The International Journal of Neuropsychopharmacology

  • The International Journal of Neuropsychopharmacology / Volume 15 / Issue 05 / June 2012, pp 589-600
  • © CINP and Cambridge University Press 2011 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use.
  • DOI: http://dx.doi.org/10.1017/S1461145711001027 (About DOI), Published online: 18 July 2011
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Research Article

A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder

Enric Alvareza1a2, Victor Pereza1a2, Marianne Dragheima3 c1, Henrik Lofta3 and Francesc Artigasa2a4

a1 Servei de Psiquiatría, Hospital de Sant Pau, Universidat Autonoma de Barcelona, Barcelona, Spain

a2 Ministry of Science and Innovation (CIBERSAM)

a3 H. Lundbeck A/S, Copenhagen, Denmark

a4 Institut d'Investigacions Biomediques de Barcelona, CSIC, Barcelona, Spain

Abstract

The efficacy, safety, and tolerability of Lu AA21004 vs. placebo using venlafaxine XR as active reference in patients with DSM-IV-TR major depressive disorder (MDD) were evaluated. Lu AA21004 is a novel antidepressant that is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. In this 6-wk, multi-site study, 429 patients were randomly assigned (1:1:1:1) to 5 or 10 mg Lu AA21004, placebo or 225 mg venlafaxine XR. All patients had a baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥30. The primary efficacy analysis was based on the MADRS total score adjusting for multiplicity using a hierarchical testing procedure starting with the highest dose vs. placebo. Lu AA21004 was statistically significantly superior to placebo (n=105) in mean change from baseline in MADRS total score at week 6 (p<0.0001, last observation carried forward), with a mean treatment difference vs. placebo of 5.9 (5 mg, n=108), and 5.7 (10 mg, n=100) points. Venlafaxine XR (n=112) was also significantly superior to placebo at week 6 (p<0.0001). In total, 30 patients withdrew due to adverse events (AEs) – placebo: four (4%); 5 mg Lu AA21004: three (3%); 10 mg Lu AA21004: seven (7%); and venlafaxine: 16 (14%). The most common AEs were nausea, headache, hyperhidrosis, and dry mouth. No clinically relevant changes over time were seen in the clinical laboratory results, vital signs, weight, or ECG parameters. In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD.

(Received March 21 2011)

(Reviewed May 03 2011)

(Revised May 27 2011)

(Accepted June 03 2011)

(Online publication July 18 2011)

Correspondence:

c1 Address for correspondence: Dr M. Dragheim, ICR Mood & Anxiety Disorders, H. Lundbeck A/S, Ottliavej 9, DK-2500 Valby, Denmark. Tel.: +45 308 32016 Fax: +45 364 38215 Email: MAD@lundbeck.com

Footnotes

Some of the data in this article were presented in a poster at the 162nd Annual Meeting of the American Psychiatric Association, 16–21 May 2009, San Francisco, CA, USA.

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