Study to Evaluate the Safety, Tolerability, and Efficacy of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Sleepiness; Wounds and Injuries
Intervention: Armodafinil
Intervention MeSH terms: Modafinil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the safety and tolerability of long-term
      (12 months) armodafinil treatment in patients with excessive sleepiness associated with mild
      or moderate closed traumatic brain injury (TBI).
    

Eligibility criteria:

        Patients enrolled in this study will be rollover patients (those who completed the previous
        double-blind efficacy study C10953/3067/ES/MN) and new patients (those who did not
        participate in the C10953/3067/ES/MN study).

        Inclusion Criteria (for New Patients):

          -  The patient has a mild (Glasgow Coma Scale [GCS] score = 13-15) or moderate (GCS score
             = 9-12) closed traumatic brain injury (TBI) at the time of the injury, and the injury
             occurred 1 to 10 years prior to screening.

          -  The patient has a Glasgow Outcome Scale score of 5.

          -  The patient has an Epworth Sleepiness Scale (ESS) score of at least 10.

          -  The patient has a mean sleep latency on the Multiple Sleep Latency Test (MSLT)
             (average of 4 naps) of less than 8 minutes.

          -  The patient has a Clinical Global Impression of Severity of Illness (CGI-S) rating
             relating to their excessive sleepiness of 4 or more.

          -  The patient has 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
             identified according to the first inclusion criterion.

          -  Written informed consent was obtained.

          -  If admitted to an in-patient treatment facility, the patient was discharged at least 1
             month prior to the screening visit.

          -  The patient does not have any medical or psychiatric disorders that could account for
             the excessive sleepiness.

          -  Women of childbearing potential (not surgically sterile or 2 years postmenopausal),
             used a medically accepted method of contraception, and continued use of 1 of those
             methods for the duration of the study (and for 30 days after participation in the
             study).

          -  The patient is in otherwise good health, as judged by the investigator, on the basis
             of a medical and psychiatric history, physical examination, electrocardiogram (ECG),
             serum chemistry, hematology, and urinalysis.

          -  The patient is willing and able to comply with study restrictions and attend regularly
             scheduled clinic visits as specified in the protocol.

          -  The patient has an mini-mental state examination (MMSE) score of more than 26 at the
             screening visit.

          -  The patient was on stable dosages of medications (allowed by the protocol) for a
             minimum of 3 months (selective serotonin reuptake inhibitor [SSRIs] and serotonin and
             norepinephrine reuptake inhibitor [SNRIs]), 8 weeks (contraceptives), or 4 weeks (all
             other allowed medication) before the screening visit and is not likely to require a
             change in therapy for at least 12 weeks on the basis of the investigators' assessment.

          -  The patient has no other head injuries that, based on medical record documentation or
             history from the patient and reliable informant (if available), were temporally
             related to the onset or to any worsening of excessive sleepiness.

          -  The patient has no other head injury fulfilling the criteria for TBI within ±1 year of
             the TBI identified according to the first inclusion criterion.

          -  The patient has a habitual bedtime between 2100 and 2400.

        Inclusion Criteria (for Rollover Patients from Study C10953/3067/ES/MN):

          -  The patient has completed 12 weeks of double-blind treatment in Study
             C10953/3067/ES/MN.

          -  Written informed consent was obtained.

          -  Women of childbearing potential (not surgically sterile or 2 years postmenopausal),
             used a medically accepted method of contraception and agreed to continue use 1 of
             those methods for the duration of the study and for 30 days after participation in the
             study.

          -  The patient is in otherwise good health, as judged by the investigator, on the basis
             of a medical and psychiatric history, physical examination, ECG, serum chemistry,
             hematology, and urinalysis.

          -  The patient is willing and able to comply with study restrictions and to remain at the
             clinic for the required duration during the study period, and was willing to return to
             the clinic for the follow-up evaluation as specified in the protocol.

        Exclusion Criteria (for New Patients):

          -  The patient has a history of 2 or more episodes of transient loss of consciousness
             without clear medical explanation, or has a history of known or suspected pseudo
             seizure (psychogenic seizure). Patients with a history of seizure or epilepsy may be
             eligible following discussion with the medical monitor.

          -  The patient requires, or is likely to require, treatment with anticonvulsant
             medication during the study; or has taken anticonvulsant medication within 6 months
             before the screening visit.

          -  The patient has an unstable or uncontrolled medical (including illnesses related to
             the cardiovascular, renal, or hepatic systems) or surgical condition (treated or
             untreated) or was not a suitable candidate for treatment with armodafinil, as judged
             by the investigator.

          -  The patient has had neurosurgery involving the brain or brainstem.

