Alexza’s Phase III agitation study meets endpoint

The AZ-004 clinical trial enrolled 344 schizophrenic patients with acute agitation at 24 US clinical centers. The trial was designed as an in-clinic, multi-center, randomized, double-blind, placebo-controlled study and tested AZ-004 at two dose levels, 5mg and 10mg. Patients were eligible to receive up to three doses of study drug in a 24-hour period, depending on their clinical status. Only one dose of study drug was allowed during the first two hours of the study period.

The primary endpoint for the study was the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component score (also known as PEC score), measured at two hours after the first dose. The key secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) score, measured at two hours after the first dose. All results were considered statistically significant at the p < 0.05 level, as compared to placebo, and all analyses were made on an intent-to-treat basis. Both the 5mg and the 10mg dose of AZ-004 met the primary endpoint of the clinical trial, showing a statistically significant improvement in the two-hour post-dose PEC score, compared to placebo. A clinical global impression-severity (CGI-S) scale rating of agitation was completed at baseline for each patient, prior to AZ-004 administration, to ensure comparability across groups. The CGI-S scale ranges from one (normal) to seven (among the most extremely agitated patients). Scores were similar across the three dose groups with a range of 3.9 to 4.1. In addition to the PEC score, the clinical global impression-improvement (CGI-I) is another commonly used scale to measure the reduction of agitation in patients over time, normally following therapeutic treatment. The CGI-I standard scale ranges from one (very much improved) to seven (very much worse). At the two-hour post-dose time point, a CGI-I scale rating was completed for each patient, which was the key secondary endpoint of the study. Both the 10mg and the 5mg doses of AZ-004 showed statistically significant differences versus placebo in the CGI-I scores at the two-hour post-dose time point. AZ-004 is an inhalation product candidate being developed for the treatment of acute agitation in patients with schizophrenia or bipolar disorder. AZ-004 is being developed through Symphony Allegro, a product development partnership formed between Alexza and Symphony Capital. Thomas King, Alexza's president and CEO, said: "These positive Phase III results, corroborating our Phase II findings, show that AZ-004 is a viable product candidate to treat acute agitation. We are very encouraged with the pace at which we have developed into a Phase III company. "In addition to our clinical successes, we are aggressively escalating many commercialization activities, including our manufacturing scale-up, quality systems, regulatory affairs and commercial operations, as we continue to track toward our planned AZ-004 NDA submission in early 2010."