The first of three phase III trials examining the investigational agent mifepristone as treatment for the psychotic features of psychotic major depression has produced negative results.

Study 07 was a randomized, double-blind, placebo-controlled study. The primary endpoint, a responder analysis, was the proportion of patients with at least a 50 percent improvement in the Brief Psychiatric Rating Scale Positive Symptom Subscale (BPRS PSS) at both Day 7 and Day 56.

Specifically, the Subscale is an 18-item rating instrument used to assess psychopathology, and the Positive Symptom Subscale is a subset of four items that specifically measure psychosis.

Researchers found that 30.5 percent of patients receiving mifepristone and 28.6 percent of patients receiving placebo were responders. The two key secondary endpoints were similarly negative.

"There was an unusually high placebo response rate in this trial," noted Robert L. Roe, MD, President and head of development of the drug manufacturer. "At Day 56, for example, approximately 80 percent of the patients in both of the arms of the study were responders as measured by a 50 percent improvement in BPRS PSS score."

Joseph K. Belanoff, MD, also with the manufacturer, noted that Study 09, which completed its enrollment of 247 patients in late May, will have its results released soon.

Mifepristone, a selective antagonist of cortisol and progesterone receptors, has had promising results when used for psychosis and depression in patients with Cushing’s disease.