The efficacy, safety, and tolerability of Lu AA21004 versus placebo, using 
duloxetine as active reference, in patients with DSM-IV-TR diagnosed major 
depressive disorder (MDD) were evaluated in this 8-week, multi-site study. 
Patients (n=766) had a baseline Montgomery-Åsberg Depression Rating Scale 
(MADRS) total score ≥26 and were randomly assigned (1:1:1:1:1) to 2.5, 5 or 10 
mg Lu AA21004, placebo, or 60 mg duloxetine. The 5mg and 10mg doses of Lu 
AA21004 were tested separately versus placebo at p≤0.025 in a pre-specified 
order. In the pre-defined primary efficacy analysis [mean change from baseline 
in MADRS total score at Week 8, full analysis set, ANCOVA, last observation 
carried forward (LOCF)], the differences to placebo (n=145) of -1.7 (Lu AA21004 
5 mg, n=155) and -1.5 points (Lu AA21004 10 mg, n=151) were not statistically 
significant; nor were those for Lu AA21004 2.5 mg (-1.4 points, n=155) or 
duloxetine (-2.0 points, n=149). Using mixed model, repeated measures (MMRM) 
analyses of the primary endpoint and most secondary endpoints were supportive of 
likely efficacy for Lu AA21004 5 mg and 10 mg and duloxetine. Treatment-emergent 
adverse events led to the withdrawal of 72 patients: 8% (placebo), 12% 
(duloxetine), and 6%, 11% and 9% in the Lu AA21004 groups (2.5 mg, 5 mg and 10 
mg, respectively). The most common adverse events were nausea, headache, 
dizziness, and dry mouth. No clinically relevant changes were seen in vital 
signs, weight, ECG, or laboratory results. In summary, none of the active 
treatment groups, including duloxetine, separated from placebo in the primary 
analysis in this 'failed' study. Findings on secondary outcome measures, using 
MMRM instead of LOCF, were supportive of likely efficacy for Lu AA21004 5mg and 
10mg and duloxetine. Lu AA21004 (2.5, 5 and 10 mg) was well tolerated.