Trial Outcomes & Findings for Study to Evaluate Armodafinil Treatment in Improving Prefrontal Cortical Activation and Working Memory Performance (NCT NCT00711516)

Results Overview

The primary outcome was the change from baseline in number of contiguous activated voxels in the dorsolateral prefrontal cortex (DLPFC) on functional magnetic resonance imaging (fMRI) at Week 2(or last observation after baseline). Each voxel is compared to the reference wave form. If it differs from that value p\<0.05, the voxel is considered active. fMRI is a brain imaging technique that identifies neuronal activation related to specific tasks or sensory stimulation. Increased neuronal activity increases blood flow and oxygen content to the activated part of the brain, altering fMRI signal.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

Baseline and Endpoint (Week 2 or last observation after baseline)

Results posted on

2013-07-19

Participant Flow

Participant milestones

Participant milestones
Measure	Armodafinil (200 mg/Day) Armodafinil was titrated during the double-blind treatment period starting with 50 mg/day (1 tablet) on Day 1, increasing to 100 mg/day (2 tablets) on day 2, 150 mg/day (3 tablets) on day 5, and 200 mg/day (4 tablets) on day 8, which was continued for the remainder of the 2-week double-blind treatment period.	Placebo Placebo tablets matching the armodafinil tablets were titrated during the double-blind treatment period starting with 1 tablet/day on Day 1, increasing to 2 tablets/day on day 2, 3 tablets/day on day 5, and 4 tablets/day on day 8, which was continued for the remainder of the 2-week double-blind treatment period.
Overall Study STARTED	21	19
Overall Study COMPLETED	20	16
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Armodafinil (200 mg/Day) Armodafinil was titrated during the double-blind treatment period starting with 50 mg/day (1 tablet) on Day 1, increasing to 100 mg/day (2 tablets) on day 2, 150 mg/day (3 tablets) on day 5, and 200 mg/day (4 tablets) on day 8, which was continued for the remainder of the 2-week double-blind treatment period.	Placebo Placebo tablets matching the armodafinil tablets were titrated during the double-blind treatment period starting with 1 tablet/day on Day 1, increasing to 2 tablets/day on day 2, 3 tablets/day on day 5, and 4 tablets/day on day 8, which was continued for the remainder of the 2-week double-blind treatment period.
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	0	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

Study to Evaluate Armodafinil Treatment in Improving Prefrontal Cortical Activation and Working Memory Performance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Armodafinil (200 mg/Day) n=21 Participants Armodafinil was titrated during the double-blind treatment period starting with 50 mg/day (1 tablet) on Day 1, increasing to 100 mg/day (2 tablets) on day 2, 150 mg/day (3 tablets) on day 5, and 200 mg/day (4 tablets) on day 8, which was continued for the remainder of the 2-week double-blind treatment period.	Placebo n=19 Participants Placebo tablets matching the armodafinil tablets were titrated during the double-blind treatment period starting with 1 tablet/day on Day 1, increasing to 2 tablets/day on day 2, 3 tablets/day on day 5, and 4 tablets/day on day 8, which was continued for the remainder of the 2-week double-blind treatment period.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	49.9 years STANDARD_DEVIATION 8.98 • n=5 Participants	50.7 years STANDARD_DEVIATION 7.95 • n=7 Participants	50.3 years STANDARD_DEVIATION 8.41 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	19 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Efficacy analyses were performed on the full analysis dataset which includes those patients in the safety analysis set who had at least 1 post baseline primary efficacy assessment.

The primary outcome was the change from baseline in number of contiguous activated voxels in the dorsolateral prefrontal cortex (DLPFC) on functional magnetic resonance imaging (fMRI) at Week 2(or last observation after baseline). Each voxel is compared to the reference wave form. If it differs from that value p\<0.05, the voxel is considered active. fMRI is a brain imaging technique that identifies neuronal activation related to specific tasks or sensory stimulation. Increased neuronal activity increases blood flow and oxygen content to the activated part of the brain, altering fMRI signal.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in Number of Contiguous Activated Voxels Meeting Predefined Threshold in Dorsolateral Prefrontal Cortex (DLPFC) on Functional Magnetic Resonance Imaging (fMRI) as a Measure of Prefrontal Cortical Activation	-1932.3 Activated voxels Standard Deviation 2993.8	-2428.1 Activated voxels Standard Deviation 5023.53

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline.

