Phase 2b study of TC-5214 as an augmentation treatment of major depressive disorder (MDD)

Targacept announced positive top-line results from their Phase 2b trial of TC-5214 as an augmentation (add-on) treatment for major depressive disorder (MDD) in subjects who did not respond adequately to first-line treatment with the selective serotonin reuptake inhibitor, Celexa (citalopram HBr, from Forest Laboratories) alone. This international, double-blind, placebo-controlled, flexible dose trial was conducted in two phases. In the first phase, 579 subjects with MDD received first-line treatment with citalopram for eight weeks. At the end of the eight weeks, subjects whose Montgomery-Asberg Depression Rating Scale score had improved less than 50 percent and was no lower than 17 and whose Clinical Global Impression - Severity of Illness score was no lower than 4 were considered partial or non-responders.  These patients were randomized into the double-blind second phase of the trial. In the double-blind second phase, patients continued their citalopram treatment and also received either add-on TC-5214 or add-on placebo for an additional eight weeks. The primary outcome measure for the trial was mean change between treatment (TC-5214 + citalopram) and placebo (placebo + citalopram) from double blind baseline as measured by the Hamilton Rating Scale for Depression-17 (HAM-D) at week 16. The primary outcome measure, the mean change between (TC-5214 + citalopram) and (placebo + citalopram) from baseline on the HAM-D, was highly statistically significant in favor of TC-5214 (p < 0.0001) on an intent to treat basis. The results on all of the trial's secondary efficacy measures, including assessments of depression, irritability, disability, cognition, severity of illness and global improvement, were also highly statistically significant in favor of TC-5214 on an intent to treat basis.

TC-5214 is a nicotinic channel blocker that has unique properties in modulating the alpha4beta2 NNR subtype. By inhibiting overstimulated NNR receptors, compounds such as TC-5214 may be expected to have antidepressant effects.

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