as measured on day 3 is reported here. | Day 3 | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) Collected at Bedtime at Baseline | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS mean score as measured at Baseline, collected at bedtime, is reported here. | Baseline prior to starting study medication | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) Collected at Bedtime at Day 1 | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS mean score as measured on day 1, collected only at bedtime, is reported here. | Day 1 bedtime | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) Collected at Bedtime at Day 2 | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS mean score as measured on day 2, collected only at bedtime, is reported here. | Day 2 bedtime | 
| Mean Scores From the Karolinska Sleepiness Scale (KSS) Collected at Bedtime at Day 3 | The Karolinska Sleepiness Scale is a validated subject-rated instrument for measuring sleepiness, based on a scale from 1 to 9 (with 1 indicating very alert and 9 indicating very sleepy, great effort to stay awake, fighting sleep). The KSS was administered 5 times during the day; before each MSLT nap and before bedtime. The KSS mean score as measured on day 3, collected only at bedtime, is reported here. | Day 3 bedtime | 
| Mean Ratings From the Mean Sleep Latency of the Multiple Sleep Latency Tests (MSLT) at Baseline | MSLT measures the likelihood of falling asleep. Mean Sleep Latency measures the time to fall asleep (in minutes). On Treatment Days 1 and 2 the subject was instructed on 4 occasions to attempt to fall asleep. Each MSLT nap continued until 3 consecutive 30-sec epochs of stage 1 sleep were reached, or any 30 sec epoch of stage 2, 3, 4 or rapid eye movement sleep was reached. Each nap was terminated after 20 min if no sleep occurred. Sleep latency was measured from lights out to first epoch scored as sleep. Mean sleep latency from the MSLT at Baseline (Screening Day 2) is presented here. | Baseline defined as Screening Visit 2 within 8 weeks prior to Treatment Day 1 | 
| Mean Sleep Latency (Minutes) From the Multiple Sleep Latency Tests (MSLT) at Day 1 | MSLT measures likelihood of falling asleep. Mean Sleep Latency measures the time to fall asleep (in minutes). On Treatment Days 1 and 2 the subject was instructed on 4 occasions to attempt to fall asleep. Each MSLT nap continued until 3 consecutive 30-sec epochs of stage 1 sleep were reached, or any 30 sec epoch of stage 2, 3, 4 or rapid eye movement sleep was reached. Each nap was terminated after 20 min if no sleep occurred. Sleep latency was measured from lights out to first epoch scored as sleep. Least squares mean sleep latency from the MSLT at day 1 is presented here. | Day 1 | 
| Mean Sleep Latency (Minutes) From the Multiple Sleep Latency Tests (MSLT) at Day 2 | MSLT measures likelihood of falling asleep. Mean Sleep Latency measures the time to fall asleep (in minutes). On Treatment Days 1 and 2 the subject was instructed on 4 occasions to attempt to fall asleep. Each MSLT nap continued until 3 consecutive 30-sec epochs of stage 1 sleep were reached, or any 30 sec epoch of stage 2, 3, 4 or rapid eye movement sleep was reached. Each nap was terminated after 20 min if no sleep occurred. Sleep latency was measured from lights out to first epoch scored as sleep. Least Squares Mean sleep latency from the MSLT at day 2 is presented here. | Day 2 | 
| Mean Sleep Latency (Minutes) From the Multiple Sleep Latency Tests (MSLT) at Day 3 | MSLT measures likelihood of falling asleep. Mean Sleep Latency measures the time to fall asleep (in minutes). On Treatment Days 1 and 2 the subject was instructed on 4 occasions to attempt to fall asleep. Each MSLT nap continued until 3 consecutive 30-sec epochs of stage 1 sleep were reached, or any 30 sec epoch of stage 2, 3, 4 or rapid eye movement sleep was reached. Each nap was terminated after 20 min if no sleep occurred. Sleep latency was measured from lights out to first epoch scored as sleep. Least Squares Mean sleep latency from the MSLT at day 3 is presented here. | Day 3 | 
| Mean Patient Global Impression of Severity of General Condition Ratings at Baseline | The PGI-S rating scale is the patient's assessment of general condition. The subject rates their overall condition according to the 7 following categories: 1=normal (no sign of illness), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill. The term ill refers to symptoms of jet lag including excessive sleepiness, irritability, malaise, gastrointestinal disturbance, and poor performance. The least squares mean of PGI-S ratings at Baseline is presented here. | Baseline, prior to start of study drug dosing | 
| Mean Patient Global Impression of Severity of General Condition Ratings at Day 1 | The PGI-S rating scale is the patient's assessment of general condition. The subject rates their overall condition according to the 7 following categories: 1=normal (no sign of illness), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill. The term ill refers to symptoms of jet lag including excessive sleepiness, irritability, malaise, gastrointestinal disturbance, and poor performance. The least squares mean of PGI-S ratings at day 1 is presented here. | Day 1 | 
| Mean Patient Global Impression of Severity of General Condition Ratings at Day 2 | The PGI-S rating scale is the patient's assessment of general condition. The subject rates their overall condition according to the 7 following categories: 1=normal (no sign of illness), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill. The term ill refers to symptoms of jet lag including excessive sleepiness, irritability, malaise, gastrointestinal disturbance, and poor performance. The least squares mean of PGI-S ratings at day 2 is presented here. | Day 2 | 