The 2-Back is a verbal working memory test in which random letters are presented visually every 4 sec, with each stimulus lasting 500 msec. Subjects are asked to make a yes/no response following each letter indicating whether it was the same or different from the letter presented two earlier. The load on working memory was the ordering, retention, updating, and manipulation of 2 letters and consideration of the relationship to a 3rd newly presented letter, which could have been a target or a nontarget. The change from baseline in response latency at endpoint is presented here.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in Mean Response Latency in the 2-Back Working Memory Test at Endpoint - Mean Performance Speed	2.3 Milliseconds (ms) Standard Deviation 78.94 • Interval -171.9 to 181.3	-59.0 Milliseconds (ms) Standard Deviation 112.69 • Interval -258.4 to 89.1

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

The outcome was the change from baseline in number of contiguous activated voxels in the anterior cingulate cortex (ACC) on functional magnetic resonance imaging (fMRI) at Week 2(or last observation after baseline). Each voxel is compared to the reference wave form. If it differs from that value p\<0.05, the voxel is considered active. fMRI is a brain imaging technique that identifies neuronal activation related to specific tasks or sensory stimulation. Increased neuronal activity increases blood flow and oxygen content to the activated part of the brain, altering fMRI signal.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Contiguous Activated Voxels Meeting the Predefined Threshold in the Anterior Cingulate Cortex (ACC)	-107.3 Activated Voxels Standard Deviation 367.92	-206.5 Activated Voxels Standard Deviation 340.56

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

The outcome was the change from baseline in number of contiguous activated voxels in the posterior parietal cortex (PPC) on functional magnetic resonance imaging (fMRI) at Week 2(or last observation after baseline). Each voxel is compared to the reference wave form. If it differs from that value with p\<0.05, the voxel is considered active. fMRI is a brain imaging technique that identifies neuronal activation related to specific tasks or sensory stimulation. Increased neuronal activity increases blood flow and oxygen content to the activated part of the brain, altering fMRI signal.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Contiguous Voxels Meeting the Predefined Threshold in the Posterior Parietal Cortex (PPC)	-595.0 Activated voxels Standard Deviation 1251.79	-773.3 Activated voxels Standard Deviation 1693.48

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set

The outcome was the change from baseline in number of contiguous activated voxels in the thalamus on functional magnetic resonance imaging (fMRI) at Week 2(or last observation after baseline). Each voxel is compared to the reference wave form. If it differs from that value significantly (p\<0.05), the voxel is considered active. fMRI is a brain imaging technique that identifies neuronal activation related to specific tasks or sensory stimulation. Increased neuronal activity increases blood flow and oxygen content to the activated part of the brain, altering fMRI signal.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Contiguous Activated Voxels Meeting the Predefined Threshold in the Thalamus	-841.7 Activated voxels Standard Error 401.77	-1417.9 Activated voxels Standard Error 638.48

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy evaluation after baseline

The PRM test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) assesses episodic memory by a patient's ability to encode and recognize visual information. Patterns appear sequentially on the screen, and patients are instructed to remember them. Immediately afterwards a recognition test is performed, in which each pattern shown earlier is presented with another pattern of similar form and color. Patient has to touch the pattern seen earlier. Change from baseline to endpoint in % correct responses with immediate recall is presented. Subjects complete 24 trials per assessment.

Outcome measures

Outcome measures
Measure	Armodafinil n=24 trials Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=24 trials Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Pattern Recognition Memory (PRM) Percent Correct (Immediate) From the CANTAB Battery-Change From Baseline to Endpoint	-0.1 Percent correct trials Standard Deviation 6.56	3.2 Percent correct trials Standard Deviation 6.77

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy evaluation after baseline

The PRM test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) assesses episodic memory as measured by a patient's ability to encode and recognize visual information. Patterns appear sequentially on the screen, and patients are instructed to remember them. Twenty minutes following the immediate recognition test, another "delayed" recognition test is performed, featuring the same stimuli as in the first phase. The change from baseline to endpoint in percent correct responses of this delayed test are presented here. Subjects complete 24 trials per assessment.

