WILMINGTON, Del., May 23 /PRNewswire-FirstCall/ -- AstraZeneca today announced results presented at the annual meeting of the American Psychiatric Association (APA) from a large-scale study called BOLDER (BipOLar DEpRession) II, which examined SEROQUEL(R) (quetiapine fumarate) as a monotherapy treatment for depressive episodes in patients with bipolar I and II disorders. Results from this clinical trial showed significant improvement in measures of depressive symptoms in patients taking SEROQUEL, confirming the results of the BOLDER I study.(1,5) An additional analysis of the BOLDER studies presented at APA evaluated the effect of SEROQUEL on suicidality in patients with bipolar depression.(2) SEROQUEL is currently approved for the treatment of acute manic episodes associated with bipolar I disorder and the treatment of schizophrenia.
"Results from BOLDER II are remarkably similar to those found in BOLDER I, the first large-scale study that examined SEROQUEL treatment of depressive episodes in bipolar I and II patients. The replication of BOLDER I by BOLDER II adds considerable strength to the BOLDER data," said Michael E. Thase, M.D., Lead Investigator of BOLDER II and Professor of Psychiatry, University of Pittsburgh Medical Center. "In the past, doctors have typically treated bipolar disorder with both a mood stabilizer and an antidepressant. Having a single medication to treat both the manic and depressive episodes of this condition would be a significant medical advance."
The depressive phase of bipolar disorder is characterized by prolonged periods of sadness, loss of energy, persistent lethargy and/or recurring thoughts of death or suicide.(3) People with bipolar disorder are symptomatic almost half of their lives, and approximately two-thirds of that time is spent in the depressed phase of the illness.(4) Up to 20 percent of patients with bipolar disorder commit suicide,(12) and up to 50 percent have attempted suicide at least once.(11)
On December 30, 2005, AstraZeneca submitted a supplemental New Drug Application (sNDA) with the US Food and Drug Administration (FDA) to seek approval for SEROQUEL(R) in the treatment of patients with depressive episodes associated with bipolar disorder.
About the study, a poster presentation entitled: Confirmation of the Efficacy of Quetiapine Monotherapy in Bipolar Depression in a Second Double- Blind, Placebo-Controlled Study: The BOLDER II Study(1)
In BOLDER II, depressed patients (n=509) with bipolar I or II disorder were randomized to 8 weeks of double-blind treatment with SEROQUEL (300 or 600 mg/day) or placebo. Patients were assessed weekly using MADRS (Montgomery- Asberg Depression Rating Scale)+ and HAM-D (Hamilton Rating Scale for Depression)++ rating scales. The primary endpoint was the reduction in MADRS total score from baseline at Week 8.(1)
Results showed that the mean reduction from baseline in the MADRS total score was significantly greater with SEROQUEL than with placebo as early as Week 1 (mean change with SEROQUEL 300 mg/day = -9.42 and 600 mg/day = -9.14; both P<.001 versus placebo = -6.10), with continued improvement through Week 8 (mean change with SEROQUEL 300 mg/day = -16.94 and 600 mg/day = -16.00; both P<.001 versus placebo: -11.93).(1)
Reduction in mean HAM-D total score was significantly greater with both SEROQUEL(R) doses than with placebo as early as Week 1 (P<.001), with improvement continuing through the study's endpoint. There were significant improvements demonstrated in other secondary outcome measures as well. At the study's endpoint (Week 8), a significantly greater percentage of patients was classified as responders* with SEROQUEL 300 mg/day (60.0%) and 600 mg/day (58.3%) than with placebo (44.7%; P<.01 and <.05, respectively). In addition, remission** was achieved at Week 8 in a significantly greater percentage of patients with SEROQUEL vs. placebo (SEROQUEL 300 mg/day = 51.6% and SEROQUEL 600 mg/day = 52.3%, P<.05 and <.01 respectively, vs placebo = 37.3%).(1)