| Mean Patient Global Impression of Severity of General Condition Ratings at Day 3 | The PGI-S rating scale is the patient's assessment of general condition. The subject rates their overall condition according to the 7 following categories: 1=normal (no sign of illness), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill. The term ill refers to symptoms of jet lag including excessive sleepiness, irritability, malaise, gastrointestinal disturbance, and poor performance. The least squares mean of PGI-S ratings at day 3 is presented here. | Day 3 | 
| Change in State and Trait Anxiety Inventory Total Score From Baseline to Endpoint | The State and Trait Anxiety Inventory is a validated self-reporting instrument used to assess anxiety in adults. The inventory consists of 2 scales, state anxiety, which evaluates how the subject feels currently (transient anxiety), and trait anxiety, which evaluates how the subject feels generally (general tendency towards anxiety). Each scale consists of 20 questions, and a higher score indicates greater anxiety. Scores range from 20 (no anxiety) to 80 (maximum anxiety). The change in total score from Baseline to endpoint is presented here. | Endpoint defined as either Day 3 or last observation after baseline | 
| Change in State and Trait Anxiety Inventory Total Score From Baseline to Day 1 | The State and Trait Anxiety Inventory is a validated self-reporting instrument used to assess anxiety in adults. The inventory consists of 2 scales, state anxiety, which evaluates how the subject feels currently (transient anxiety), and trait anxiety, which evaluates how the subject feels generally (general tendency towards anxiety). Each scale consists of 20 questions, and a higher score indicates greater anxiety. Scores range from 20 (no anxiety) to 80 (maximum anxiety). The change in total score from Baseline to Day 1 is presented here. | Day 1 | 
| Change in State and Trait Anxiety Inventory Total Score From Baseline to Day 2 | The State and Trait Anxiety Inventory is a validated self-reporting instrument used to assess anxiety in adults. The inventory consists of 2 scales, state anxiety, which evaluates how the subject feels currently (transient anxiety), and trait anxiety, which evaluates how the subject feels generally (general tendency towards anxiety). Each scale consists of 20 questions, and a higher score indicates greater anxiety. Scores range from 20 (no anxiety) to 80 (maximum anxiety). The change in total score from Baseline to Day 2 is presented here. | Day 2 | 
| Change in State and Trait Anxiety Inventory Total Score From Baseline to Day 3 | The State and Trait Anxiety Inventory is a validated self-reporting instrument used to assess anxiety in adults. The inventory consists of 2 scales: state anxiety, which evaluates how the subject feels currently (transient anxiety), and trait anxiety, which evaluates how the subject feels generally (general tendency towards anxiety). Each scale consists of 20 questions, and a higher score indicates greater anxiety. Scores range from 20 (no anxiety) to 80 (maximum anxiety). The change in total score from Baseline to Day 3 is presented here. | Day 3 | 
| Mean Change From Baseline to Endpoint in Total Sleep Time as Measured by Nocturnal Polysomnography | Nocturnal Polysomnography records normal and abnormal physiological activity during an entire night's sleep. It documents the adequacy of sleep, including frequency duration, and total amount of stage 1-2, stage 3-4 (slow wave sleep), rapid eye movement sleep, and apnea/hypopnea index. Data presented here represents the difference in mean total sleep time overnight from Baseline to Day 2 as recorded by nocturnal polysomnography. | Baseline and Day 2 (Endpoint) | 
| Mean Change From Baseline to Endpoint in Latency to Persistent Sleep as Measured by Nocturnal Polysomnography | Nocturnal Polysomnography records normal and abnormal physiological activity during an entire night's sleep. It documents the adequacy of sleep, including frequency duration, and total amount of stage 1-2, stage 3-4 (slow wave sleep), rapid eye movement sleep, and apnea/hypopnea index. Data presented here represents the difference in mean latency to persistent sleep from Baseline to Day 2 as recorded by nocturnal polysomnography. | Baseline and Day 2 (Endpoint) | 
| Mean Change in Sleep Efficiency From Baseline To Endpoint as Measured by Nocturnal Polysomnography | Nocturnal Polysomnography records normal and abnormal physiological activity during an entire night's sleep. It documents the adequacy of sleep, including frequency duration, and total amount of stage 1-2, stage 3-4 (slow wave sleep), rapid eye movement sleep, and apnea/hypopnea index. Data presented here represents the difference in mean sleep efficiency from Baseline to Day 2 as recorded by nocturnal polysomnography. Sleep efficiency is defined as the ratio of time spent asleep (total sleep time) to the amount of time in bed. | Baseline and Day 2 (Endpoint) | 
| Mean Change From Baseline to Endpoint in Wake Time After Sleep Onset as Measured by Nocturnal Polysomnography | Nocturnal Polysomnography records normal and abnormal physiological activity during an entire night's sleep. It documents the adequacy of sleep, including frequency duration, and total amount of stage 1-2, stage 3-4 (slow wave sleep), rapid eye movement sleep, and apnea/hypopnea index. Data presented here represents the difference in mean wake time after sleep onset (time spent awake from sleep onset to final awakening) from Baseline to Day 2 as recorded by nocturnal polysomnography. | Baseline and Day 2 (Endpoint) |