          -  The patient has a history of schizophrenia, bipolar disorder, psychotic depression, or
             other psychotic episode.

          -  The patient has any current Axis I disorder (including depression and posttraumatic
             stress disorder [PTSD]), as assessed by Structured Clinical Interview for Diagnostic
             and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID).
             Patients with any Axis II disorder, that in the opinion of the investigator, would
             affect patient participation in the study or full compliance with study procedures.

          -  The patient has a history of, or currently meets The International Classification of
             Sleep Disorders, Edition 2 (ICSD-2) criteria for any other sleep disorder associated
             with excessive daytime sleepiness; or the patient has a history of idiopathic
             hypersomnia, insomnia (requiring treatment), or sleep disorder before the development
             of the TBI.

          -  The patient has 85% or less sleep efficiency (sleep duration ÷ time in bed x 100%) as
             determined from Nocturnal Polysomnography (NPSG).

          -  The patient has any disorder that may have interfered with drug absorption,
             distribution, metabolism, or excretion.

          -  The patient has used any medications including over-the-counter (OTC) medicines
             disallowed by the protocol within 7 days or 5 half-lives (medication or its active
             metabolites), whichever is longer.

          -  The patient has a need for chronic pain medications.

          -  In the judgment of the investigator, the patient has a clinically significant
             deviation from normal in the physical examination.

          -  In the judgment of the investigator, the patient has any clinically significant ECG
             finding.

          -  The patient has a diagnosis of any type of dementia.

          -  The patient has a history of suicidal ideation (considered by the investigator to be
             of clinical significance), or is suicidal.

          -  The patient has a known hypersensitivity to armodafinil, racemic modafinil, or any
             component of the study drug tablets. Armodafinil tablets contained the following
             inactive ingredients: croscarmellose sodium, lactose, magnesium stearate,
             microcrystalline cellulose, povidone, and pregelatinized starch.

          -  The patient has a history of any clinically significant cutaneous drug reaction, or a
             history of clinically significant hypersensitivity reaction, including multiple
             allergies or drug reactions.

          -  The patient has a clinical laboratory test value(s) outside the range(s) specified in
             the protocol (or any other clinically significant laboratory abnormality), and the
             medical monitor had not provided written approval for study participation.

          -  The subject has a history (within the past 5 years) of alcohol, narcotic, or any other
             drug abuse (with the exception of nicotine) as defined by the Diagnostic and
             Statistical Manual of Mental Disorders of the American Psychiatric Association, 4th
             Edition (DSM-IV-TR) or the patient had current evidence of substance use, without
             medical explanation, confirmed by results of a urine drug screen (UDS).

          -  The patient has taken armodafinil, modafinil, or other stimulant medication for
             excessive sleepiness within 1 month of the screening visit.

          -  The patient is a pregnant or lactating woman.

          -  The patient is known to have tested positive for human immunodeficiency virus (HIV).

          -  The patient consumes an average of more than 600 mg of caffeine per day, including
             coffee, tea and/or other caffeine-containing beverages or food.

          -  The patient has used any investigational drug within 1 month before the screening
             visit.

          -  The patient is receiving workmen's compensation or was in active litigation with
             regard to TBI.

          -  The patient has a Self-Reported Hamilton Depression Rating Scale, 6 Item Version
             (S-HAM-D6) score of more than 4.

        Exclusion Criteria (for Rollover Patients from Study C10953/3067/ES/MN):

          -  The patient has any clinically significant unstable or uncontrolled medical, surgical,
             or psychiatric conditions (treated or untreated) or may not be a suitable candidate
             for treatment with armodafinil, as judged by the investigator or medical monitor.

          -  The patient has current evidence of active psychosis, including stimulant-induced
             psychosis or mania.

          -  The patient has current evidence of non-medical substance use confirmed by results of
             a UDS.

          -  The patient has used any medications including OTC medicines disallowed by the
             protocol (except armodafinil use in study 3067) within 7 days or 5 half-lives of the
             drug and its active metabolites, whichever is longer.

          -  The patient has a clinically significant deviation from normal in the physical
             examination as judged by the investigator.

          -  The patient has a clinically significant laboratory abnormality, as judged by the
             investigator, without prior written approval by the medical monitor.

          -  The patient has hypersensitivity to armodafinil or modafinil, or any of the excipients
             of either.

          -  The patient is a pregnant or lactating woman.

          -  The patient is unlikely to comply with the study protocol, or is unsuitable for any
             other reason, as judged by the investigator.

          -  The patient consumes an average of more than 600 mg of caffeine per day (approximately
             equivalent to 5 or more cups of coffee), including coffee, tea, and/or other
             caffeine-containing beverages or food.