Outcome measures

Outcome measures
Measure	Armodafinil n=24 Trials Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=24 Trials Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Pattern Recognition Memory (PRM) Percent Correct (Delayed) From the CANTAB Battery-Change From Baseline to Endpoint	0.4 Percent correct trials Standard Deviation 12.34	-1.1 Percent correct trials Standard Deviation 10.70

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

The RTI is a measure of simple and choice reaction time, movement time and spatio-temporal vigilance during simple and 5 choice reaction time trials. This task also permits measurement of anticipatory/premature responding and perseverative responding. The patient responded to a yellow spot appearing on the screen by letting go of the press pad and touching the location in which the spot appeared. The yellow spot appeared in any 1 of 5 locations in the 5 choice reaction time phase. The change from baseline to endpoint in median correct latency is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Reaction Time Index (RTI) Median Correct Latency, Five Choice Test From the CANTAB Battery-Change From Baseline to Endpoint	-6.5 Milliseconds (ms) Interval -54.0 to 47.0	-12.5 Milliseconds (ms) Interval -252.0 to 44.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

The RTI is a measure of simple and choice reaction time, movement time and spatio-temporal vigilance during simple and 5 choice reaction time trials. This task also permits measurement of anticipatory/premature responding and perseverative responding. The patient responded to a yellow spot appearing on the screen by letting go of the press pad and touching the location in which the spot appeared. The yellow spot appeared in a single location during the simple reaction time phase. The change from baseline to endpoint in median correct latency is presented here.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Reaction Time Index (RTI) Median Correct Latency, One Choice Test From the CANTAB Battery-Change From Baseline to Endpoint	-13.5 Milliseconds (ms) Interval -45.0 to 37.0	-4.5 Milliseconds (ms) Interval -224.0 to 39.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline.

OTS is a spatial planning test based on Tower of London test and the CANTAB Stockings of Cambridge test, and measures frontal lobe function. Subject is shown 2 displays containing 3 colored balls and a row of boxes containing numbers. The patient was shown one demonstration problem and then had to solve 3 additional problems (easy). The problems increased in complexity, from one to six moves. With additional problems subject had to work out how many moves the solutions required in their heads (hard). Change from baseline to endpoint in Mean correct latency for the easy problems is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
One Touch Stockings of Cambridge (OTS) Mean Correct Latency, (Easy) From the CANTAB Battery-Change From Baseline to Endpoint	-787.9 Milliseconds (ms) Standard Deviation 1198.06	-666.7 Milliseconds (ms) Standard Deviation 1751.66

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

OTS is a spatial planning test based on Tower of London test and the CANTAB Stockings of Cambridge test, and measures frontal lobe function. Subject is shown 2 displays containing 3 colored balls and a row of boxes containing numbers. The patient was shown one demonstration problem and then had to solve 3 additional problems (easy). The problems increased in complexity, from one to six moves. With additional problems subject had to work out how many moves the solutions required in their heads (hard). Change from baseline to endpoint in Mean correct latency for the hard problems is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
One Touch Stockings of Cambridge (OTS) Mean Correct Latency, (Hard) From the CANTAB Battery-Change From Baseline to Endpoint	-733.3 Milliseconds (ms) Standard Deviation 8352.4	-6898.1 Milliseconds (ms) Standard Deviation 8708.46

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy measure after baseline

OTS is a spatial planning test based on the Tower of London and the CANTAB Stockings of Cambridge test, and measures frontal lobe function. Patient shown 2 displays containing 3 colored balls and a row of boxes containing numbers. The patient is shown one demonstration problem and then solves 3 additional problems (easy). Problems increased in complexity, from one to six moves. With additional problems (hard) the patient has to work out how many moves the solutions required in their heads. Mean change from Baseline to endpoint in number of choices to correct for easy problems is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
One Touch Stockings of Cambridge (OTS) Mean Choices to Correct, (Easy) From the CANTAB Battery-Change From Baseline to Endpoint	0.0 Choices to correct Standard Deviation 0.08	0.0 Choices to correct Standard Deviation 0.17

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

OTS is a spatial planning test based on the Tower of London and the CANTAB Stockings of Cambridge test, and measures frontal lobe function. Patient shown 2 displays containing 3 colored balls and a row of boxes containing numbers. The patient was shown one demonstration problem and then solves 3 additional problems (easy). Problems increased in complexity, from one to six moves. With additional problems (hard) the patient had to work out how many moves the solutions required in their heads. Mean change from baseline to endpoint in number of choices to correct for hard problems is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
One Touch Stockings of Cambridge (OTS) Mean Choices to Correct, (Hard) From the CANTAB Battery-Change From Baseline to Endpoint	-0.2 Choices to correct Standard Deviation 0.29	0.0 Choices to correct Standard Deviation 0.30

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full analysis set defined as subjects who had at least one efficacy evaluation after baseline