Common adverse events with SEROQUEL in BOLDER II included dry mouth (300 mg/day: 42.7%, 600 mg/day: 47.0%, placebo: 18.0%), sedation (32.2%, 27.4%, 10.2%), somnolence (29.8%, 29.8%, 4.8%), and dizziness (14.0%, 16.1%, 5.4%). Generally, adverse events were mild to moderate in intensity; discontinuation rates due to adverse events were 8.2% (300 mg/day), 11.3% (600 mg/day), and 1.2% (placebo).(1) Rates of treatment-emergent mania were low and similar to placebo: 1.8% with SEROQUEL 300 mg/day, 3.6% with SEROQUEL 600 mg/day, and 6.6% with placebo.(1)
About the study, a poster presentation entitled: Analysis of Suicidality in Patients with Bipolar Depression Treated with Quetiapine Monotherapy(2)
BOLDER I and BOLDER II also examined the effect of SEROQUEL (300 or 600 mg/day) on suicide-related symptoms in depressive episodes of bipolar disorder. In a post-hoc analysis of 1045 patients, mean MADRS item 10 score (suicidal thoughts) decreased significantly more with both SEROQUEL doses than placebo at Week 8 (300 mg/day = -.98, P<.001; 600 mg/day = -.92, P=.001, vs placebo = -.64). The decrease in HAM-D item 3 score (suicide) at Week 8 was also significantly greater with both SEROQUEL doses than with placebo (300 mg/day = -.70 and 600 mg/day = -.66; P<.001 and P=.006 respectively vs. placebo = -.50). Utilizing the Columbia criteria(S), the incidence of suicidal ideation (300 mg/day = 1.1%, 600 mg/day = .9%, placebo = 1.4%) and suicide attempts (.3%, .9% and .3%) was found to be low and similar in all three treatment groups. There were no cases of completed suicide during these two studies.(2)
"Recurring thoughts of death or suicide are often associated with bipolar depression. In fact, up to 20 percent of patients with bipolar disorder commit suicide," said Wayne Macfadden, M.D., US Medical Director for SEROQUEL(R). "These analyses of suicidality, coupled with other results from BOLDER II, further support AstraZeneca's sNDA for the use of SEROQUEL monotherapy in the treatment of depressive episodes of bipolar disorder. If approved, it would be the only single agent indicated to treat both the depressive and manic episodes associated with bipolar disorder."
SEROQUEL is the #1 prescribed atypical antipsychotic in the United States.(7) With a well-established safety and efficacy profile, SEROQUEL has had more than 16 million patient exposures worldwide since its launch in 1997. In 2005, global sales for SEROQUEL reached $2.8 billion.
IMPORTANT SAFETY INFORMATION
SEROQUEL is indicated for the treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy with lithium or divalproex, and the treatment of schizophrenia. Patients should be periodically reassessed to determine the need for continued treatment. SEROQUEL is not approved for the treatment of bipolar depression or the prevention of suicide.
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death compared to placebo (4.5% vs 2.6%, respectively). SEROQUEL is not approved for the treatment of patients with dementia-related psychosis.
Prescribing should be consistent with the need to minimize the risk of tardive dyskinesia. A rare condition referred to as neuroleptic malignant syndrome has been reported with this class of medications, including SEROQUEL.
Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including SEROQUEL. Patients starting treatment with atypical antipsychotics who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.
Precautions include the risk of seizures, orthostatic hypotension and cataract development.
The most commonly observed adverse events associated with the use of SEROQUEL(R) in clinical trials were somnolence, dry mouth, dizziness, constipation, asthenia, abdominal pain, postural hypotension, pharyngitis, SGPT increase, dyspepsia, and weight gain.
For full prescribing information for SEROQUEL, please visit the website http://www.seroquel.com.
