AstraZeneca and Targacept Inc. has released top-line results from the first of four RENAISSANCE phase III studies investigating the efficacy and tolerability of TC-5214 as an adjunct therapy to an antidepressant in patients with major depressive disorder (MDD) who do not respond adequately to initial antidepressant treatment.

The study did not meet its primary endpoint of change on the Montgomery-Asberg Depression Rating Scale (MADRS) after eight weeks of treatment with TC-5214 as compared to placebo.

TC-5214 was overall well tolerated in the study and showed an adverse event profile generally consistent with the earlier phase II b study. Analyses of the full data set from the RENAISSANCE 3 study remain ongoing.

The RENAISSANCE clinical trial programme consists of four randomised, double blind, placebo controlled phase III efficacy and tolerability studies and a fifth long-term safety study. The results released are from the RENAISSANCE 3 study, a flexible dose trial conducted in Europe. All RENAISSANCE phase III studies have now completed enrolment, and reporting of all results is expected by the first half of 2012.

TC-5214 has the potential to be a first-in-class nicotinic channel modulator to serve as an adjunct treatment for MDD in patients with an inadequate response to initial antidepressant therapies, for example, selective serotonin reuptake inhibitors (SSRIs) or serotonin/norephinephrine reuptake inhibitors (SNRIs).

An NDA filing in the US is planned for the second half of 2012, with an MAA filing in the EU targeted for 2015.

In December 2009, AstraZeneca and Targacept signed a collaboration and license agreement for the global development and commercialisation of TC-5214. The initial goal for the collaboration is to develop TC-5214 as an adjunct treatment for MDD in patients with an inadequate response to an SSRI or SNRI.

The MADRS is a commonly used 10-item questionnaire that psychiatrists employ to measure the severity of depressive episodes in patients with mood disorders.

Targacept is developing a diverse pipeline of innovative NNR Therapeutics for difficult-to-treat diseases and disorders of the nervous system.