The patient's evaluation of excessive daytime sleepiness was measured by the patient reported measure, ESS (Johns1991). The ESS score was based on responses to questions referring to 8 everyday situations (eg, sitting and reading, talking to someone, being stopped in traffic) and reflected a patient's propensity to fall asleep in those situations. The ESS score was derived from the sum of the values from questions corresponding to the 8 situations. Scores for the ESS ranged from 0 to 24, with a higher score indicating a greater daytime sleepiness. Change from baseline to endpoint is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Epworth Sleepiness Scale Change From Baseline to Endpoint	-5.8 Units on a scale Standard Error 1.03	-2.9 Units on a scale Standard Error 1.08

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline

Severity of sleepiness, was assessed by the Clinical Global Impression of Severity (CGI-S) at Baseline. The clinician assessed the change from baseline in the patient's condition, as related to excessive sleepiness, in response to treatment using the CGI-C, which consisted of the following 7 categories and scoring assignments: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. Responders had to be at least minimally improved from Baseline to qualify as a responder at Endpoint.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Clinical Global Impression of Change (CGI-C)- Number of Responders at Endpoint	13 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Population defined as subjects who had at least one efficacy evaluation after baseline.

The MOS-CF6 is an instrument to assess patient self-reported cognitive function. Items were selected to cover 6 relevant aspects of cognitive functioning as follows: confusion, concentration/thinking, attention, memory, reasoning, problem solving, and processing speed. The CF 6 item responses include 6 choices, ranging from "none of the time" to "all of the time." The CF-6 was scored by summing responses across the 6 items and converting the total to a 0 to 100 point scale, with higher scores indicating better cognitive functioning. Change in MOS-CF6 from baseline to endpoint is reported.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Total Score From the Medical Outcomes Study 6-Item Cognitive Function Scale (MOS-CF6)-Change From Baseline to Endpoint	6.1 Units on a scale Standard Error 2.82	-0.2 Units on a scale Standard Error 3.11

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy assessment after baseline.

Functional magnetic resonance imaging (fMRI) is a brain imaging technique that identifies neuronal activation in regions related to specific tasks or sensory stimulation such as language, vision, hearing, and short-term memory. When neuronal activity increases, blood flow increases to that part of the brain with an increase in the oxygen content of the blood. Increase in oxygen content causes the fMRI signal in that part of the brain to change, and is the basis of the BOLD effect. The percent change in BOLD signal from Baseline to 2 weeks or last observation after baseline is presented here.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Blood Oxygenation Level Dependent (BOLD) Signal Intensity - Percent Change From Baseline to Endpoint in the Dorsolateral Prefrontal Cortex (DLPFC)	-0.398 Percentage change in BOLD signal Full Range 4.2761 • Interval -23.439 to 45.139	4.704 Percentage change in BOLD signal Full Range 10.3232 • Interval -43.84 to 94.919

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects with at least one efficacy evaluation after baseline

Functional magnetic resonance imaging (fMRI) is a brain imaging technique that identifies neuronal activation in regions related to specific tasks or sensory stimulation such as language, vision, hearing, and short-term memory. When neuronal activity increases, blood flow increases to that part of the brain with an increase in the oxygen content of the blood. Increase in oxygen content causes the fMRI signal in that part of the brain to change, and is the basis of the BOLD effect. The percent change in BOLD signal from Baseline to 2 weeks or last observation after baseline is presented here.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Blood Oxygenation Level Dependent (BOLD) Signal Intensity - Percent Change From Baseline to Endpoint in the Anterior Cingulate Cortex (ACC)	-1.777 Percent change in BOLD signal Full Range 6.7798 • Interval -38.587 to 99.034	7.148 Percent change in BOLD signal Full Range 9.4912 • Interval -100.0 to 55.958

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy evaluation after baseline

Functional magnetic resonance imaging (fMRI) is a brain imaging technique that identifies neuronal activation in regions related to specific tasks or sensory stimulation such as language, vision, hearing, and short-term memory. When neuronal activity increases, blood flow increases to that part of the brain with an increase in the oxygen content of the blood. Increase in oxygen content causes the fMRI signal in that part of the brain to change, and is the basis of the BOLD effect. The percent change in BOLD signal from Baseline to 2 weeks or last observation after baseline is presented here.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Blood Oxygenation Level Dependent (BOLD) Signal Intensity -Change From Baseline to Endpoint in the Posterior Parietal Cortex (PPC)	3.199 Percent change in Bold signal Full Range 3.2493 • Interval -31.541 to 27.343	-2.021 Percent change in Bold signal Full Range 4.9907 • Interval -30.116 to 32.956

