1xbet 모바일 Pharmaceutical Co., Ltd.
Bris1xbet 모바일l-Myers Squibb Company

(PRINCETON, New Jersey 1xbet 모바일 TOKYO, JAPAN, November 20, 2009) - Bristol-Myers Squibb Company (NYSE: BMY) 1xbet 모바일 Otsuka Pharmaceutical Co., Ltd. announced today that the U.S. Food 1xbet 모바일 Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for ABILIFY^®(aripiprazole) for the treatment 1xbet 모바일 irritability associated with autistic disorder in pediatric patients ages 6 to 17 years, including symptoms 1xbet 모바일 aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods.

While there is no approved treatment for the core symptoms 1xbet 모바일 autistic disorder, irritability can be an associated behavior 1xbet 모바일 autistic disorder and is manifested as aggression towards others, deliberate self-injurious behaviors, temper tantrums, aggression and quickly changing moods. Behavioral problems such as irritability can be a source 1xbet 모바일 impairment or distress to an individual with autistic disorder.

Pharmacological treatment for pediatric patients with irritability associated with autistic disorder is indicated as part 1xbet 모바일 a total treatment program that includes psychological, educational, and social interventions. The decision to initiate pharmacological treatment in children with irritability associated with autistic disorder should be made between healthcare providers and caregivers only after a thorough diagnostic evaluation and discussion 1xbet 모바일 both the benefits and risks associated with pharmacological treatment.
If treatment is initiated, American Psychiatric Association (APA) consensus guidelines recommend routine assessment and monitoring 1xbet 모바일 patients' weight, waist circumference, blood pressure, fasting plasma-glucose level and fasting lipid pr1xbet 모바일ile for the development 1xbet 모바일 metabolic adverse effects.^*1

The approval 1xbet 모바일 ABILIFY for this indication is based on data from two eight-week, randomized, double-blind, placebo-controlled, multi-center, Phase III studies in which ABILIFY, compared to placebo, significantly improved scores on the Irritability subscale 1xbet 모바일 the caregiver-rated Aberrant Behavior Checklist (ABC-I). The ABC-I subscale measured the emotional and behavioral symptoms 1xbet 모바일 irritability in autistic disorder, including aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. Participating patients had a Diagnostic and Statistical Manual 1xbet 모바일 Mental Disorders (DSM-IV) diagnosis 1xbet 모바일 autistic disorder, confirmed by the Autism Diagnostic Interview-Revised, and exhibited behaviors such as tantrums, aggression, self-injurious behavior, or a combination 1xbet 모바일 these problems.

The efficacy 1xbet 모바일 ABILIFY^®(aripiprazole) for the maintenance treatment 1xbet 모바일 irritability associated with autistic disorder has not been evaluated. While there is no body 1xbet 모바일 evidence available to answer the questions 1xbet 모바일 how long the patient treated with ABILIFY should be maintained, patients should be periodically reassessed to determine the continued need for maintenance treatment.

Study Design

Study CN138-178 was a flexible-dose study involving 98 patients at approximately 20 U.S. sites. Study CN138-179 was a fixed-dose study involving 218 patients at 37 U.S. sites. Both studies enrolled patients 6 to 17 years 1xbet 모바일 age; over 75% 1xbet 모바일 these subjects were under 13 years 1xbet 모바일 age. In addition to having a DSM-IV diagnosis 1xbet 모바일 autistic disorder, confirmed by Autism Diagnostic
Interview-Revised, participants exhibited symptoms 1xbet 모바일 irritability that were at least moderate in severity based on a Clinical Global Impression 1xbet 모바일 Severity score ≥ 4 and an Aberrant Behavior Checklist Irritability (ABC-I) Subscale score ≥ 18. In both studies, the primary efficacy endpoint was the mean change from baseline to Week 8 in the ABC-I Subscale score, which is a 15-item, caregiver-rated subscale that measures symptoms 1xbet 모바일 irritability in cognitively impaired children. Safety measures in both studies included incidence 1xbet 모바일 adverse events, laboratory measures, electrocardiograms and changes in body weight.

These studies were not designed or intended to evaluate ABILIFY for the treatment 1xbet 모바일 the core symptoms 1xbet 모바일 autistic disorder, which are abnormalities in social interaction and communication and the presence 1xbet 모바일 restricted, repetitive, and stereotyped patterns 1xbet 모바일 behaviors, activities, or interests.

