LONDON, March 18 /PRNewswire/ -- AstraZeneca today announced SEROQUEL(R) sustained release formulation (quetiapine fumarate sustained release) clinical trial data presented at the European Congress of Psychiatry (ECP) in Madrid. The data demonstrated that the SEROQUEL(R) sustained release formulation (quetiapine fumarate sustained release), administered once daily, significantly improved symptoms associated with schizophrenia(1) (measured by PANSS) and increased the time to psychiatric relapse(2), when administered through a 3-step dose initiation aimed at reaching the effective dose range on the second day of treatment.
SEROQUEL(R) sustained release formulation is under review by regulatory authorities around the world for the treatment of schizophrenia and has not been approved in any market.
A randomized, double-blind study of 588 patients with acute schizophrenia (Study 132) compared SEROQUEL(R) sustained release formulation (400 mg/day, 600 mg/day or 800 mg/day) with placebo and found a significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline for all doses.(1) After 6 weeks of treatment, reductions of 24.8 (p=0.03), 30.9 (p<0.001), and 31.3 (p<0.001) points were seen with 400, 600, and 800 mg doses, respectively, compared with a reduction of 18.8 points for placebo. Patients on SEROQUEL(R) sustained release formulation also had significantly better scores on the Clinical Global Impression (CGI)-Severity scale and significantly more patients showed improvement on the CGI-Improvement scale compared to placebo.
A second randomized, double-blind placebo controlled study (Study 004) examined time to first psychiatric relapse in 197 patients with clinically stable schizophrenia treated with either SEROQUEL(R) sustained release formulation (mean dose 669 mg/day) or placebo(2). Patients treated with SEROQUEL(R) sustained release formulation experienced a significantly reduced risk of relapse (risk reduction of 87%, p<0.0001), and a significantly longer time to relapse, compared with those on placebo. Differences in relapse rate between active treatment and placebo were large enough to require the study to be stopped early, in accordance with the study protocol. In the SEROQUEL(R) sustained release group, the estimated risk of relapse after 6 months was 14.3% versus 68.2% in the placebo group (p<0.0001). Hospitalization due to worsening of schizophrenia was required by 8.3% of patients on placebo, but was not needed for any patients taking SEROQUEL(R) sustained release formulation.
Professor Rene Kahn, Professor and Chair of the Department of Psychiatry and Head of the Division of Neuroscience at the University Medical Center, Utrecht, said: "In these studies SEROQUEL(R) sustained release formulation showed its potential as a once-daily treatment for both acute and clinically stable schizophrenia. Statistical significance on the primary endpoint was seen at doses between 400 and 800 mg/day and patients achieved that range within two days of starting treatment - that is an advantage over original formulation quetiapine, where the initial dose escalation is not so simple. In mental healthcare, striving for treatment that is simpler and more practical is an important objective for patients and doctors."
In both studies, somnolence and dizziness were the most common adverse events with SEROQUEL(R) sustained release formulation and these were generally mild or moderate, transient, and did not lead to withdrawal from the trials. The incidence of extrapyramidal adverse events was similar to placebo (EPS-related adverse events were seen in 5.1% of patients taking placebo versus 2.7% [400mg], 8.0% [600mg] and 4.1% [800mg] of patients taking SEROQUEL(R) sustained release formulation in the acute study(1)).
Other new SEROQUEL(R) sustained release formulation studies presented at the congress show that patients who are currently receiving original formulation quetiapine, or who are inadequately treated with another antipsychotic agent, could be easily switched to SEROQUEL(R) sustained release formulation. Among clinically stable patients who switched from original formulation quetiapine, there were no significant differences between SEROQUEL sustained release formulation and the original formulation quetiapine in PANSS total scores after 6 weeks treatment (mean PANSS total score at day 42 was 55.4 and 54.8 for the sustained release formulation and the original formulation respectively) and the incidence of adverse events was similar (Study 146). (3) Among patients who switched to SEROQUEL(R) sustained release formulation from other antipsychotics, 62.8% achieved improved clinical benefit (based on CGI-CB scores) regardless of the reason for switching (insufficient efficacy or intolerability of initial treatment, Study 147) (4).
Based on these data and data from other trials, regulatory filings for the treatment of schizophrenia with SEROQUEL(R) sustained release formulation were submitted to the authorities in the US, EU and other markets in 2006. Beyond schizophrenia, ongoing clinical studies of SEROQUEL(R) sustained release formulation cover bipolar disorder, major depressive disorder and generalized anxiety disorder. SEROQUEL(R) (original formulation quetiapine) is the number 1 prescribed atypical antipsychotic in the United States and global sales for SEROQUEL(R) reached US$3.4 billion in 2006. It is licensed in 85 countries for the treatment of schizophrenia, in 73 countries for the treatment of mania associated with bipolar disorder, and in October 2006 it was approved in the US by the FDA for the treatment of bipolar depression. It is estimated that more than 19 million patients have used SEROQUEL(R) worldwide since its launch in 1997.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of US$26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index.
References
1. Kahn R, et al. Efficacy and tolerability of once daily quetiapine sustained release in patients with acute schizophrenia: a randomised, double blind, 6 week, placebo-controlled study. Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.
2. Peuskens J, et al. Randomised, placebo-controlled, relapse-prevention study with once-daily quetiapine sustained release in patients with schizophrenia. Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.
3. Möller H-J, et al. Continued efficacy and tolerability in clinically stable patients switched from quetiapine immediate release (IR) to quetiapine sustained release (SR). Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.
4. Ganesan S, et al. Clinical benefit of switching patients with schizophrenia to once-daily quetiapine sustained release. Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.
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