TARGACEPT ANNOUNCES RESULTS FROM DEPRESSION STUDY

Targacept has reported positive results from a double-blind, placebo-controlled, Phase II clinical trial of mecamylamine hydrochloride as an augmentation treatment for major depression. The trial evaluated the effects of mecamylamine taken with citalopram hydrobromide, a treatment combination known as TRIDMAC, in patients who did not respond adequately to citalopram alone. Citalopram hydrobromide is a commonly prescribed treatment for depression marketed as Celexa in the United States.

On one of two primary endpoints in the trial, patients receiving TRIDMAC showed greater improvement on symptoms of depression, as measured by group mean change from baseline on the Hamilton Depression Rating Scale (HAM-D) than patients receiving placebo with continued citalopram therapy. This result was statistically significant on an intent-to-treat basis and showed a strong trend on a per-protocol basis. The result on the trial's other primary endpoint, achievement of remission, favored the TRIDMAC group over the placebo group, although this result did not reach statistical significance. In addition, the trial included five other rating scales as secondary measures. The results on all five rating scales favored the TRIDMAC group over the placebo group with statistical significance on a per-protocol basis. On an intent-to-treat basis, the results on three of the five rating scales were statistically significant.

The trial included two phases and was conducted at one site in the U.S. and nine sites in India. In the first phase, patients with a diagnosis of major depressive disorder were given open-label citalopram hydrobromide over six weeks and evaluated based on their improvement on two scales -- HAM-D and the Clinical Global Impression subscale for severity of illness (CGI-SI) -- to determine the extent of any response. Partial and non-responders based on scores on the two scales at the end of the six-week dosing period were enrolled in the second phase, which was a double-blind, placebo-controlled trial.

In the second phase, patients received either mecamylamine or placebo, together with continued citalopram therapy, for an additional eight weeks. Patients in the mecamylamine dose group initially received 5 mg daily, titrating up to 10 mg over the dosing period at the clinician's discretion based on tolerability and therapeutic response. The primary endpoints of the trial were group mean change from baseline and achievement of remission, in each case as measured by HAM-D and compared with continued citalopram therapy plus placebo. The secondary outcome measures for the trial included rating scales to assess symptoms of depression and anxiety, disability, irritability, global improvement or severity of illness.