A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder.

OBJECTIVE: Lu AA21004 is an investigational multimodal antidepressant. This randomized controlled trial evaluated the efficacy and tolerability of multiple doses of Lu AA21004 versus placebo in adults with major depressive disorder (MDD).

METHOD: Adults diagnosed with MDD (based on DSM-IV-TR criteria) with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 26 were randomly assigned (1:1:1:1) to receive Lu AA21004 1 mg, 5 mg, or 10 mg or placebo for 8 weeks (between August 2008 and August 2009). The primary endpoint was reduction in 24-Item Hamilton Depression Rating Scale (HDRS-24) total score after 8 weeks of treatment compared with placebo for Lu AA21004 10 mg. Additional outcomes included response and remission rates, Sheehan Disability Scale (SDS), Clinical Global Impressions-Global Improvement scale (CGI-I), MADRS total score, and HDRS-24 total score in subjects with baseline Hamilton Anxiety Rating Scale (HARS) score ≥ 20. Adverse events were assessed throughout the study.

RESULTS: A total of 560 subjects (mean age = 46.4 years) were randomized. There was a statistically significant reduction from baseline in HDRS-24 total score at week 8 for Lu AA21004 10 mg vs placebo (P < .001). There were improvements (nominal P values < .05 with no adjustment for multiplicity) in HDRS-24 total score, response and remission rates, CGI-I score, MADRS total score, and HDRS-24 total score in subjects with baseline HARS score ≥ 20 at week 8 for all Lu AA21004 treatment groups vs placebo. No significant differences were seen in SDS scores between any dose of Lu AA21004 and placebo. The most common adverse events were nausea, headache, and dizziness.

CONCLUSIONS: After 8 weeks of treatment with Lu AA21004 10 mg, there was a significant reduction in HDRS-24 total score compared with placebo in adults with MDD. Lu AA21004 was well tolerated in this study.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00735709.