Bristol-Myers Squibb Company And Otsuka Pharmaceutical Co., Ltd. Release: ABILIFY(R) (Aripiprazole) Demonstrated Efficacy As Maintenance Therapy In Adults With Bipolar I Disorder Following Treatment For A Recent Manic Or Mixed Episode
PRINCETON, N.J. and TOKYO, May 16 /PRNewswire-FirstCall/ -- Maintenance therapy with the Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co., Ltd. atypical antipsychotic ABILIFY(R) (aripiprazole) significantly delayed the time to relapse in adults with Bipolar I Disorder who had been stabilized and maintained on ABILIFY for at least six weeks, according to findings of a randomized, double-blind placebo-controlled study of patients with a recent manic or mixed episode published in the current issue of the Journal of Clinical Psychiatry.(1) These study results were based on rigorous criteria used to define stability for Bipolar I Disorder.
"These findings are important because Bipolar I Disorder is a lifelong episodic illness and an important goal of treatment is to prevent or delay recurrent mood symptoms," said lead investigator Paul E. Keck, Jr., M.D., professor of psychiatry and pharmacology and vice chairman for research, Department Of Psychiatry, University Of Cincinnati College Of Medicine. "Up to 40 percent of adults who respond to initial treatment have relapses within one year,(2),(3) emphasizing the need for maintenance treatment."
Bipolar I Disorder can be treated with antipsychotic medications.(4) ABILIFY is one of only two atypical antipsychotics indicated for maintenance therapy in Bipolar I Disorder. ABILIFY(R) (aripiprazole) is indicated for the treatment of acute manic and mixed episodes associated with Bipolar I Disorder, and for maintaining efficacy in adults with Bipolar I Disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least six weeks. Physicians who elect to use ABILIFY for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual.
Study Design and Findings
In the study, adults with Bipolar I Disorder who had recently been hospitalized and treated for a manic or mixed episode were initially stabilized with ABILIFY monotherapy (15 or 30 mg/day for 6-18 weeks). In the open-label stabilization phase, the adults in the study were required to maintain a total score of 10 or less on the Young Mania Rating Scale (YMRS) and 13 or less on the Montgomery-Asberg Depression Rating Scale (MADRS) for six consecutive weeks prior to randomization into the double-blind phase. In the double-blind phase, 161 adults were randomly assigned to ABILIFY or placebo and monitored for relapse. The primary endpoint was time to relapse for a manic, mixed, or depressive episode. Relapse was defined by a discontinuation from the study attributed to a lack of efficacy (indicated by hospital admission for a mood episode, or addition to or increase in psychotropic medication other than ABILIFY to treat affective symptoms).
Results from the study show: * ABILIFY was superior to placebo in delaying the time to relapse (p=0.020; hazard ratio=0.52). * Adults treated with ABILIFY experienced significantly fewer relapses than placebo: 25 percent vs 43 percent (p-value equals 0.013), respectively. * Adults treated with ABILIFY experienced fewer manic relapses than placebo: 8 percent vs 23 percent (p-value equals 0.009), respectively.
The majority of relapses were due to manic rather than depressive symptoms. There were insufficient data to know whether ABILIFY is effective in delaying the time to occurrence of depression in adults with Bipolar I Disorder.
More adults in the placebo group than in the ABILIFY(R) (aripiprazole) group (19.3 percent vs 10.4 percent, respectively) discontinued the study because of treatment-emergent adverse events. Adverse events among adults treated with ABILIFY with an incidence of 5 percent or more and at least twice the rate of placebo were: tremor (9.1%), akathisia (6.5%), vaginitis (6.4%), and pain in the extremities (5.2%). The safety profile demonstrated during this trial was generally consistent with data reported in other long-term placebo controlled trials of ABILIFY including changes in weight, prolactin, QTc and Extrapyramidal symptoms.(5)
About Bipolar Disorder(6)
Bipolar disorder, formerly called manic-depressive illness, is a condition that affects more than two million Americans. People who have this illness tend to experience extreme mood swings, along with other specific symptoms and behaviors. These mood swings or "episodes" can take three forms: manic episodes, depressive episodes, or "mixed" episodes. The symptoms of bipolar disorder are thought to be caused by an imbalance of key chemicals in the brain. Although there is no cure for bipolar disorder, medicine can play a key role in helping to manage symptoms and extreme mood swings.
In addition to its specific indications for Bipolar I Disorder, ABILIFY is indicated for the treatment of schizophrenia including maintaining stability in adults who had been symptomatically stable on other antipsychotic medications for periods of three months or longer and observed for relapse during a period of up to 26 weeks. Physicians who elect to use ABILIFY for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual. Since its initial approval in 2002, more than seven million prescriptions have been written in the United States.(7)
ABILIFY is available by prescription only. ABILIFY tablets are available in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg strengths. The effective dose range is 10-30 mg/day for schizophrenia patients, and 15 or 30 mg/day for Bipolar I Disorder patients. In addition to administration as a tablet, ABILIFY is available in a 1 mg/mL nonrefrigerated oral solution. The safety of doses of ABILIFY above 30 mg/day has not been evaluated in clinical trials.
ABILIFY is taken once daily with or without food.
It is important to talk to a healthcare provider for more information about ABILIFY(R) (aripiprazole). To learn more about ABILIFY and for FULL PRESCRIBING INFORMATION, including Boxed WARNING, please visit http://www.abilify.com.
IMPORTANT SAFETY INFORMATION for ABILIFY:
Increased Mortality in Elderly Patients With Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular or infectious in nature. ABILIFY is not approved for the treatment of patients with dementia-related psychosis (see Boxed WARNING).
