title: Armodafinil for the treatment of excessive sleepiness associated with mild or moderate closed traumatic brain injury: a 12-week, randomized, double-blind study followed by a 12-month open-label extension.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of armodafinil in patients with excessive sleepiness following mild or moderate closed traumatic brain injury (TBI).
  
  
  METHODS
  Randomized, placebo-controlled, double-blind trial followed by open-label extension.
  
  
  METHODS
  40 US centers.
  
  
  METHODS
  Adults with closed TBI (N = 117), Glasgow Coma Scale score >8 at time of injury; baseline Epworth Sleepiness Scale (ESS) ≥10; sleep latency <8 minutes on multiple sleep latency test (MSLT); and Clinical Global Impression-Severity of Illness (CGI-S) score ≥4 for excessive sleepiness.
  
  
  METHODS
  Patients received armodafinil (50, 150, or 250 mg/day) or placebo for 12 weeks followed by an optional 12-month open-label extension.
  
  
  RESULTS
  Outcomes included MSLT, ESS, Clinical Global Impression-Change (CGI-C), TBI-Work Instability Scale (TBI-WIS), CGI-S, and tolerability. The study was terminated early due to low enrollment. Patients receiving 250 mg armodafinil showed significant improvement in sleep latency from baseline to final visit versus placebo (+7.2 minutes vs. +2.4 minutes; p = 0.0010). CGI-C ratings were much/ very much improved in approximately 50% of patients receiving 150 and 250 mg armodafinil, compared to 38% on placebo. ESS and TBI-WIS scores were not significantly different between groups. In the open-label extension (N = 49), patients demonstrated gradual improvement in ESS, TBI-WIS, and CGI-S scores up to 48 weeks post-baseline. Armodafinil was generally well tolerated, with headache the most common adverse event in both double-blind and open-label portions.
  
  
  CONCLUSIONS
  Armodafinil 250 mg significantly improved sleep latency in patients with excessive sleepiness associated with mild or moderate TBI. Efficacy and tolerability of armodafinil were sustained throughout the open-label extension.
  
  
  BACKGROUND
  NCT00893789, NCT00983437.
authors.affiliation: Pacific Sleep Medicine Services, Palm Springs, CA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Menn
authors.affiliation: Teva Pharmaceutical Industries Ltd., Frazer, PA.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.affiliation: Sleep Disorders Center of Georgia, Atlanta, GA.
authors.forename: Alan
authors.initials: A
authors.lastname: Lankford
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001930:Brain Injuries / Q000150:complications* / Q000175:diagnosis; D016001:Confidence Intervals; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale; D016489:Head Injuries, Closed / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D017286:Polysomnography; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D000077408:Modafinil
keywords: armodafinil; excessive sleepiness; traumatic brain injury