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one efficacy evaluation after baseline

Functional magnetic resonance imaging (fMRI) is a brain imaging technique that identifies neuronal activation in regions related to specific tasks or sensory stimulation such as language, vision, hearing, and short-term memory. When neuronal activity increases, blood flow increases to that part of the brain with an increase in the oxygen content of the blood. Increase in oxygen content causes the fMRI signal in that part of the brain to change, and is the basis of the BOLD effect. The percent change in BOLD signal from Baseline to 2 weeks or last observation after baseline is presented here.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Blood Oxygenation Level Dependent (BOLD) Signal Intensity - Percent Change From Baseline to Endpoint in the Thalamus	16.363 Percent change in BOLD signal Full Range 9.6289 • Interval -41.089 to 98.265	2.099 Percent change in BOLD signal Full Range 7.7566 • Interval -30.301 to 74.962

SECONDARY outcome

Timeframe: Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between the number of voxels activated on fMRI (voxels that differ significantly from reference wave form) in DLPFC versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship Between the Functional Magnetic Resonance Imaging (fMRI) in Dorsolateral Prefrontal Cortex (DLPFC) and 2-Back Working Memory Test - Number of Voxels Activated at Endpoint	0.422 Correlation Coefficient Interval -0.026 to 0.728	-0.445 Correlation Coefficient Interval -0.77 to 0.066

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one efficacy evaluation after baseline

With this outcome measure the correlation between the number of voxels activated on fMRI (voxels that differ significantly from reference wave form) in ACC versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship Between the Functional Magnetic Resonance Imaging (fMRI) in Anterior Cingulate Cortex (ACC) and 2-Back Working Memory Test - Number of Voxels Activated at Endpoint	0.254 Correlation Coefficient Interval -0.213 to 0.626	-0.152 Correlation Coefficient Interval -0.603 to 0.371

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between the number of voxels activated on fMRI (voxels that differ significantly from reference wave form) in PPC versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship Between Functional Magnetic Resonance Imaging (fMRI) in Posterior Parietal Cortex (PPC) and the 2-Back Working Memory Test -Number of Voxels Activated at Endpoint	0.355 Correlation Coefficient Interval -0.104 to 0.689	-0.358 Correlation Coefficient Interval -0.725 to 0.168

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between the number of voxels activated on fMRI (voxels that differ significantly from reference wave form) in the thalamus versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship Between Functional Magnetic Resonance Imaging (fMRI) in the Thalamus and 2-Back Working Memory Test -Number of Voxels Activated at Endpoint	0.405 Correlation Coefficient Interval -0.046 to 0.719	-0.038 Correlation Coefficient Interval -0.524 to 0.467

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between the BOLD signal intensity on fMRI over DLPFC versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship Between the Functional Magnetic Resonance Imaging (fMRI) in Dorsolateral Prefrontal Cortex (DLPFC) and 2-Back Working Memory Test - Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint	-0.122 Correlation Coefficient Interval -0.536 to 0.339	0.789 Correlation Coefficient Interval 0.481 to 0.923

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between the BOLD signal intensity on fMRI in the ACC versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship Between Functional Magnetic Resonance Imaging (fMRI) in Anterior Cingulate Cortex (ACC) and 2-Back Working Memory Test -Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint	0.025 Correlation Coefficient Interval -0.423 to 0.462	-0.012 Correlation Coefficient Interval -0.505 to 0.487

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between the BOLD signal intensity on fMRI in PPC versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship on Functional Magnetic Resonance Imaging (fMRI) in Posterior Parietal Cortex (PPC) and 2-Back Working Memory Test - Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint	0.065 Correlation Coefficient Interval -0.388 to 0.494	0.364 Correlation Coefficient Interval -0.161 to 0.728

SECONDARY outcome

Timeframe: Week 2 or Last Observation after Baseline

Population: Full Analysis Set defined as subjects with at least one observation after baseline

With this outcome measure the correlation between BOLD signal intensity on fMRI in the thalamus versus performance on the 2-back working memory test was evaluated for both Armodafinil and Placebo. Correlation coefficients and P-values are presented for each treatment group.