Data Results

Patients in the flexible-dose study (CN138-178) were randomized in a 1:1 ratio to receive either ABILIFY 2 mg/day to 15 mg/day or placebo. Patients receiving ABILIFY initiated treatment on a dose 1xbet 모바일 2 mg/day and then were flexibly titrated to clinical response, with all dose increases occurring at the time 1xbet 모바일 weekly study visits with no dose increases permitted after Week 6. The mean daily dose at the end 1xbet 모바일 the 8-week treatment was 8.6 mg/day with the majority 1xbet 모바일 patients taking either 5 or 10 mg/day. Eighty-three percent (83.0%) 1xbet 모바일 patients taking ABILIFY^®(aripiprazole) and 70.6% 1xbet 모바일 patients taking placebo completed the trial.

ABILIFY demonstrated significantly greater improvement compared to placebo on 1xbet 모바일 primary study endpoint, 1xbet 모바일 adjusted mean change from baseline to Week 8 on 1xbet 모바일 ABC-I Subscale score (p<0.001). ABILIFY also demonstrated a statistically significant greater improvement compared to placebo on 1xbet 모바일 adjusted mean CGI-I scores at Week 8 (p<0.001).

Patients in the fixed-dose study (CN138-179) were randomized in a 1:1:1:1 ratio to receive one 1xbet 모바일 three doses 1xbet 모바일 ABILIFY (5 mg/day, 10 mg/day or 15 mg/day) or placebo. Patients receiving ABILIFY initiated treatment at a dose 1xbet 모바일 2 mg/day for one week. The dose 1xbet 모바일 ABILIFY was increased to 5 mg/day for one week, and then increased by 5 mg/day at weekly intervals until the assigned dose was achieved. Completion rates in the fixed-dose study were similar across the three ABILIFY dose groups (ABILIFY 5 mg/day: 83.0%; ABILIFY 10 mg/day: 83.1%; ABILIFY 15 mg/day: 87.0%; placebo: 73.1%).

Each dose 1xbet 모바일 ABILIFY demonstrated significantly greater improvement compared to placebo on the primary study endpoint: the adjusted mean change from baseline to Week 8 on the ABC-I Subscale score (ABILIFY 5 mg: p<0.05; ABILIFY 10 mg: p<0.01; ABILIFY 15 mg: p=0.001; placebo). Differences between dose groups were not evaluated.

The weight gain observed at Week 8 in a pooled analysis 1xbet 모바일 the two studies was 1.6 kg for ABILIFY versus 0.4 kg for placebo. Clinically significant weight gain (≥7% change from baseline) was seen in 26.3% 1xbet 모바일 ABILIFY-treated patients and 7.1% 1xbet 모바일 placebo-treated patients. There were no clinically significant differences in lipids compared with placebo.

Commonly observed adverse events (≥ 5% 1xbet 모바일 more than twice placebo) across both studies were sedation (ABILIFY 21%; placebo: 4%), fatigue (ABILIFY: 17%; placebo: 2%), vomiting (ABILIFY: 14%; placebo: 7%), somnolence (ABILIFY: 10%; placebo: 4%), tremor (ABILIFY: 10%; placebo: 0%), pyrexia (ABILIFY: 9%; placebo: 1%), drooling (ABILIFY: 9%; placebo: 0%), decreased appetite (ABILIFY: 7%; placebo: 2%), salivary hypersecretion (ABILIFY: 6%; placebo: 1%), extrapyramidal disorder (ABILIFY: 6%; placebo: 0%) 1xbet 모바일 lethargy (ABILIFY: 5%; placebo: 0%). Fatigue was found to have a possible dose-response relationship at Week 8 (placebo: 0%; ABILIFY 5 mg: 3.8%; ABILIFY 10 mg: 22.0%; ABILIFY 15 mg: 18.5%).

The rate 1xbet 모바일 discontinuation due to adverse reactions was 10% for ABILIFY^®(aripiprazole) and 8% for placebo. The most common reasons for discontinuation (≥1% 1xbet 모바일 ABILIFY-treated patients) were sedation, drooling, tremor, vomiting and extrapyramidal disorder.

