A failed 6-week,randomized, double-blind, placebo-controlled study of once-daily extended release quetiapine fumarate in patients with acute schizophrenia: lessons learned.

OBJECTIVE: To demonstrate the efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in adults with acute exacerbation of schizophrenia.

METHODS: A 6-week, double-blind, randomized, placebo-controlled study. In- or out-patients with a DSM-IV diagnosis of schizophrenia were randomized to fixed-dose quetiapine XR 400, 600, or 800 mg/day, quetiapine immediate release (IR) 800 mg/day, or placebo. Primary endpoint was change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Other efficacy assessments included Clinical Global Impressions (CGI) of Severity (CGI-S) and of Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures.

RESULTS: 565 patients were randomized; 333 (58.9%) completed the study. Greater numeric improvements in PANSS total score were seen for quetiapine XR (all doses) and quetiapine IR versus placebo at Week 6; the differences were not statistically significant. Secondary efficacy endpoint results were similar. There was not a high placebo response in this study, but rather an attenuation of drug effect. In general, quetiapine XR was well tolerated over 6-weeks' treatment; there were no unexpected AEs.

CONCLUSION: The efficacy of quetiapine XR (400, 600, and 800 mg/day) was not established at Week 6. Quetiapine IR, an agent with established efficacy in schizophrenia, also did not separate from placebo at endpoint. Therefore, this is considered a failed study and possible reasons for this are discussed. Quetiapine XR was generally well tolerated and its safety profile was consistent with the known profile of quetiapine.