Outcome measures

Outcome measures
Measure	Armodafinil n=20 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Activation-Performance Relationship on Functional Magnetic Resonance Imaging (fMRI) in the Thalamus and 2-Back Working Memory Test - Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint	-0.029 Correlation Coefficient Interval -0.466 to 0.419	0.582 Correlation Coefficient Interval 0.121 to 0.836

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group Analysis of subjects who were responders on the 2-Back Working Memory Test defined as subjects who had a response latency of \< 713 ms at Endpoint

This is a subgroup analysis of responders on the 2-back working memory test for the number of voxels meeting the predefined threshold in DLPFC. A responder in the 2-back working memory test was defined as a patient showing a response latency of less than 713 ms at endpoint. This is based on baseline data from the matched control population in a functional imaging study in patients with obstructive sleep apnea. The change from Baseline to Endpoint in the number of activated voxels (that differ significantly from reference wave form) for each treatment group among the responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=8 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=4 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the DLPFC on fMRI on the 2 Back Working Memory Test - Change From Baseline-Subgroup-Responders in 2 Back Working Memory Test	-1411.6 Activated voxels Standard Error 1365.62	-1359.0 Activated voxels Standard Error 1146.49

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group Analysis of subjects who were responders on the 2-Back Working Memory Test (had response latency \< 713 ms) at Endpoint

This is a subgroup analysis of responders on the 2-back working memory test for the number of activated voxels (that differ significantly from reference wave form) in Anterior Cingulate Cortex (ACC). A responder in the 2-back working memory test was defined as a patient showing a response latency of less than 713 ms at endpoint. This is based on baseline data from the matched control population in a functional imaging study in patients with obstructive sleep apnea. The change from Baseline to Endpoint in the number of activated voxels for each treatment group among the responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=8 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=4 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the ACC on fMRI by 2-Back Working Memory Test -Change From Baseline; Subgroup-Responders in 2 Back Memory Test	-38.6 Voxels Standard Error 113.68	-227.8 Voxels Standard Error 213.46

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group Analysis of subjects who were responders on the 2-Back Working Memory Test (had a response latency \< 713 ms) at Endpoint

This is a subgroup analysis of responders on the 2-back working memory test for the number of voxels (voxels that differ significantly from reference wave form) in Posterior Parietal Cortex (PPC). A responder in the 2-back working memory test was defined as a patient showing a response latency of less than 713 ms at endpoint. This is based on baseline data from the matched control population in a functional imaging study in patients with obstructive sleep apnea. The change from Baseline to Endpoint in the number of activated voxels for each treatment group among the responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=8 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=4 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the PPC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Responders in 2 Back Memory Test	-789.1 Voxels Standard Error 588.22	-397.7 Voxels Standard Error 366.33

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group Analysis of subjects who were responders on the 2-Back Working Memory Test (response latency \< 713 ms) at Endpoint

This is a subgroup analysis of responders on the 2-back working memory test for the number of activated voxels (voxels that differ significantly from reference wave form) in the thalamus. A responder in the 2-back working memory test was defined as a patient showing a response latency of less than 713 ms at endpoint. This is based on baseline data from the matched control population in a functional imaging study in patients with obstructive sleep apnea. The change from Baseline to Endpoint in the number of activated voxels for each treatment group among the responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=8 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=4 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the Thalamus on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Responders in 2 Back Memory Test	-764.7 Voxels Standard Error 626.55	-1446.7 Voxels Standard Error 1091.13

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group analysis among non-responders on the 2-Back Working Memory Test (response latency of 713 ms or greater) at Endpoint

This is a subgroup analysis of non-responders on the 2-back working memory test for the number of voxels meeting the predefined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI). A non-responder in the 2-back working memory test was defined as a patient showing a response latency of 713 ms or greater at endpoint. The change from Baseline to Endpoint in the number of activated voxels in the dorsolateral prefrontal cortex (DLPFC)for each treatment group among the non-responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=12 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=12 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the DLPFC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test	-2279.4 Voxels Standard Error 686.69	-2784.4 Voxels Standard Error 1643.79

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group analysis of non-responders on the 2-Back Working Memory Test (response latency of 713 ms or greater) at Endpoint

This is a subgroup analysis of non-responders on the 2-back working memory test for the number of voxels meeting the predefined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI). A non-responder in the 2-back working memory test was defined as a patient showing a response latency of 713 ms or greater at endpoint. The change from Baseline to Endpoint in the number of activated voxels in the anterior cingulate cortex (ACC)for each treatment group among the non-responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=12 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=12 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the ACC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test	-153.1 Voxels Standard Error 116.30	-199.4 Voxels Standard Error 94.97

