Alexza Pharmaceuticals, Inc. (Nasdaq: ALXA) announced today that the British Journal of Psychiatry, a publication of the Royal College of Psychiatrists, has published the results of the pivotal Phase 3 study evaluating AZ-004 (inhaled or Staccato® loxapine) for the rapid treatment of agitation in patients with schizophrenia, in its January 2011 edition (198:51-58).
The Phase 3, randomized, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov), conducted in 24 U.S. clinical centers, enrolled 344 patients with schizophrenia experiencing agitation. Patients received one, two or three doses of AZ-004 (5 or 10 mg) or a placebo. Alexza previously announced preliminary results from its two Phase 3 studies in late 2008.
"Individuals with schizophrenia are highly vulnerable to episodes of agitation. Current treatment options are not optimal for managing these episodes," commented Dr. Michael D. Lesem, the publication's lead author, a principal investigator for the Phase 3 trial and Medical Director at Claghorn-Lesem Research Clinic, Houston, Texas. "There is a clear need for novel anti-agitation treatments that are quick to act, safe and well tolerated, easy to administer and accepted by patients and staff. In this study, inhaled loxapine provided a rapidly calming effect in agitated patients with schizophrenia."
The primary efficacy end-point of this study was change from baseline in PANSS (Positive and Negative Syndrome Scale) Excited Component score (also known as PEC score), measured at two hours after the first dose of study medication. The PEC score is a summation of individual scores (from 1-7) across five items: hostility, uncooperativeness, impulse control, tension, and excitement. The range of possible PEC scores is 5 through 35.
The key secondary end-point in the study was the Clinical Global Impression–Improvement scale (CGI–I) score, measured at two hours after the first dose of study medication. The four-point scale measures improvement by the physician's assessment, where 1 is very much improved and 4 is no change. A score of 2 is much improved.
Results of the study demonstrated that AZ-004 (both 5 and 10 mg) provided a statistically significant reduction in agitation compared to placebo, as assessed by the primary and key secondary end-points. A statistically significant reduction in the PEC score was evident 10 minutes after dose one with both 5 and 10 mg doses, which was the first time point assessed in the study. AZ-004 was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications.
"We are pleased to have this Phase 3 clinical trial published in a peer-reviewed journal of the caliber of the British Journal of Psychiatry," said Dr. James V. Cassella, Alexza Senior Vice President, Research and Development. "Based on the results of the robust clinical development program for AZ-004 to date, we are looking forward to our planned resubmission of the AZ-004 NDA in the U.S. in July of this year and the submission of the MAA in Europe in the third quarter."
The open access article is available on the British Journal of Psychiatry's website at: http://bjp.rcpsych.org/cgi/content/full/198/1/51.
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