The EMBOLDEN studies are two similarly designed multicentre, randomised, double-blind comparisons of the efficacy and safety of SEROQUEL monotherapy (300 mg or 600 mg daily) with placebo in adult patients with bipolar I or II disorder. SEROQUEL monotherapy was significantly more effective than placebo for treating depressive episodes associated with bipolar disorder in the 8-week acute phase as measured by improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline (p<0.001 for both doses of SEROQUEL in each study). In the continuation phase lasting 26-52 weeks, treatment with SEROQUEL compared with placebo significantly increased the time to any mood event (hazard ratio 0.56; 95% CI: 0.39-0.82; p<0.05 for EMBOLDEN I and 0.43; 95% CI: 0.27-0.69; p<0.05 for EMBOLDEN II).
SPaRCLe is a multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of SEROQUEL and lithium for up to 104 weeks of maintenance treatment in adult patients with bipolar I disorder. After stabilisation on open-label SEROQUEL, 1226 patients were randomised to continue SEROQUEL (median dose 546 mg/day) or be switched to either lithium (median serum level 0.63 mEq/L) or placebo. In patients who continued SEROQUEL, time to recurrence of a mood event was significantly longer compared with those switched to placebo (hazard ratio 0.29; 95% CI: 0.23-0.38; P<0.001) and those switched to lithium (hazard ratio 0.66; 95% CI: 0.49-0.88; P<0.01). Switching to lithium was also more effective than switching to placebo (hazard ratio 0.46; 95% CI: 0.36-0.59; P<0.001).
Professor Alan Young of the Department of Psychiatry, University of British Columbia, Vancouver, Canada said: "Bipolar disorder is a chronic illness and patients need long-term treatment to help control their mood episodes. These new studies show that SEROQUEL monotherapy may delay the reappearance of depressed, manic or mixed events associated with bipolar disorder regardless of the type of mood event the patient is currently experiencing. This could be important for patients, because they are often faced with taking several different long-term medications to treat their illness."
Long-term treatment with SEROQUEL in the EMBOLDEN and SPaRCLe trials was generally well tolerated and adverse events were consistent with those reported in short term, placebo-controlled trials with SEROQUEL. The most common adverse events associated with SEROQUEL in the acute phase of the EMBOLDEN studies were somnolence, dry mouth and dizziness (EMBOLDEN I) and dry mouth, somnolence and sedation (EMBOLDEN II). The most commonly reported adverse events with SEROQUEL in the continuation phase included headache, nasopharyngitis, diarrhoea, somnolence and an increase in weight (EMBOLDEN I) and dry mouth, dizziness, sedation, headache and somnolence (EMBOLDEN II).
In the randomised phase of the SPaRCLE study, the most common adverse events associated with SEROQUEL were headache, somnolence and insomnia, and the most common adverse events associated with lithium were nausea, insomnia, headache and vomiting.
Other data presented at an AstraZeneca satellite symposium at ECNP highlighted the benefit of SEROQUEL when combined with a mood stabiliser (lithium or divalproex) for maintenance therapy of up to 104 weeks in patients with bipolar I disorder.4 Pooled results from two clinical studies indicated that patients treated with SEROQUEL plus lithium or divalproex had a risk reduction of 70% relative to those treated with placebo plus lithium or divalproex for time to recurrence of a mood event (hazard ratio = 0.30; 95% CI: 0.24-0.37; p<0.001).5
The most commonly reported adverse events in patients treated with SEROQUEL plus a mood stabiliser during the maintenance phase were headache, nasopharyngitis, and upper respiratory tract infection. The analysis also showed a greater incidence of fasting blood glucose increases to hyperglycaemic levels (≥126 mg/dL [7 mmol/L]) in patients randomised to SEROQUEL plus mood stabiliser (10.7%, 18.0 patients per 100 patient-years) than in patients randomised to placebo and mood stabiliser (4.6%, 9.5 patients per 100 patient-years). AstraZeneca has updated labels worldwide pursuant to local regulatory requirements to reflect the increases in blood glucose levels observed in recent trials.
Based data from these studies, in May 2008 the US Food and Drug Administration (FDA) approved SEROQUEL for the maintenance treatment of patients with bipolar I disorder, as adjunct to lithium or divalproex.
About SEROQUEL and SEROQUEL XR
Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 22 million* patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 79 countries for the treatment of bipolar mania, and in 11 countries including the US for the treatment of bipolar depression. In May 2008 the U.S. Food and Drug Administration (FDA) approved SEROQUEL for the maintenance treatment of patients with bipolar I disorder, as adjunct to lithium or divalproex. A submission was recently made seeking similar approval in Europe, in line with previously announced clinical development plans.
SEROQUEL XR™ is approved in the US and 25 further countries for the treatment of schizophrenia in adult patients and for maintenance treatment of schizophrenia in adult patients. It was launched in the US in 2007 and earlier this year AstraZeneca announced the submission of regulatory applications in both the US and European Union for SEROQUEL XR in the treatment of manic episodes associated with bipolar disorder, and the treatment of depressive episodes associated with bipolar disorder. An sNDA for SEROQUEL XR seeking approval for the treatment of Major Depressive Disorder in the US was announced in February 2008 and a similar submission in Europe was announced in June 2008. SEROQUEL XR is not approved for these indications at this time and the applications remain under review by the regulatory authorities.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. In the United States, AstraZeneca is a $13.35 billion dollar healthcare business with 12,200 employees committed to improving people's lives. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
*Based on assumptions: (1) estimated number of prescriptions per patient based upon IMS APLD data; and (2) IMS Prescription data for SEROQUEL covering 13 major markets in which this data is available since the time of launch.
SEROQUEL XR is a trademark of the AstraZeneca group of companies.
1. Young AH, et al. Placebo-controlled study with acute and continuation phase of quetiapine in adults with bipolar depression (EMBOLDEN I). Presented at the European College of Neuropsychopharmacology Congress, Barcelona, Spain, 30 August-3 September, 2008.
2. McElroy S, et al. Placebo-controlled study with acute and continuation phase of quetiapine in adults with bipolar depression (EMBOLDEN II). Presented at the European College of Neuropsychopharmacology Congress, Barcelona, Spain, 30 August-3 September, 2008.
3. Nolen WA. Quetiapine or lithium vs. placebo in the maintenance treatment of bipolar disorder. Data presented at an AstraZeneca satellite symposium. Barcelona, Spain, 2 September, 2008.
4. Vieta E, et al. Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). J Affect Disord 2008;109:251-63.
5. Brecher M, et al. Quetiapine in the maintenance treatment of bipolar I disorder: combined data from two long-term phase III studies. Presented at the Conference of the International Society for Bipolar Disorders, Delhi, India, 27-30 January, 2008.