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group analysis of non-responders on the 2-Back Working Memory Test (response latency of 713 ms or greater) at Endpoint

This is a subgroup analysis of non-responders on the 2-back working memory test for the number of voxels meeting the predefined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI). A non-responder in the 2-back working memory test was defined as a patient showing a response latency of 713 ms or greater at endpoint. The change from Baseline to Endpoint in the number of activated voxels in the posterior parietal cortex (PPC)for each treatment group among the non-responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=12 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=12 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the PPC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test	-465.5 Voxels Standard Error 273.77	-898.5 Voxels Standard Error 554.98

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Sub-group analysis of non-responders on the 2-Back Working Memory Test (response latency of 713 ms or greater) at Endpoint

This is a subgroup analysis of non-responders on the 2-back working memory test for the number of voxels meeting the predefined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI). A non-responder in the 2-back working memory test was defined as a patient showing a response latency of 713 ms or greater at endpoint. The change from Baseline to Endpoint in the number of activated voxels in the thalamus for each treatment group among the non-responders is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=12 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=12 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Number of Contiguous Activated Voxels Meeting Predefined Threshold in the Thalamus on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test	-893.1 Voxels Standard Error 545.48	-1408.3 Voxels Standard Error 795.57

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one observation after baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the blood oxygen level dependent (BOLD) signal intensity in the dorsolateral prefrontal cortex (DLPFC).

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the BOLD Signal Intensity in the Dorsolateral Prefrontal Cortex (DLPFC) at Resting State	5.556 BOLD signal intensity Full Range 57.6441 • Interval -40.0 to 971.429	3.755 BOLD signal intensity Full Range 5.0906 • Interval -39.855 to 33.333

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after Baseline)

Population: Full Analysis Set defined as subjects who had at least one observation after baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the blood oxygen level dependent signal (BOLD) intensity in the anterior cingulate cortex (ACC).

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the BOLD Signal Intensity in the Anterior Cingulate Cortex (ACC) at Resting State	2.778 BOLD signal intensity Full Range 9.6476 • Interval -100.0 to 85.714	0.0 BOLD signal intensity Full Range 7.2850 • Interval -45.714 to 75.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who have had at least one observation after Baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the blood oxygen level dependent (BOLD) signal intensity in the posterior parietal cortex (PPC).

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline in the BOLD Signal Intensity in the Posterior Parietal Cortex (PPC) at Resting State	2.667 BOLD signal intensity Full Range 8.9840 • Interval -25.0 to 144.444	2.479 BOLD signal intensity Full Range 3.3927 • Interval -32.283 to 18.831

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after Baseline)

Population: Full Analysis Set defined as subjects who have had at least one observation after Baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the blood oxygen level dependent (BOLD) signal intensity in the thalamus.

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the BOLD Signal Intensity in the Thalamus at Resting State	5.128 BOLD signal intensity Full Range 32.2812 • Interval -30.769 to 544.444	1.429 BOLD signal intensity Full Range 3.9156 • Interval -29.204 to 22.222

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects who had at least one observation after Baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the number of contiguous activated voxels (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI) in the dorsolateral prefrontal cortex.

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in the Dorsolateral Prefrontal Cortex (DLPFC) at Resting State	941.5 Voxels Full Range 1613.73 • Interval -12443.0 to 11600.0	-174.5 Voxels Full Range 1418.92 • Interval -9388.5 to 12014.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after Baseline)

Population: Full Analysis Set defined as subjects with at least one observation after Baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the number of contiguous activated voxels meeting pre-defined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI) in the anterior cingulate cortex (ACC).

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in Anterior Cingulate Cortex (ACC) at Resting State	-27.5 Voxels Full Range 197.41 • Interval -1969.0 to 1229.5	-54.0 Voxels Full Range 231.69 • Interval -883.0 to 2750.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after Baseline)

Population: Full Analysis Set defined as subjects with at least one observation after Baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the number of activated voxels meeting predefined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI) in the posterior parietal cortex (PPC).

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in Posterior Parietal Cortex (PPC) at Resting State	22.0 Voxels Full Range 517.56 • Interval -4602.0 to 759.0	104.3 Voxels Full Range 382.49 • Interval -1994.5 to 1747.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after baseline)

Population: Full Analysis Set defined as subjects with at least one observation after Baseline

At resting state, this is an analysis of the change from Baseline to Endpoint in the number of activated voxels meeting predefined threshold (voxels that differ significantly from reference wave form) on functional magnetic resonance imaging (fMRI) in the thalamus.

