TC-5214
We are currently developing TC-5214 as an augmentation therapy for major depressive disorder, or MDD. In July 2008, we initiated a Phase 2b clinical trial of TC-5214 in subjects with MDD who do not respond well based on predefined criteria to first-line treatment with citalopram hydrobromide, a marketed antidepressant from the drug class known as selective serotonin reuptake inhibitors. We have previously conducted a Phase 1 single rising dose clinical trial of TC-5214.
It is well known that depressive symptoms can result from an overstimulation of neuronal nicotinic receptors (NNRs) and other receptors in the brain that are activated by the neurotransmitter acetylcholine. Accordingly, compounds capable of inhibiting the activity of these overstimulated receptors, known as antagonists, may be expected to have antidepressant effects.
TC-5214 is the S(+) enantiomer of the racemate mecamylamine hydrochloride and a broad spectrum NNR antagonist. In 2006, we completed a Phase 2 clinical trial of mecamylamine as an augmentation therapy to citalopram. Like the current trial of TC-5214, the completed trial of mecamylamine included subjects diagnosed with MDD who did not respond well based on predefined criteria to first-line treatment with citalopram. In the completed trial, subjects whose citalopram regimen was augmented with mecamylamine showed greater improvement on symptoms of depression and irritability than subjects who received citalopram and a placebo.
TC-5214 has exhibited an overall therapeutic profile superior to mecamylamine in preclinical models of depression and anxiety (Lippiello et al., accepted for publication in CNS Neuroscience & Therapeutics), a finding consistent with laboratory studies showing TC-5214 to more effectively inhibit the activity of the alpha4beta2 NNR.
Results from the completed Phase 2 trial of mecamylamine hydrochloride were presented at the 2007 Summer Meeting of the British Association for Psychopharmacology (BAP).
Note: The poster is accessible by clicking the link at left, beneath the menu.
About Major Depressive Disorder
According to The National Institute of Mental Health (NIMH), MDD is the leading cause of disability in the United States for people between the ages 15 and 44. The NIMH estimates that approximately 14.8 million American adults suffer from MDD.
The Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study undertaken by the National Institute of Mental Health between 2001 and 2006 showed the inadequacy of currently available therapies for MDD. In the first phase of the STAR*D study, approximately 2,800 persons with MDD were given citalopram for 12 to 14 weeks. Only about one-third of the participants reached remission and about 10-15 percent more responded, but did not reach remission. The second phase of the STAR*D study evaluated the effects of augmentation with a new medication or switching to a different treatment for participants who did not respond or only responded partially to citalopram. Approximately one in four of these participants reached remission. These findings have been cited as highlighting the need for more broadly effective antidepressant treatments (Rush, et al., NEJM Volume 354:1231-1242, March 23, 2006 Number 12).