WILMINGTON, DE -- September 13, 2002 -- A study presented for the first time today at the 3rd European Stanley Foundation Conference on Bipolar Disorder (ESFC-BD) in Freiburg, Germany, examines the use of SEROQUEL® (quetiapine fumarate) as an adjunctive medication to mood stabilizers in the treatment of acute mania in bipolar patients.
Results from this trial suggest that patients treated with SEROQUEL demonstrated a significantly greater response rate compared to the placebo group (54.3 percent and 32.6 percent, respectively). The data are the first in a series of Phase III trials that examines the efficacy, tolerability and safety of SEROQUEL in the treatment of acute mania.(1)
SEROQUEL, a product of AstraZeneca, is indicated for the treatment of schizophrenia in adults.
"The trial results suggest that SEROQUEL may be an option in treating acute mania and the psychotic symptoms often associated with it," said Gary Sachs, MD, Harvard Medical School, and lead investigator in the study presented today. "More patients treated with SEROQUEL experienced a full resolution of their manic symptoms compared to placebo (45.7 percent vs. 25.8 percent respectively based on the Young Mania Rating Scale (YMRS) scores)."(1)
Bipolar disorder, which affects about 2 to 3 million American adults every year, consists of recurring cycles of mania and depression.(2) It is currently the sixth leading cause of disability in the world.(3) Both men and women are equally at risk of this illness, which emerges in adolescence or young adulthood and continues to occur intermittently throughout life.(2)
"Current treatment options for patients with acute mania are limited and common therapies such as mood stabilizers are often less effective and associated with troublesome side effects," commented Dr. Sachs. "As a result, patient compliance with treatment can be challenging. The true value of a treatment such as SEROQUEL lies in its potential to improve the symptoms of the disease while keeping side effects to a minimum."
CLINICAL TRIAL RESULTS(1)
Results from this double blind, placebo controlled trial show that patients treated with SEROQUEL had a significantly greater response rate compared to the placebo group (54.3 percent and 32.6 percent, respectively, p=.003), a significantly greater change from baseline in their Young Mania Rating Scale (YMRS) scores compared with patients taking mood stabilizers alone (-13.76 and -9.93 respectively, p=0.021), and a significantly greater change in their Clinical Global Impressions (CGI) severity of illness scores compared to patients taking mood stabilizer alone (-1.38 and -0.78 respectively, p=.001). Discontinuations, including withdrawals for adverse events, were higher in the placebo group (51.0 percent) than the SEROQUEL group (35.5 percent)
Adverse events occurring in at least 10 percent of patients were somnolence (40 percent vs. 10 percent), headache (27 percent vs. 21 percent), dry mouth (19 percent vs. 4 percent), asthenia (11 percent vs. 3 percent), postural (orthostatic) hypotension (11 percent vs. 13 percent), and dizziness (10 percent vs. 6 percent), for SEROQUEL versus placebo, respectively, in each case.
STUDY DESIGN(1)
This three week, double blind, randomized, placebo controlled trial is the first to examine the efficacy, tolerability and safety of SEROQUEL as an adjunctive medication in the treatment of acute mania in adults. One hundred ninety-one patients diagnosed with Bipolar I Disorder and experiencing a manic episode were randomly assigned to treatment with SEROQUEL or placebo. Mood stabilizers such as lithium or divalproex were assigned unblinded prior to randomization. Patients using SEROQUEL received an average mean dose of 500 mg per day and the mood stabilizers were titrated to therapeutic levels.
The primary efficacy endpoint was a change from baseline in YMRS total score at final assessment (day 21 or the last observation carried forward). The secondary endpoints consisted of response rate, defined as the proportion of patients showing at least a 50 percent decrease in the YMRS at final assessment; remission rate, defined as YMRS score of 12 points or less at final assessment; change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS), CGI-BP Severity of Illness score, and Global Assessment Scale (GAS) score; and Positive and Negative Syndrome Scale (PANSS) including total, activation, and aggression risk subscales.
ABOUT SEROQUEL
The efficacy and atypical profile of SEROQUEL is supported by several placebo- and comparator-controlled Phase II and Phase III clinical trials in patients with schizophrenia. In clinical trials, efficacy was demonstrated in a dose range of 150mg/day to 750mg/day. An initial target dose range of 300-400mg can be given in two divided doses daily. In studies supporting the approval of SEROQUEL® (quetiapine fumarate) Tablets, there were no differences from placebo across the clinical dose range in the incidence of EPS, including rigidity and difficulty starting and stopping movement, or in elevation of serum prolactin levels. In addition, studies have shown that SEROQUEL exhibits a low incidence of hormonal, reproductive system (sexual dysfunction), and anticholinergic side effects (dry mouth, constipation).
The labeling for SEROQUEL® (quetiapine fumarate) Tablets includes a warning relative to a condition known as tardive dyskinesia (which is often associated with long-term use of antipsychotic agents) and a rare condition known as neuroleptic malignant syndrome (NMS symptoms include muscle rigidity, fever, and irregular pulse). Labeled precautions include orthostatic hypotension and the possible risk of cataract development. As with other antipsychotics, therapy with SEROQUEL should be used cautiously in patients with a history of seizures or with conditions that can potentially lower the seizure threshold.
The most common adverse events associated with the use of SEROQUEL are dizziness (10 percent), postural hypotension (7 percent), dry mouth (7 percent), and dyspepsia (6 percent), and the majority of events are rated mild or moderate. The safety and effectiveness of SEROQUEL in pediatric patients have not been established.
Since its approval in September of 1997, there have been approximately 11.6 million prescriptions written for SEROQUEL, or more than three million patients in the United States.
ABOUT ASTRAZENECA
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $16.4 billion and leading positions in sales of gastrointestinal, oncology, anesthesia (including pain management), cardiovascular, central nervous system (CNS) and respiratory products. In the United States, AstraZeneca is an $8.7 billion healthcare business with more than 10,000 employees.
This press release contains forward-looking statements with respect to AstraZeneca's business. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the company's Annual Report/Form 20-F for 2001.
REFERENCES
(1) Sachs G, Mullen JA, Devine NA. Quetiapine vs Placebo as Adjunct to Mood Stabilizer for the treatment of acute mania. Stanley Foundation Bipolar Conference, 2002, abs.
(2) Kramlinger, K. Mayo Clinic on Depression. Rochester, Minn.: Mayo Clinic Health Information, 2001.
(3) World Health Organization and the World Bank. The Global Burden of Disease: Summary. Cambridge, Mass: The Harvard School of Public Health Harvard University Press, 1996.
SOURCE: AstraZeneca
