Study to Evaluate the Efficacy and Safety of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury

Inclusion Criteria:

• The patient had a mild (Glasgow Coma Scale [GCS] score 13-15) or moderate (GCS score 9-12) closed TBI at the time of the injury, and the injury occurred 1 to 10 yearsprior to screening.
• The patient had a Glasgow Outcome Scale score of 5 at the screening visit.
• The patient had an Epworth Sleepiness Scale (ESS) score of at least 10 at screening.
• The patient had a mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of 4 naps) of less than 8 minutes at baseline.
• The patient had a Clinical Global Impression of Severity of Illness (CGI-S) ratingrelating to their excessive sleepiness of 4 or more at the screening and baselinevisits.
• The patient had a complaint of excessive sleepiness (at least 5 days/week on average)for at least 3 months, and the excessive sleepiness began within 12 months of the TBI.
• Written informed consent was obtained.
• The patient was a man or woman of any ethnic origin 18 to 65 years of age.
• If admitted to an inpatient treatment facility, the patient was discharged at least 1month prior to the screening visit.
• The patient did not have any medical or psychiatric disorders that could account forthe excessive sleepiness.
• Women of childbearing potential (not surgically sterile or 2 years postmenopausal),used a medically accepted method of contraception, and continued use of one of thesemethods for the duration of the study (and for 30 days after participation in thestudy). Acceptable methods of contraception included: abstinence, barrier method withspermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) inconjunction with a barrier method, or intrauterine device (IUD).
• The patient was in otherwise good health, as judged by the investigator, on the basisof a medical and psychiatric history, physical examination, electrocardiogram (ECG),serum chemistry, hematology, and urinalysis.
• The patient was willing and able to comply with study restrictions and to attendregularly scheduled clinic visits as specified in this protocol.
• The patient had a Mini Mental State Examination (MMSE) score of more than 26 at thescreening visit.
• The patient was on stable dosages of medications (allowed by the protocol) for aminimum of 3 months (selective serotonin reuptake inhibitors [SSRIs] andserotonin-norepinephrine reuptake inhibitors [SNRIs]), 8 weeks (contraceptives), or 4weeks (all other allowed medication) before the screening visit and was not likely torequire a change in therapy for at least 12 weeks on the basis of the investigators'assessment.
• The patient had a habitual bedtime between 2100 and 2400.
• The patient had no other head injuries that, based on medical record documentation orhistory from the patient and reliable informant (if available), were temporallyrelated to the onset or to any worsening of excessive sleepiness.
• The patient had no other head injury fulfilling the criteria for TBI within ±1 year ofthe TBI identified according to criterion (a1).

Exclusion Criteria:

• The patient had a history of 2 or more episodes of transient loss of consciousness (LOC) without clear medical explanation, or had a history of known or suspected pseudoseizure (psychogenic seizure). Patients with a history of seizure or epilepsy may havebeen eligible following discussion with the medical monitor.
• The patient required, or was likely to require, treatment with anticonvulsantmedication during the study, or had taken anticonvulsant medication within 6 monthsbefore the screening visit.
• The patient had an unstable or uncontrolled medical (including illnesses related tothe cardiovascular [including patients with a history of left ventricular hypertrophyor in patients with mitral valve prolapse who had experienced the mitral valveprolapse syndrome], renal, or hepatic systems or surgical) condition (treated oruntreated) or was not a suitable candidate for treatment with armodafinil, as judgedby the investigator.
• The patient had neurosurgery involving the brain or brainstem.
• The patient had a history of schizophrenia, bipolar disorder, psychotic depression, orother psychotic episode.
• The patient had any current Axis I disorder (including depression and posttraumaticstress disorder [PTSD]), as assessed by Structured Clinical Interview for Diagnosticand Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID). Thepatient had any Axis II disorder (as assessed by SCID) that, in the opinion of theinvestigator, would affect patient participation in the study or full compliance withstudy procedures.
• The patient had a history of, or currently met The International Classification ofSleep Disorders, Edition 2 (ICSD 2) (American Academy of Sleep Medicine 2005) criteriafor narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), shift work sleepdisorder (SWSD), or any other sleep disorder associated with excessive daytimesleepiness; or the patient had a history of idiopathic hypersomnia, insomnia (requiring treatment), or sleep disorder before the development of the TBI.
• The patient had 85% or less sleep efficiency (sleep duration ÷ time in bed x 100%) asdetermined from nocturnal polysomnography (NPSG).
• The patient had any disorder that may interfere with drug absorption, distribution,metabolism, or excretion.
• The patient used any medications, including over-the-counter (OTC) medicinesdisallowed by the protocol, within 7 days or 5 half lives (medication or its activemetabolites), whichever was longer, before the screening visit.
• The patient had a need for chronic pain medications.
• In the judgment of the investigator, the patient had a clinically significantdeviation from normal in the physical examination.
• In the judgment of the investigator, the patient had any clinically significant ECGfinding.
• The patient had a diagnosis of any type of dementia.
• The patient had a history of suicidal ideation (considered by the investigator to beof current clinical significance), or was currently suicidal.
• The patient had a known hypersensitivity to armodafinil, racemic modafinil, or anycomponent of the study drug tablets. Armodafinil tablets contain the followinginactive ingredients: croscarmellose sodium, lactose, magnesium stearate,microcrystalline cellulose, povidone, and pregelatinized starch.
• The patient had a history of any clinically significant cutaneous drug reaction, or ahistory of clinically significant hypersensitivity reaction, including multipleallergies or drug reactions.
• The patient had a clinical laboratory test value(s) outside the range(s) specified byprotocol (or any other clinically significant laboratory abnormality), and the medicalmonitor had not provided written approval for study participation.
• The patient had a history (within the past 5 years) of alcohol, narcotic, or any otherdrug abuse (with the exception of nicotine) as defined by the Diagnostic andStatistical Manual of Mental Disorders of the American Psychiatric Association, 4thEdition, Text Revision (DSM-IV-TR), or the patient had current evidence of substanceuse, without medical explanation, confirmed by results of a urine drug screen (UDS).
• The patient had taken armodafinil, modafinil or other stimulant medication forexcessive sleepiness within 1 month of the screening visit.
• The patient was a pregnant or lactating woman. (Any women becoming pregnant during thestudy were to be withdrawn from the study.)
• The patient was known to have tested positive for human immunodeficiency virus (HIV).
• The patient consumed an average of more than 600 mg of caffeine per day, includingcoffee, tea and/or other caffeine-containing beverages or food.
• The patient used any investigational drug within 1 month before the screening visit.
• The patient was receiving workmen's compensation or was in active litigation withregard to TBI.
• The patient had a self-reported Hamilton Depression Rating Scale, 6 Item Version (SHAM D6) score of more than 4 at the screening visit.