ABILIFY is contraindicated in patients with a known hypersensitivity to the product.
As with all antipsychotic medications, including ABILIFY, a rare condition referred to as neuroleptic malignant syndrome (NMS) has been reported. As with all antipsychotic medications, prescribing should be consistent with the need to minimize the risk of tardive dyskinesia (TD).
Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported at an increased incidence in clinical trials of elderly patients with dementia-related psychosis treated with ABILIFY, including a significant dose response relationship in a fixed-dose trial. ABILIFY is not approved for the treatment of patients with dementia-related psychosis.
Hyperglycemia, including some serious cases ranging from ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Patients on ABILIFY should be appropriately tested before and monitored during treatment.
ABILIFY may be associated with orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.
As with other antipsychotic drugs, ABILIFY (aripiprazole) should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Like other antipsychotics, ABILIFY may have the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are certain ABILIFY does not affect them adversely.
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotics. Appropriate care is advised for patients who may exercise strenuously, be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or be subject to dehydration.
As antipsychotics have been associated with esophageal dysmotility and aspiration, ABILIFY(R) (aripiprazole) should be used cautiously in patients at risk for aspiration pneumonia.
As the possibility of a suicide attempt is inherent in psychotic illness and bipolar disorder, close supervision of high-risk patients should accompany drug therapy.
Prescriptions for ABILIFY should be written for the smallest quantity consistent with good patient management to reduce the risk of overdose.
Physicians should determine if a patient is pregnant or intends to become pregnant while taking ABILIFY. Patients should be advised not to breast-feed while taking ABILIFY.
Patients should be advised to avoid alcohol while taking ABILIFY.
Both CYP3A4 and CYP2D6 are responsible for ABILIFY metabolism. Agents that induce CYP3A4 (e.g., carbamazepine) could cause an increase in ABILIFY clearance and lower blood levels. Inhibitors of CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g., quinidine, fluoxetine, or paroxetine) can inhibit ABILIFY elimination and cause increased blood levels.
Commonly observed adverse events reported with ABILIFY in 3-week bipolar mania trials at a greater than or equal to 5% incidence for ABILIFY and at a rate at least twice the rate of placebo include, respectively, akathisia (15% vs. 4%), constipation (13% vs. 6%), and accidental injury (6% vs. 3%).
Treatment-emergent adverse events reported with ABILIFY in short-term trials at an incidence greater than or equal to 10% and greater than placebo, respectively, include headache (31% vs. 26%), agitation (25% vs. 24%), anxiety (20% vs. 17%), insomnia (20% vs. 15%), nausea (16% vs. 12%), dyspepsia (15% vs. 13%), somnolence (12% vs. 8%), akathisia (12% vs. 5%), lightheadedness (11% vs. 8%), vomiting (11% vs. 6%), and constipation (11% vs. 7%).
The adverse events reported in a 26-week, double-blind schizophrenia trial comparing ABILIFY (aripiprazole) and placebo were generally consistent with those reported in the short-term, placebo-controlled schizophrenia trials, except for a higher incidence of tremor: 9% for ABILIFY vs. 1% for placebo.
About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.
Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in the development and commercialization of ABILIFY(R) (aripiprazole) in the United States and major European countries.
ABILIFY was discovered by Otsuka Pharmaceutical Co., Ltd. Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a healthcare company with the mission statement: "Otsuka - people creating new products for better health worldwide." Otsuka researches, develops, manufactures and markets innovative, original products, focusing its core businesses on pharmaceutical products for the treatment of disease and consumer products for the maintenance of everyday health. The Otsuka Pharmaceutical Group comprises 81 companies and employs approximately 26,000 people in 16 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned US $6.2 billion in consolidated annual revenues in fiscal 2004.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
For more information and FULL PRESCRIBING INFORMATION including Boxed WARNING,
visit: www.abilify.com Visit Bristol-Myers Squibb at: www.bms.com Visit Otsuka Pharmaceutical Co., Ltd. at: www.otsuka-global.com (1) Keck PE Jr., Calabrese Jr., McQuade RD, Carson W, Carlson BX, Rollin LM, Marcus RN, Sanchez R, and the Aripiprazole Study Group. A placebo- controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psych 2006;67:626-37. (2) Gitlin MJ, Swendsen J, Heller TL, Hammen C: Relapse and impairment in bipolar disorder. Am J Psychiatry 1995; 152:1635-1640. (3) O'Connell RA, Mayo JA, Flatlow L, Cuthbertson B, O'Brien BE: Outcome of bipolar disorder on long-term treatment with lithium. Br J Psychiatry 1991;159:123-129. (4) American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (second edition). Executive summary of recommendations. Copyright (C) 2002 American Psychiatric Association. Also available at: http://www.psych.org/psych_pract/treatg/pg/bipolar_revisebook_1.cfm#parta-1. (5) Pigott TA, Carson WH, Saha AR, Torbeyns AF, Stock EG, Ingenito GG; Aripiprazole Study Group. Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo- controlled 26-week study. J Clin Psychiatry. 2003 Sep;64(9):1048-56. (6) What is Bipolar Disorder? Available by copying & pasting the following
URL into your web browser: http://www.abilify.com/abilify/channels/bipolar_content.jsp?BV_UseBVCookie=Yes &channelName=Bipolar%2fBP_Disorder&programName=&referrer=null
(7) IMS Auditrac NGPS: ABILIFY Total Monthly Retail Prescriptions: Data
Accessed 04/24/2006.Bristol-Myers Squibb Company; Otsuka Pharmaceutical Co., Ltd.
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