Outcome measures

Outcome measures
Measure	Armodafinil n=17 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=16 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in the Thalamus at Resting State	-621.0 Voxels Full Range 517.64 • Interval -5251.0 to 3171.5	-883.8 Voxels Full Range 689.30 • Interval -5876.0 to 5806.0

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 2 or last observation after Baseline)

Population: Full Analysis Set defined as subjects who had at least one observation after Baseline

During anatomic scanning (and prior to functional runs when anatomic scanning was not performed), a modified continuous 10 minute attention task ("Psychomotor Vigilance Test \[PVT\]-like task," nearly identical to the PVT but for absence of performance feedback) was run to obtain a measure of vigilance in the scanner-in this instance, the "+" symbol appeared at random (mean inter trial interval of 5 seconds, range 2 - 10 seconds) but disappeared when subject pressed a button. Subject performance speed was measured. Change in subject performance speed from Baseline to Endpoint is presented.

Outcome measures

Outcome measures
Measure	Armodafinil n=15 Participants Armodafinil was provided to patients in bottles of sixty 50 mg tablets. Patients took a 50 mg dose on Day 1, which was increased by 50 mg on Days 2, 5, and 8 to a total dose of 200 mg per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.	Placebo n=15 Participants Placebo tablets matching the 50 mg armodafinil tablets were provided by Cephalon to patients in bottles of sixty tablets. Patients took a single tablet on Day 1, which was increased by 1 tablet on Days 2, 5, and 8 to a total dose of 4 tablets per day. This was taken as a once daily dose at or before 8 AM, approximately 30 minutes before breakfast.
Change From Baseline to Endpoint (2 Weeks or Last Observation After Baseline) in the Mean Response Latency in the Psychomotor Vigilance-Like Test	-31.9 milliseconds (ms) Standard Error 13.41	-6.8 milliseconds (ms) Standard Error 13.16

Adverse Events

Armodafinil (200 mg/Day)

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Armodafinil (200 mg/Day) n=21 participants at risk Armodafinil was titrated during the double-blind treatment period starting with 50 mg/day (1 tablet) on Day 1, increasing to 100 mg/day (2 tablets) on day 2, 150 mg/day (3 tablets) on day 5, and 200 mg/day (4 tablets) on day 8, which was continued for the remainder of the 2-week double-blind treatment period.	Placebo n=19 participants at risk Placebo tablets matching the armodafinil tablets were titrated during the double-blind treatment period starting with 1 tablet/day on Day 1, increasing to 2 tablets/day on day 2, 3 tablets/day on day 5, and 4 tablets/day on day 8, which was continued for the remainder of the 2-week double-blind treatment period.
Gastrointestinal disorders Abdominal Pain upper	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Cardiac disorders Angina pectoris	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Psychiatric disorders Anxiety	0.00% 0/21 • 2 Weeks	5.3% 1/19 • 2 Weeks
Psychiatric disorders Bruxism	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Investigations Cardiac murmur	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
General disorders Chest discomfort	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Respiratory, thoracic and mediastinal disorders Cough	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Gastrointestinal disorders Diarrhea	9.5% 2/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Nervous system disorders Dizziness	0.00% 0/21 • 2 Weeks	5.3% 1/19 • 2 Weeks
General disorders Energy increased	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Nervous system disorders Headache	19.0% 4/21 • 2 Weeks	5.3% 1/19 • 2 Weeks
Investigations Heart rate increased	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Nervous system disorders Hypoaesthesia	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
General disorders Irritability	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Infections and infestations Nasopharyngitis	14.3% 3/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Gastrointestinal disorders Nausea	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Renal and urinary disorders Pollakuria	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Immune system disorders Seasonal allergy	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Nervous system disorders Sensory disturbance	0.00% 0/21 • 2 Weeks	5.3% 1/19 • 2 Weeks
Cardiac disorders Tachycardia	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Infections and infestations Upper respiratory tract infection	4.8% 1/21 • 2 Weeks	0.00% 0/19 • 2 Weeks
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/21 • 2 Weeks	5.3% 1/19 • 2 Weeks
Eye disorders Visual impairment	0.00% 0/21 • 2 Weeks	5.3% 1/19 • 2 Weeks

Additional Information

Sponsor's Medical Expert, Clinical Research

Cephalon, Inc.

Phone: 1-800-896-5855

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER