FDA批准abilify用于治疗自闭症（6-17岁）的易怒

niuniuma

如题。想看英文的如下。

FDA Approves Bristol-Myers Squibb Company (BMY) (JOBS), Otsuka Pharmaceutical Co., Ltd.'s (JOBS) ABILIFY(R) (aripiprazole) for the Treatment of Irritability Associated with Autistic Disorder in Pediatric Patients (Ages 6 to 17 Years)
11/23/2009

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

While there is no approved treatment for the core symptoms of autistic disorder, irritability can be an associated behavior of 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 of impairment or distress to an individual with autistic disorder.

Pharmacological treatment for pediatric patients with irritability associated with autistic disorder is indicated as part of 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 of both the benefits and risks associated with pharmacological treatment. If treatment is initiated, American Psychiatric Association (APA) consensus guidelines recommend routine assessment and monitoring of patients’ weight, waist circumference, blood pressure, fasting plasma-glucose level and fasting lipid profile for the development of metabolic adverse effects.1

The approval of 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 of the caregiver-rated Aberrant Behavior Checklist (ABC-I). The ABC-I subscale measured the emotional and behavioral symptoms of 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 of Mental Disorders (DSM-IV) diagnosis of autistic disorder, confirmed by the Autism Diagnostic Interview-Revised, and exhibited behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these problems.

The efficacy of ABILIFY® (aripiprazole) for the maintenance treatment of irritability associated with autistic disorder has not been evaluated. While there is no body of evidence available to answer the questions of 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 of age; over 75% of these subjects were under 13 years of age. In addition to having a DSM-IV diagnosis of autistic disorder, confirmed by Autism Diagnostic Interview-Revised, participants exhibited symptoms of irritability that were at least moderate in severity based on a Clinical Global Impression of 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 of irritability in cognitively impaired children. Safety measures in both studies included incidence of adverse events, laboratory measures, electrocardiograms and changes in body weight.

These studies were not designed or intended to evaluate ABILIFY for the treatment of the core symptoms of autistic disorder, which are abnormalities in social interaction and communication and the presence of restricted, repetitive, and stereotyped patterns of 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 of 2 mg/day and then were flexibly titrated to clinical response, with all dose increases occurring at the time of weekly study visits with no dose increases permitted after Week 6. The mean daily dose at the end of the 8-week treatment was 8.6 mg/day with the majority of patients taking either 5 or 10 mg/day. Eighty-three percent (83.0%) of patients taking ABILIFY and 70.6% of patients taking placebo completed the trial.

ABILIFY® (aripiprazole) 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 (p<0.001). ABILIFY also demonstrated a statistically significant greater improvement compared to placebo on the 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 of three doses of ABILIFY (5 mg/day, 10 mg/day or 15 mg/day) or placebo. Patients receiving ABILIFY initiated treatment at a dose of 2 mg/day for one week. The dose of 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 of 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 of 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% of ABILIFY-treated patients and 7% of placebo-treated patients. There were no clinically significant differences in lipids compared with placebo.

Commonly observed adverse events (= 5% and 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%) and 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 of discontinuation due to adverse reactions was 10% for ABILIFY and 8% for placebo. The most common reasons for discontinuation (=1% of ABILIFY-treated patients) were sedation, drooling, tremor, vomiting and extrapyramidal disorder.

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

About the 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 of 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 of restricted activities and/or repetitive patterns of behavior or interests, with an estimated prevalence of 10 to 20 cases per 10,000.2 The ABILIFY studies were not designed or intended to evaluate ABILIFY for the treatment of the core symptoms of 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 of impairment or distress to an individual with autistic disorder.

IMPORTANT SAFETY INFORMATION and INDICATIONS for ABILIFY® (aripiprazole)

INDICATIONS

ABILIFY is indicated for:

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

ABILIFY® (aripiprazole) Injection is indicated for:

* Acute treatment of agitation associated with Schizophrenia or Bipolar Disorder, manic or mixed in adults

mrgood

稍微查阅一下，阿立哌唑(Aripiprazole)，抗精神病药，Bristol-Myers施贵宝及日本Otsuka公司研发，2002年上市，国内有仿制品。用于治疗精神分裂症，并非新药。

FDA批准的是用药适应症的延伸。可以用于伴有狂怒、攻击行为等自闭儿。而且，作为抗精神药物，使用十分严格，有很多条件。即使医生也不轻易对自闭儿用此药。家长更不要自行用此药！！！

只能说多了一种对付极重患儿的方法，但远非治疗大多数自闭患儿的曙光。

fsfz

阿立派唑我的孩子吃过，我认为不适用自闭症孩子，因为这个药物引起严重的失眠和鼻塞