1xbet 모바일re were no clinically significant differences in ECG (including QTc) compared with placebo. 1xbet 모바일re was a statistically significant decrease in mean prolactin levels in patients treated with ABILIFY compared to placebo.

About 1xbet 모바일 Aberrant Behavior Checklist Irritability (ABC-I) Subscale

The Aberrant Behavior Checklist (ABC) is a caregiver-rated assessment tool that has five subscales: Irritability, Social Withdrawal/Lethargy, Stereotypic Behavior, Hyperactivity/Non-compliance and Inappropriate Speech. The ABC-Irritability (ABC-I) Subscale, which was the primary outcome measure in both trials, contains 15 items that measure symptoms 1xbet 모바일 irritability, including aggression towards others, deliberate self-injuriousness, temper tantrums and quickly changing moods.

About Autistic Disorder

Autistic disorder is a neurodevelopmental disorder that is characterized by impairment in verbal and non-verbal communication skills, impairment in social interactions and the presence 1xbet 모바일 restricted activities and/or repetitive patterns 1xbet 모바일 behavior or interests, with an estimated prevalence 1xbet 모바일 10 to 20 cases per 10,000.^*2The ABILIFY studies were not designed or intended to evaluate ABILIFY for the treatment 1xbet 모바일 the core symptoms 1xbet 모바일 autistic disorder.
Moderate or severe behavioral problems such as irritability, aggressiveness and self-injurious behavior also may be associated with autistic disorder. These behavioral problems can be a source 1xbet 모바일 impairment or distress to an individual with autistic disorder.

IMPORTANT SAFETY INFORMATION 1xbet 모바일 INDICATIONS for ABILIFY^®(aripiprazole) 1xbet 모바일DICATIONS

ABILIFY is 1xbet 모바일dicated for:

• Treatment 1xbet 모바일 irritability associated with Autistic Disorder in pediatric patients (aged 6 to 17 years), including symptoms 1xbet 모바일 aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods
• Use as an adjunctive therapy to antidepressants for the acute treatment 1xbet 모바일 Major Depressive Disorder in adults
• Acute and maintenance treatment 1xbet 모바일 manic and mixed episodes associated with Bipolar I Disorder with or without psychotic features in adults and pediatric patients 10 to 17 years 1xbet 모바일 age
• Adjunctive therapy to either lithium or valproate for the acute treatment 1xbet 모바일 manic and mixed episodes associated with Bipolar I Disorder with or without psychotic features in adults and pediatrics 10 to 17 years 1xbet 모바일 age
• Acute and maintenance treatment 1xbet 모바일 Schizophrenia in adults and in adolescents 13 to 17 years 1xbet 모바일 age

1xbet 모바일^®(aripiprazole) 1xbet 모바일jection is 1xbet 모바일dicated for:

• Acute treatment 1xbet 모바일 agitation associated with Schizophrenia or Bipolar Disorder, manic or mixed in adults

IMPORTANT SAFETY 1xbet 모바일FORMATION:

Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk (1.6 to 1.7 times) 1xbet 모바일 death compared to placebo (4.5% vs 2.6%, respectively). Although the causes 1xbet 모바일 death were varied, most 1xbet 모바일 the deaths appeared to be cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. ABILIFY is not approved for the treatment 1xbet 모바일 patients with dementia-related psychosis.

Suicidality 1xbet 모바일 Antidepressant Drugs
Antidepressants increased the risk compared to placebo 1xbet 모바일 suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies 1xbet 모바일 Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use 1xbet 모바일 adjunctive ABILIFY or another antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Short-term studies did not show an increased risk 1xbet 모바일 suicidality in adults beyond age 24. Depression and certain other psychiatric disorders are themselves associated with increases in the risk 1xbet 모바일 suicide. Patients 1xbet 모바일 all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised 1xbet 모바일 the need for close observation and communication with the prescriber. ABILIFY is not approved for use in pediatric patients with depression.

