The data presented are among the first to evaluate the efficacy, tolerability and safety of quetiapine fumarate as a monotherapy treatment for acute mania associated with bipolar disorder.1 The studies presented are from two of three Phase III trials that supported AstraZeneca's (AZN: NYSE) Supplemental New Drug Application (sNDA) for quetiapine fumarate, in the adjunctive and monotherapy treatment of acute mania associated with bipolar disorder. The sNDA for quetiapine fumarate was submitted to the U.S. Food & Drug Administration in December 2002. Quetiapine fumarate is currently indicated for the treatment of schizophrenia in adults.
"These studies present a fair evaluation of the ability of quetiapine fumarate to manage the symptoms of acute mania in patients with bipolar disorder," said Dr. Eduard Vieta, MD, PhD, Clinical Institute of Psychiatry and Psychology, Director of Bipolar Disorders Program, University of Barcelona.
Bipolar disorder, which affects about 2.3 million American adults every year, consists of recurring cycles of mania and depression.2 It is the second leading cause of neuropsychiatric disability in the world.3 Both men and women are equally at risk for this illness, which most often emerges in adolescence or young adulthood and recurs intermittently throughout life.2 More than half of those with bipolar disorder stop taking their medication at some point during their lives, subjecting them to a high risk of a relapse of symptoms and an increased risk of suicide.4
STUDY DESIGN
A pooled analysis of data from two 12-week, double-blind, randomized, placebo-controlled trials assessed the efficacy and safety of quetiapine fumarate monotherapy for the treatment of acute mania in a large cohort of adults with bipolar I disorder. A total of 604 patients experiencing a manic episode were assigned to receive quetiapine fumarate (up to 800 mg/day), placebo, lithium or haloperidol, with lithium or haloperidol serving as controls to assess assay sensitivity. The primary endpoint was change from baseline YMRS (Young Mania Rating Scale) total score at day 21 of treatment.5
CLINICAL TRIAL RESULTS
"These results and other emerging data affirm the progress and focus of several of our clinical trial programs, in which we have examined the ability of quetiapine fumarate to control acute manic episodes in patients with bipolar disorder," said Jamie Mullen, MD, Senior Director of Clinical Research, AstraZeneca. "AstraZeneca has a clear commitment to the development of new treatments for mental illness, and is proud of how successful quetiapine fumarate has been in treating patients with schizophrenia, since its launch in 1997."
ABOUT QUETIAPINE FUMARATE IN THE TREATMENT OF SCHIZOPHRENIA
The efficacy and atypical profile of quetiapine fumarate 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 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 quetiapine fumarate exhibits a low incidence of hormonal, reproductive system (sexual dysfunction), and anticholinergic side effects (dry mouth, constipation).
The labeling for quetiapine fumarate (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 quetiapine fumarate 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 quetiapine fumarate are dizziness (10%), postural hypotension (7%), dry mouth (7%), and dyspepsia (6%), and the majority of events are rated mild or moderate. The safety and effectiveness of quetiapine fumarate in pediatric patients have not been established.
Since its approval in September 1997, there have been approximately 14.3 million prescriptions written for quetiapine fumarate, or more than 3.5 million patients in the United States.5
NOTE: For full Prescribing Information for quetiapine fumarate, please visit the U.S. website at http://www.astrazeneca-us.com.
AstraZeneca (AZN: NYSE) 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 top five pharmaceutical companies in the world with healthcare sales of over $17.8 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 a $9.3 billion healthcare business with more than 12,000 employees. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit www.astrazeneca-us.com
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 Jones MW, Huizar K, et al. Quetiapine monotherapy for acute mania associated with bipolar disorder (STAMP 1 and STAMP 2). American Psychiatric Assn meeting, 2003, poster 542.
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.
4 Miklowitz D. The Bipolar Disorder Survival Guide. New York: The Guilford Press, 2002.
5 Total prescriptions from October 1997 through December 2002, NPA Plus, IMS HEALTH; Persistency Study, August 2002, NDC HEALTH.