AstraZeneca and Targacept have reported the data from the remaining Phase III studies evaluating the efficacy, tolerability and safety of TC-5214 as an adjunct therapy to an antidepressant in patients with major depressive disorder (MDD).
TC-5214 is being investigated in the Renaissance Programme, which included five randomised double blind placebo controlled Phase III studies.
In Renaissance study 4, a total of 2,407 patients with MDD were screened, of which 1,335 initially received one of seven selective serotonin reuptake inhibitor's (SSRI) or serotonin/norepinephrine reuptake inhibitor's (SNRI) on an open label basis for eight weeks to determine the extent of therapeutic response.
At the end of the eight weeks, 641 patients who did not respond were randomised into the double blind phase of the study and received either 0.5mg, 2mg and 4mg BID twice daily TC-5214 or placebo while continuing the SSRI or SNRI therapy for an additional eight weeks.
A total of 1,566 patients with MDD were screened in Renaissance study 5, of which 1,285 patients received one of seven SSRIs or SNRIs on an open label basis for eight weeks to determine the extent of therapeutic response.
In Renaissance study 5, 696 patients who did not respond were randomised into the double blind phase of the study and received either 0.1mg, 1mg and 4mg BID TC-5214 or placebo.
The 1,934-patient Renaissance flexible dose trial 7 randomised 808 patients to receive one to four mg BID TC-5214 or placebo, plus one of seven SSRIs or SNRIs, for up to one year.
Both efficacy and tolerability studies, Renaissance 4 and Renaissance 5, did not meet the primary endpoint of change on the Montgomery-Asberg Depression Rating Scale (MADRS) total score after eight weeks of adjunct treatment with TC-5214 as compared to placebo.
In Renaissance study 7, TC-5214 was overall well tolerated, with an adverse event profile consistent with the prior clinical trials.
As the studies failed to meet the endpoint, AstraZeneca and Targacept will not pursue a regulatory filing for TC-5214 as an adjunct treatment for patients with MDD.