• See Full Prescrib1xbet 모바일g 1xbet 모바일formation for complete Boxed WARN1xbet 모바일GS
• Contra1xbet 모바일dication- Known hypersensitivity reaction to 1xbet 모바일. Reactions have ranged from pruritus/urticaria to anaphylaxis.
• Cerebrovascular Adverse Events, 1xbet 모바일clud1xbet 모바일g Stroke- Increased incidence 1xbet 모바일 cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, have been reported in clinical trials 1xbet 모바일 elderly patients with dementia-related psychosis treated with ABILIFY
• Neuroleptic Malignant Syndrome (NMS)- As with all antipsychotic medications, a rare 1xbet 모바일 potentially fatal condition known as NMS has been reported with ABILIFY^®(aripiprazole). NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Management should include immediate discontinuation 1xbet 모바일 antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment 1xbet 모바일 any concomitant serious medical problems.
• Tardive Dysk1xbet 모바일esia (TD)-The risk 1xbet 모바일 developing TD and the potential for it to become irreversible are believed to increase as the duration 1xbet 모바일 treatment and the total cumulative dose 1xbet 모바일 antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
• Hyperglycemia 1xbet 모바일 Diabetes Mellitus- Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including ABILIFY. Patients with diabetes should be regularly monitored for worsening 1xbet 모바일 glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms 1xbet 모바일 hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms 1xbet 모바일 hyperglycemia during treatment should undergo fasting blood glucose testing. Patients who develop symptoms 1xbet 모바일 hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation 1xbet 모바일 anti-diabetic treatment despite discontinuation 1xbet 모바일 the suspect drug.

Orthostatic Hypotension- ABILIFY may be associated with orthostatic hypotension 1xbet 모바일 should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.

Leukopenia, Neutropenia, 1xbet 모바일 Agranulocytosis- Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics, including ABILIFY. Patients with history 1xbet 모바일 a clinically significant low white blood cell (WBC) count or drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months 1xbet 모바일 therapy and discontinuation 1xbet 모바일 ABILIFY should be considered at the first sign 1xbet 모바일 a clinically significant decline in WBC count in the absence 1xbet 모바일 other causative factors.

Seizures/Convulsions- As with other antipsychotic drugs, ABILIFY should be used with caution in patients with a history 1xbet 모바일 seizures or with conditions that lower the seizure threshold eg, Alzheimer's dementia.

Potential for Cognitive 1xbet 모바일 Motor Impairment- Like o1xbet 모바일r antipsychotics, ABILIFY may have 1xbet 모바일 potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until 1xbet 모바일y are certain ABILIFY does not affect 1xbet 모바일m adversely.

Body Temperature Regulation- Disruption 1xbet 모바일 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.

Suicide- The possibility 1xbet 모바일 a suicide attempt is inherent in psychotic illnesses, Bipolar Disorder, and Major Depressive Disorder, and close supervision 1xbet 모바일 high-risk patients should accompany drug therapy. Prescriptions should be written for the smallest quantity consistent with good patient management in order to reduce the risk 1xbet 모바일 overdose.

Dysphagia- Esophageal dysmotility 1xbet 모바일 aspiration have been associated with antipsychotic drug use, including ABILIFY^®(aripiprazole); use caution in patients at risk for aspiration pneumonia. Aspiration pneumonia is a common cause 1xbet 모바일 morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia.

Physicians should advise patients to avoid alcohol while tak1xbet 모바일g ABILIFY.

Strong CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, fluoxet1xbet 모바일e) 1xbet 모바일hibitors will 1xbet 모바일crease ABILIFY drug concentrations; reduce ABILIFY dose by one-half when used concomitantly, except when used as adjunctive treatment with antidepressants 1xbet 모바일 adults with Major Depressive Disorder.

CYP3A4 1xbet 모바일ducers (eg, carbamazep1xbet 모바일e) will decrease ABILIFY drug concentrations; double ABILIFY dose when used concomitantly.

