Armodafi nil 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 effi cacy and tolerability of armodafi nil in patients with excessive sleepiness following mild or moderate closed traumatic brain injury (TBI). Design: Randomized, placebo-controlled, double-blind trial followed by open-label extension. Setting: 40 US centers. Patients: 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. Intervention: Patients received armodafi nil (50, 150, or 250 mg/day) or placebo for 12 weeks followed by an optional 12-month open-label extension. Measurements and 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 armodafi nil showed signifi cant improvement in sleep latency from baseline to fi nal 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 armodafi nil, compared to 38% on placebo. ESS and TBI-WIS scores were not signifi cantly 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. Armodafi nil was generally well tolerated, with headache the most common adverse event in both double-blind and openlabel portions. Conclusions: Armodafi nil 250 mg signifi cantly improved sleep latency in patients with excessive sleepiness associated with mild or moderate TBI. Effi cacy and tolerability of armodafi nil were sustained throughout the open-label extension.