TOKYO, JAPAN & PRINCETON, NEW JERSEY, FEBRUARY 29 -- Otsuka Pharmaceutical Co., Ltd. and Bristol-Myers Squibb Company (NYSE: BMY) announced today that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application for ABILIFY (aripiprazole) for the acute treatment of manic and mixed episodes associated with Bipolar I Disorder, with or without psychotic features in pediatric patients (10 to 17 years old). ABILIFY has been approved for the acute and maintenance treatment of manic and mixed episodes associated with Bipolar I Disorder with or without psychotic features in adults since September 2004 and March 2005, respectively.
Pediatric bipolar illness is a serious condition, said Christoph Correll, M.D., Medical Director, Recognition and Prevention Program, The Zucker Hillside Hospital and Assistant Professor of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Glen Oaks, New York. The availability of an additional treatment option that can help guide decisions in managing Bipolar I Disorder in children and adolescents is welcome news.
The approval is based on results from a four-week, multicenter, randomized, double-blind, placebo-controlled study in pediatric patients (10 to 17 years old) with Bipolar I Disorder that demonstrated efficacy with ABILIFY compared to placebo on the primary efficacy endpoint, mean change from baseline to Week 4 on the Young-Mania Rating Scale (Y-MRS) Total Score.
We are pleased that the FDA has approved ABILIFY to treat pediatric patients aged 10 to 17 years suffering from Bipolar I Disorder, said Taro Iwamoto, Ph.D., Chief Executive Officer, President and Chief Operating Officer, Otsuka Pharmaceutical Development and Commercialization, Inc. The approval of this new indication for ABILIFY provides clinicians with expanded treatment options that can help address the therapeutic needs of this population.
We are committed to developing innovative new medicines to their fullest potential, said Elliott Sigal, M.D., Ph.D., Executive Vice President, Chief Scientific Officer and President, Research and Development, Bristol-Myers Squibb. Expanding the clinical use of an important therapy such as ABILIFY gives pediatric patients with Bipolar I Disorder and their caregivers a new treatment option in their fight against this serious disease.
Clinical Trial Design and Findings
These findings are from a four-week, multicenter, randomized, double-blind, placebo-controlled study, which evaluated the efficacy and safety of ABILIFY in 296 pediatric patients (10 to 17 years old) with a DSM-IV diagnosis of Bipolar I Disorder, manic or mixed episodes, with or without psychotic features. Diagnosis was made by a trained child and adolescent psychiatrist and confirmed by a separate diagnostic interview. This study was conducted on an outpatient basis with the possibility of inpatient hospitalization, as needed. This clinical trial was sponsored by Otsuka Pharmaceutical Co., Ltd. and its U.S. subsidiary, Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ) with enrollment at 54 U.S. centers.
After a screening period of up to four weeks, pediatric patients (10 to 17 years old) who scored greater than or equal to 20 on the Y-MRS* were randomly assigned to receive one of two fixed doses of ABILIFY [10 mg/day (n=98) or 30 mg/day (n=99)] or placebo (n=99). ABILIFY was initiated at a starting dose of 2 mg/day and titrated to the target dose of 10 mg/day or 30 mg/day.
The primary efficacy endpoint was the mean change in the Y-MRS Total Score from baseline to Week 4. Safety evaluations included incidence of adverse reactions, discontinuation due to adverse reactions, laboratory measures and body weight.
For the primary endpoint, both doses of ABILIFY demonstrated statistically significant improvement in symptoms when compared to placebo (p-value less than 0.0001) as measured by the mean change from baseline to endpoint (Week 4) on the Y-MRS Total Score. The efficacy of ABILIFY for the maintenance treatment of Bipolar I Disorder in the pediatric population has not been evaluated.
Approximately 80% of patients completed the four-week study (ABILIFY 10 mg: 86%; ABILIFY 30 mg: 78%; placebo: 77%). There was a low rate of discontinuation due to adverse reactions at Week 4 (ABILIFY: 7%; placebo: 2%).
During the study, the most commonly observed adverse reactions (greater than or equal to 5% in combined ABILIFY groups and at least twice the rate of placebo) associated with ABILIFY were: somnolence (ABILIFY: 23%; placebo: 3%), extrapyramidal disorder (ABILIFY: 20%; placebo: 3%), fatigue (ABILIFY: 11%; placebo: 4%), nausea (ABILIFY: 11%; placebo: 4%), akathisia (ABILIFY: 10%; placebo: 2%), blurred vision (ABILIFY: 8%; placebo: 0%), salivary hypersecretion (ABILIFY: 6%; placebo: 0%) and dizziness (ABILIFY: 5%; placebo: 1%). Four common adverse reactions had a possible dose-response relationship at Week 4: extrapyramidal disorder (ABILIFY 10 mg: 12.2%; ABILIFY 30 mg: 27.3%; placebo: 3.1%), somnolence (ABILIFY 10 mg: 19.4%; ABILIFY 30 mg: 26.3%; placebo: 3.1%), akathisia (ABILIFY 10 mg: 8.2%; ABILIFY 30 mg: 11.1%; placebo: 2.1%) and salivary hypersecretion (ABILIFY 10 mg: 3.1%; ABILIFY 30 mg: 8.1%; placebo: 0%). Children and adolescents might be more sensitive than adults in developing antipsychotic-related adverse events.(1)
In the study, weight gain greater than or equal to 7% change from baseline was seen in 3.2%, 9.4% and 3.3% for the ABILIFY 10 mg, ABILIFY 30 mg and placebo groups, respectively. The mean change from baseline to Week 4 in body weight was 0.6 kilograms (kg) for ABILIFY 10 mg, 0.9 kg for ABILIFY 30 mg and 0.5 kg for placebo.
In this study, ABILIFY demonstrated no clinically important differences on prolactin and the following metabolic parameters: triglyceride, HDL-C, LDL-C and total cholesterol. All treatment groups showed a reduction in mean serum prolactin levels at last visit relative to baseline.
|Contact: Debra Kaufmann|
Otsuka America Pharmaceutical, Inc.