Targacept has presented data from its recently completed phase 2b clinical trial of TC-5214 as an augmentation (add-on) treatment in subjects with major depressive disorder, or MDD. Reportedly, it did not respond adequately to first-line treatment with the representative SSRI citalopram hydrobromide.
In the trial, the add-on TC-5214 arm (TC-5214 + citalopram) outperformed the add-on placebo arm (placebo + citalopram) on the primary outcome measure, the Hamilton Rating Scale for Depression-17, or HAM-D, and all of the secondary outcome measures, with high statistical significance.
Selective serotonin reuptake inhibitors, or SSRIs, are the most commonly prescribed class of drugs for depression, but many patients do not respond well to SSRIs. The phase 2b trial of TC-5214 as an augmentation treatment for MDD was a two-phase study conducted at 20 sites in India and three sites in the US.
In the double blind second phase, subjects continued their citalopram treatment and also received either add-on TC-5214 or add-on placebo for an additional eight weeks. In the TC-5214 trial, the magnitude of clinical response (change from double blind baseline after eight weeks) on HAM-D was 6.0 points greater for the add-on TC-5214 arm (13.75 point improvement) than for the add-on placebo arm (7.75 point improvement).
The result suggested that the trial was significant on an intent to treat basis. The significant results were also achieved on an intent to treat basis on all of the trial’s secondary outcome measures, including the Montgomery-Asberg Depression Rating Scale, or MADRS, the Quick Inventory of Depressive Symptomatology – Self Reporting scale and assessments of irritability, disability, cognition, severity of illness and global improvement.
The data from the TC-5214 trial was presented by Geoffrey Dunbar, vice president, Clinical Development and Regulatory Affairs of Targacept, at the Nicotinic Acetylcholine Receptors as Therapeutic Targets Symposium (nAChR2009), a satellite meeting of the 39th annual meeting of the Society for Neuroscience.
Donald deBethizy, president and CEO of Targacept, said: “We are excited about the potential of TC-5214 to provide a new mechanistic approach for the treatment of depression. The STAR*D study indicates that nearly two-thirds of subjects do not achieve full relief from depressive symptoms on their initial SSRI medication, and we believe that a well tolerated add-on treatment with strong antidepressant effects would represent a major breakthrough.”