A 6-week randomized, placebo-controlled trial of CP-316,311 (a selective CRH1 antagonist) in the treatment of major depression.
OBJECTIVE
The corticotropin-releasing hormone (CRH) system is implicated in the pathogenesis of several psychiatric disorders, including major depressive disorder. This study was designed to evaluate the safety and efficacy of CP-316,311, a selective nonpeptide antagonist of corticotropin-releasing hormone type 1 (CRH(1)) receptors, in the treatment of recurrent major depressive disorder.


METHODS
Of a total of 167 patients with recurrent major depression who were screened, 123 were randomly assigned to receive 400 mg of CP-316,311 twice daily, or 100 mg of sertraline daily, or placebo in a 6-week fixed-dose, double-blind, double-dummy, parallel-group, placebo- and sertraline-controlled trial. The primary efficacy analysis compared the change in score from baseline to endpoint on the 17-item Hamilton Depression Rating Scale (HAM-D) between the CP-316,311 and placebo groups. A group sequential design was used to support early trial termination based on efficacy or futility at a planned interim analysis.


RESULTS
The evaluable data set for the interim analysis included 28 patients in the CP-316,311 group, 31 patients in the placebo group, and 30 patients in the sertraline group. In the interim analysis, the change from baseline in the HAM-D score at the final visit was not significantly different between the CP-316,311 and placebo groups, while change from baseline between the sertraline and placebo groups was significantly different. Given these results, futility was declared for CP-316,311 and the trial was terminated.


CONCLUSIONS
Although CP-316,311 was safe and well tolerated in this study population, it failed to demonstrate efficacy in the treatment of major depression.
Binneman
Brendon
B
Pfizer Global Research and Development, M.S. 8260-2604, Groton, CT 06340, USA. brendon.binneman@pfizer.com
Feltner
Douglas
D
Kolluri
Sheela
S
Shi
Yuanjun
Y
Qiu
Ruolun
R
Stiger
Thomas
T
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D020280:Sertraline / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D000099052:CRF Receptor, Type 1
D000928:Antidepressive Agents; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D020280:Sertraline