The MSLT is an objective assessment of sleepiness that measures the likelihood of falling asleep. Four 20-minute (maximum) MSLT naps were performed at 0900, 1100, 1300, and 1500. The participant, dressed in nonconstricting clothes, was instructed to lie quietly and attempt sleep. Each MSLT nap continued until: (a) 3 consecutive 30-second epochs of stage 1 sleep were reached or (b) any single, 30-second epoch of stage 2, 3, 4, or rapid eye movement (REM) sleep was reached. Sleep latency for each nap and average sleep latency for the 4 naps were tabulated. According to clinical protocol for the MSLT, each nap was terminated after 20 minutes if no sleep occurred. If a participant did not fall asleep in 20 minutes, his/her sleep latency for that nap was set to 20 minutes. Sleep latency was measured as the elapsed time from lights-out to the first epoch scored as sleep. With a 30-second scoring epoch, this criterion was reached when sleep occupied at least 16 seconds of any epoch.

Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with measurements at given time point.

The CGI-C is the clinician's rating of disease severity as compared with pretreatment, assessed by the Clinical Global Impression of Severity (CGI-S). Severity of illness, as related to excessive sleepiness, was assessed at baseline by the CGI-S, which consists of 7 categories: normal-shows no sign of illness, borderline ill, mildly (slightly) ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. The clinician assessed the change from baseline in the participant's condition, as related to excessive sleepiness, in response to treatment. The CGI-C uses 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 were defined as those participants who were considered much or very much improved on the CGI-C. Those in all other categories of the CGI-C were considered nonresponders.

Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment).

The MSLT is an objective assessment of sleepiness that measures the likelihood of falling asleep. Four 20-minute (maximum) MSLT naps were performed at 0900, 1100, 1300, and 1500. The participant, dressed in nonconstricting clothes, was instructed to lie quietly and attempt sleep. Each MSLT nap continued until: (a) 3 consecutive 30-second epochs of stage 1 sleep were reached or (b) any single, 30-second epoch of stage 2, 3, 4, or rapid eye movement (REM) sleep was reached. Sleep latency for each nap and average sleep latency for the 4 naps were tabulated. According to clinical protocol for the MSLT, each nap was terminated after 20 minutes if no sleep occurred. Sleep latency was measured as the elapsed time from lights-out to the first epoch scored as sleep. With a 30-second scoring epoch, this criterion was reached when sleep occupied at least 16 seconds of any epoch.

Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with data at given time points.

The CGI-C is the clinician's rating of disease severity as compared with pretreatment, assessed by the Clinical Global Impression of Severity (CGI-S). Severity of illness, as related to excessive sleepiness, was assessed at baseline by the CGI-S, which consists of 7 categories: normal-shows no sign of illness, borderline ill, mildly (slightly) ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. The clinician assessed the change from baseline in the participant's condition, as related to excessive sleepiness, in response to treatment. The CGI-C uses 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 were defined as those participants who were considered much or very much improved on the CGI-C. Those in all other categories of the CGI-C were considered nonresponders.

Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with a nonmissing value at given time point.

The TBI-WIS is a validated participant-rated instrument for assessing a participant's functional ability after TBI and the functional demands of their job. The assessment consists of 36 questions to which the participant responded with a "true" or "not true" answer. To score the questionnaire, the number of "true" responses is counted: if < 2, the risk is low; 2 to 23, the risk is medium; and >23, the risk is high, for work instability. Score range is 0 (lowest risk for work instability) to 36 (highest risk for work instability).

Participants in the Full Analysis Set (participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment) with a baseline TBI-WIS measurement; n=number of participants with values at given time points.

The patient's evaluation of excessive daytime sleepiness was measured by the ESS. The ESS score is based on responses to questions referring to 8 everyday situations (eg, sitting and reading, talking to someone, being stopped in traffic) and reflects a patient's propensity to fall asleep in those situations. The ESS score is derived from the sum of the values from questions corresponding to the 8 situations. Scores for the ESS range from 0 to 24, with a higher score indicating a greater daytime sleepiness. This test was self-administered.

Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with data at given time point.

The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors since last visit (SLV). The number of participants answering 'no' to all 9 yes/no questions about suicidal behaviors, ideations, and acts are presented. Questions included the presence of the following: a wish to be dead; nonspecific active suicidal thoughts; actual suicide attempt; non-suicidal self-injurious behavior; interrupted attempt; aborted attempt; suicidal behavior; preparatory suicidal acts or behavior; and completed suicide.

Safety analysis set (all participants who received 1 or more doses of study drug); n=all participants with a nonmissing value at given time point.

The self-reported S-HAM-D6 is a validated scale developed from the core depressive items of the 17 Item Hamilton Depression Inventory (HAM-D17). The HAM-D6 (Items 1, 2, 7, 8, 10, 13 from the 17-item HAMD) evaluates "core" symptoms of Major Depressive Disorder (MDD). The assessment consists of 6 items representing depressed mood, guilt, work and activities, retardation, psychic anxiety, and general somatic symptoms. Each item is evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). Total scores range from 0 (normal) to 22 (severe). Scores greater than 12 indicate moderate to severe depression and scores less than 12 indicate mild depression.