ABOUT BIPOLAR DISORDER
Bipolar I disorder is characterized by the occurrence of one or more manic episodes or mixed episodes. Often individuals have also had one or more major depressive episodes. Bipolar II disorder is characterized by the occurrence of one or more major depressive episodes accompanied by at least one hypomanic episode.(8) In the long term, patients with bipolar I disorder experience depressive symptoms three times longer than manic symptoms.(4) Patients with bipolar II disorder have traditionally been difficult to treat as they spend almost forty times longer in the depressed state than hypomania.(9) Without appropriate treatment, patients usually suffer for a lifetime with periods of wellness and functioning punctuated by severe episodes of illness. Both men and women are equally at risk for this illness, which most often emerges in adolescence or young adulthood and recurs throughout life.(10)
ABOUT ASTRAZENECA
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 $23.95 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. In the United States, AstraZeneca is a $10.77 billion healthcare business with more than 12,000 employees. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit: http://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 2005.
+ Depression scores were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS scale measures the severity of a number of depressive symptoms including mood and sadness, tension, sleep, appetite, energy, concentration, and suicidal ideation. The MADRS score decreases as depressive symptoms improve.(6) ++ Hamilton Depression Rating (HAM-D) Scale: This scale is used to assess the severity of depression in patients already diagnosed with an affective disorder. The HAM-D score decreases as depressive symptoms improve.(6) * Response rate defined as at least 50% decrease in MADRS total score from baseline(1) ** Remission defined as MADRS total score less than or equal to 12(1) S The Columbia criteria is a coding system for categorizing suicidality. (1) ME Thase, W Macfadden, R McCoy, W Chang, JR Calabrese. Confirmation of the Efficacy of Quetiapine Monotherapy in Bipolar Depression in a Second Double-Blind, Placebo-Controlled Study: The BOLDER II Study. Annual Meeting of the American Psychiatric Association, 2006, Toronto, Canada, research poster board NR600. (2) W Macfadden, E Spong, M Minkwitz. Analysis of Suicidality in Patients with Bipolar Depression Treated with Quetiapine Monotherapy. Annual Meeting of the American Psychiatric Association, 2006, Toronto, Canada, research poster board NR248. (3) Introduction to Depression and Bipolar Disorder. Depression and Bipolar Support Alliance, 730 N. Franklin Street, Suite 501, Chicago, Illinois 60610-7224. Available at: http://www.dbsalliance.org/PDF/IntroBrochureC2.pdf. Accessed May 5, 2006. (4) Judd, Lewis L. et al. The Long-term Natural History of the Weekly Symptomatic Status of Bipolar I Disorder. Arch Gen Psychiatry. 2002; 59: 530 - 537. (5) Calabrese JR, Keck PE, Macfadden W, et al, for the BOLDER Study Group. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162:1351-1360.
(6) Lundbeck Institute. Psychiatric Rating Scales. PDF available at: http://www.brainexplorer.org/factsheets/Psychiatry%20Rating%20Scales.pdf.
Accessed on May 5, 2006. (7) All atypical prescriptions: Total prescriptions Jan 06 to March 06. IMS Health. National Prescription Audit. (8) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Washington DC: 2001. (9) Judd, Lewis L. et al. A Prospective Investigation of the Natural History of the Long-term Weekly Symptomatic Status of Bipolar II Disorder. Arch Gen Psychiatry. 2003; 60: 261 - 269. (10) Kramlinger, Keith. Mayo Clinic on Depression. Rochester, MN: 2001. (11) Oquendo MA, Chaudhury SR, Mann JJ. Pharmacotherapy of Suicidal Behavior in Bipolar Disorder. Archives of Suicide Research. 9(3): 237-50, 2005. (12) Goodwin, Frederick K. and Kay Redfield Jamison. Manic Depressive Illness. New York: Oxford University Press, 1990.
AstraZenecaCONTACT: Lynn Gionta, +1-302-885-5672, lynn.gionta@astrazeneca.com, or JimMinnick, +1-302-886-5135, jim.minnick@astrazeneca.com, both of AstraZeneca
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