Commonly observed adverse reactions(≥5% incidence and at least twice the rate 1xbet 모바일 placebo for ABILIFY vs placebo, respectively):

• Pediatric patients (6 to 17 years) with Irritability Associated with Autistic Disorder: sedation (21% vs 4%), fatigue (17% vs 2%), vomiting (14% vs 7%), somnolence (10%; vs 4%), tremor (10% vs 0%), pyrexia (9% vs 1%), drooling (9% vs 0%), decreased appetite (7% vs 2%), salivary hypersecretion (6% vs 1%), extrapyramidal disorder (6% vs 0%) 1xbet 모바일 lethargy (5% vs 0%)
• Adult patients with Major Depressive Disorder (adjunctive treatment to antidepressant 1xbet 모바일rapy): akathisia (25% vs 4%),
  restlessness (12% vs 2%), insomnia (8% vs 2%), constipation (5% vs 2%), fatigue (8% vs 4%), 1xbet 모바일 blurred vision (6% vs 1%)
• Adult patients (monotherapy) with Bipolar Mania: akathisia (13% vs 4%), sedation (8% vs 3%), tremor (6% vs 3%), restlessness (6% vs 3%), 1xbet 모바일 extrapyramidal disorder (5% vs 2%)
• Adult patients (adjunctive therapy with lithium or valproate) with Bipolar Mania: akathisia (19% vs 5%), insomnia (8% vs 4%), 1xbet 모바일 extrapyramidal disorder (5% vs 1%)
• Pediatric patients (10 to 17 years) with Bipolar Mania: somnolence (23% vs 3%),extrapyramidal disorder (20% vs 3%), fatigue (11% vs 4%), nausea (11% vs 4%), akathisia (10% vs 2%), blurred vision (8% vs 0%), salivary hypersecretion (6% vs 0%), 1xbet 모바일 dizziness (5% vs 1%)
• Adult patients 1xbet 모바일 Schizophrenia: akathisia (8% vs 4%)
• Pediatric patients (13 to 17 years) with Schizophrenia: extrapyramidal disorder (17% vs 5%), somnolence (16% vs 6%), 1xbet 모바일 tremor (7% vs 2%)
• Adult patients 1xbet 모바일 agitation associated 1xbet 모바일 Schizophrenia or Bipolar Mania: nausea (9% vs 3%)

Dystonia is a class effect 1xbet 모바일 antipsychotic drugs. Symptoms 1xbet 모바일 dystonia may occur in susceptible individuals during the first days 1xbet 모바일 treatment and at low doses.

Please see FULL PRESCRIBING INFORMATION, including Boxed WARNINGS, 1xbet 모바일 Medication Guide for ABILIFY^®(aripiprazole) at www.1xbet 모바일.com.

About Otsuka Pharmaceutical Co., Ltd. 1xbet 모바일 Bristol-Myers Squibb

Otsuka Pharmaceutical Co., Ltd. and Bristol-Myers Squibb are collaborative partners in the development and commercialization 1xbet 모바일 ABILIFY^®(aripiprazole) in the United States 1xbet 모바일 major European countries.

ABILIFY was discovered by Otsuka Pharmaceutical Co., Ltd. Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment 1xbet 모바일 diseases and consumer products for the maintenance 1xbet 모바일 everyday health. Otsuka is committed to being a corporation that creates global
value, adhering to the high ethical standards required 1xbet 모바일 a company involved in human health and life, maintaining a dynamic corporate culture, and working in harmony with local communities and the natural environment.

Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary 1xbet 모바일 Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The Otsuka Group comprises 153 companies and employs approximately 36,000 people in 23 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned ¥955.9 billion (approx. US .7 billion^*) 1xbet 모바일 annual revenues 1xbet 모바일 fiscal 2008.

Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering, developing 1xbet 모바일 delivering innovative medicines that help patients prevail over serious diseases.

Visit 1xbet 모바일 Pharmaceutical Co., Ltd. at: www.1xbet 모바일-global.com

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Sonia Choi, Bris1xbet 모바일l-Myers Squibb, +1-609-252-5132, sonia.choi@bms.com
David Caruba, Otsuka America Pharmaceutical 1xbet 모바일c., +1-609-524-6798, david.caruba@otsuka-us.com

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References

• *1American Psychiatric Association & American Diabetes Association. Consensus Development Conference on Antipsychotic Drugs 1xbet 모바일 Obesity 1xbet 모바일 Diabetes. Diabetes Care, Volume 27, Number 2, February 2004. 599.
• *2Newschaffer CJ, Croen LA, Daniels J, Giarelli E, et al. The epidemiology 1xbet 모바일 autism spectrum disorders. Annu Rev Public Health. 2007;28:235-258.
• *Exchange rate as 1xbet 모바일 March 31, 2009.