Participants in the Safety Analysis Set (participants who received 1 or more doses of study drug) with a baseline S-HAM-D6 measurement; n=number of participants with nonmissing data at given time point.

NPSG continuously records normal and abnormal physiological activity during an entire night. It documents the adequacy of sleep, including the frequency, duration, and total amounts of stage 1-2, stage 3-4 (slow wave sleep), and rapid eye movement (REM) sleep.

Safety Analysis Set (all participants who received 1 or more doses of study drug); n=number of participants with data at given time point.

To evaluate the impact of treatment with armodafinil on the pharmacokinetics of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) (as appropriate), plasma concentrations at weeks 4, 8, and 12 (or last postbaseline observation) were to be assessed.

Due to the limited samples available for measurement of concentrations of antidepressants in the study, the plasma concentrations of antidepressants were not measured. The planned pharmacokinetic evaluation of the impact of armodafinil treatment on the pharmacokinetics of selective antidepressants was not conducted.

Therapeutic classification of concomitant medications used by ≥5% of participants throughout the study. Participants are counted only once in each therapeutic class category. Medications were included in the table if the proportion of participants in the combined armodafinil treatment group was ≥5%.

All randomized participants

AE=any untoward medical occurrence in a patient that develops or worsens in severity during the conduct of the clinical study of a pharmaceutical product and does not necessarily have a causal relationship to the study drug. SAE=any AE that resulted in any of the following: death; a life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly or birth defect; an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-related AEs=definite, probable, possible, or missing relationship. Protocol-defined AEs=treatment-emergent adverse events associated with skin rash, hypersensitivity reaction, emergent suicidal ideation or suicide attempt, depression, psychosis (including hypomanic or manic episode), and seizure or suspected seizure were considered to be of potential clinical importance.

Safety Analysis Set (all participants who received 1 or more doses of study drug).

Normal ranges for serum chemistry values: blood urea nitrogen (BUN), 1.43 - 8.57 mmol/L; uric acid, 124.91 - 493.68 μmol/L; aspartate aminotransferase (AST), 11 - 36 U/L; gamma-glutamyl transpeptidase (GGT), 10 - 61 U/L; total bilirubin, 3.42 - 20.52 μmol/L.

Participants in the Safety Analysis Set with a baseline and postbaseline measurement.

Normal ranges for hematology values: white blood cell (WBC) count, 3.8 - 10.7 x 10^9/L; absolute neutrophil count (ANC), 1.96 - 7.23 x 10^9/L. Participants may have had more than one clinically significant abnormal value.

Participants in the Safety Analysis Set with a baseline and postbaseline measurement.

Participants with at least one clinically significant postbaseline urinalysis abnormality, specifically presented is blood (hemoglobin) in urine >=2 units increase from baseline.

Participants in the Safety Analysis Set with a baseline and postbaseline measurement.

Criteria for clinically significant abnormal vital signs values: heart rate, ≤50 beats per minute (bpm) and decrease from baseline of ≥15 bpm; sitting systolic blood pressure, ≤90 mm Hg and decrease from baseline of ≥20 mm Hg; sitting diastolic blood pressure, ≤50 mm Hg and decrease from baseline of ≥15 mm Hg.

Participants in the Safety Analysis Set with a baseline and postbaseline measurement.

Criteria for World Health Organization (WHO) notable blood pressure (BP) values: systolic blood pressure, ≥140 mm Hg plus increase of ≥10% from baseline; diastolic blood pressure, ≥90 mm Hg plus increase of ≥10% from baseline.

Participants in the Safety Analysis Set with a baseline and postbaseline measurement.

Number of participants with shifts from normal/abnormal 12-lead ECG findings at baseline (BL) to (→) normal/abnormal findings overall are presented. For overall, the worst postbaseline finding (the abnormal finding if there are both normal and abnormal findings) for the participant between baseline and endpoint (defined as last postbaseline observation, up to Week 12) is summarized. Shifts (normal and abnormal) from baseline to overall are summarized using participant counts. Any ECG finding that was judged by the investigator as a clinically meaningful change (worsening) compared to baseline was recorded as an adverse event.

Participants in the Safety Analysis Set with a baseline and postbaseline measurement are summarized.

Number of participants with shifts from normal/abnormal physical examination findings at baseline (BL) to (→) normal/abnormal findings at endpoint (EP, defined as last postbaseline observation, up to Week 12). Shifts (normal and abnormal) from baseline to endpoint are summarized using participant counts for each physical examination category. A newly diagnosed finding was defined as being normal or missing at baseline and abnormal at least once during the study. Any physical examination finding that was judged by the investigator as a clinically significant change (worsening) compared to a baseline value was considered an adverse event. HEENT=head, eyes, ears, nose, throat.

For each category, only participants in the Safety Analysis Set with a baseline and postbaseline measurement are summarized.