AstraZeneca and Targacept announced the initiation of a Phase2b clinical trial of TC-5214 as a “switch” monotherapy treatment for patients with MDD who do not respond adequately to initial antidepressant therapy. In the study, patients with MDD who do not respond adequately to initial open label treatment with one of six commonly used selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors will be switched to receive either one of two fixed doses of TC-5214, duloxetine, or placebo. The primary endpoint is the change from double-blind baseline at the end of the dosing period for TC-5214 on the Montgomery-Åsberg Depression Rating Scale (MADRS) as compared to placebo.
TC-5214 is nicotinic channel blocker that modulates the activity of certain neuronal nicotinic receptors (NNRs) to normalize cholinergic tone. Depressive symptoms are associated with increased cholinergic tone caused by an overstimulation of NNRs and other receptors in the brain that are activated by acetylcholine.