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Psych Congress  

An Adjunctive Clinical Trial Design to Examine Efficacy and Safety of Armodafinil for Major Depressive Episodes Associated With Bipolar I Disorder

James G. King, PhD. Joseph R. Calabrese, MD. Mark A. Frye, MD. Ronghua Yang, PhD. Terence A. Ketter, MD.
Teva Pharmaceutical Industries Ltd

Background: Patients in randomized, controlled trials of bipolar depression generally do not represent the patient population with the disorder. This report describes the study design and baseline patient characteristics of a phase 3 study examining the safety and efficacy of adjunctive armodafinil therapy for major depressive episodes associated with bipolar I disorder (NCT01072929). 
Methods: This 8-week, double-blind, placebo-controlled, multicenter study evaluated a heterogeneous sample of adults with bipolar I disorder who were currently experiencing a major depressive episode while on 1 or 2 of the following maintenance therapies: lithium, valproate, olanzapine, aripiprazole, risperidone, lamotrigine, or ziprasidone (ziprasidone only in combination with lithium or valproate) for at least 4 weeks prior to the onset of the depressive episode. 
Results: Of 786 patients screened across 70 centers, 433 were randomized (placebo [n=199], armodafinil 150 mg [n=201], and armodafinil 200 mg [n=33]). The 200 mg armodafinil group was discontinued early by protocol amendment. Baseline disease severity, as assessed by mean (SD) IDS C30 total scores, was characteristic of severe depression (43.7 [6.9] and 43.1 [7.7] for the placebo and 150 mg groups, respectively). The most common concomitant treatments were valproate, lithium, and lamotrigine. A large proportion of patients was previously hospitalized for bipolar depression (placebo, 71% [142/199]; armodafinil 150 mg, 64% [129/201]). 
Conclusions: This noteworthy study design allowed for a wide range of adjunctive maintenance treatments at study entry, more accurately modeling the diversity of clinical presentations treated in community settings. The study design achieved adequate assay sensitivity, but with markedly improved external validity/generalizability.

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