Study of Aripiprazole in adolescents with schizophrenia

May 24 2007

In a six-week study in adolescents (13-17 years old) with schizophrenia, the Otsuka Pharmaceutical Co., Ltd. and Bristol-Myers Squibb Company atypical antipsychotic aripiprazole demonstrated significant improvement compared to placebo on the primary efficacy endpoint, Positive and Negative Syndrome Scale (PANSS) Total Score.

In the findings first presented here at the 160th annual meeting of the American Psychiatric Association, approximately 85 percent of patients completed this six-week study. (1), (2)

"Data on the management of schizophrenia in adolescents are limited," said Robert Findling, M.D., Director of Child and Adolescent Psychiatry, University Hospitals Case Medical Center, Cleveland, Ohio. "The findings from this study contribute important new information about schizophrenia in adolescents."

The findings are from a six-week, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of aripiprazole in adolescents, 13-17 years-old, with a primary diagnosis of schizophrenia. This study, sponsored by Otsuka Pharmaceutical Co., Ltd. and its U.S. subsidiary, Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ) was conducted at 101 centers in 13 countries with 302 ethnically diverse adolescents. After a minimum three-day washout period without any antipsychotic treatment, adolescents were randomly assigned to receive one of two fixed doses of aripiprazole [10 mg/day (n=100) or 30 mg/day (n=102)] or placebo (n=100). Aripiprazole was started at 2 mg/day and titrated to the target dose. The primary efficacy endpoint was the mean change from baseline to endpoint (Week Six) in the PANSS Total Score. Secondary endpoints included the PANSS positive and negative subscales and the Clinical Global Impression of Improvement (CGI-I) scale. Important safety measures included incidence of adverse events, discontinuation from study due to adverse events, and laboratory measures.

Approximately 85 percent of 302 randomized patients completed this six-week study (83 percent of aripiprazole- and 90 percent of placebo-treated patients). Both doses of aripiprazole demonstrated improvement compared to placebo (p-value less than 0.05) in the mean change from baseline in PANSS Total Score at week six (aripiprazole 10 mg: -26.7; aripiprazole 30 mg: -28.6; placebo: -21.2).

The mean change from baseline to endpoint on PANSS Positive Subscale was: -7.6 for aripiprazole 10 mg (p-value less than 0.05), -8.1 for aripiprazole 30 mg (p-value less than 0.01), and -5.6 for placebo. The mean change from baseline to endpoint on PANSS Negative Subscale was: -6.9 for aripiprazole 10 mg (p-value less than 0.05), -6.6 for aripiprazole 30 mg, and -5.4 for placebo. Improvements were observed in CGI-I [aripiprazole 10 mg: 2.7 (p-value less than 0.05); aripiprazole 30 mg: 2.5 (p-value less than 0.01); placebo: 3.1].

In this study, the overall incidence of discontinuation due to adverse events was 4.3 percent for all treatment groups (5.4 percent of aripiprazole- and 2 percent of placebo-treated patients). The most common adverse events associated with aripiprazole (greater than 5 percent and at least twice the incidence compared to placebo) were extrapyramidal disorder (aripiprazole 10 mg: 13 percent; aripiprazole 30 mg: 21.6 percent; placebo: 5 percent), somnolence (aripiprazole 10 mg: 11 percent; aripiprazole 30 mg: 21.6 percent; placebo: 6 percent), and tremor (aripiprazole 10 mg: 2 percent; aripiprazole 30 mg: 11.8 percent; placebo: 2 percent).

No significant differences were found between aripiprazole and placebo on the Abnormal Involuntary Movement Scale (AIMS) or Barnes Akathisia Rating Scale (BARS). Significant differences between aripiprazole and placebo were observed from baseline (aripiprazole 10 mg: 0.5; aripiprazole 30 mg: 0.3; placebo: -0.3) on the Simpson-Angus Scale (SAS) which measures signs and symptoms of Parkinsonism.

In this 6-week study, the percentage of patients on aripiprazole with greater than or equal to 7 percent increase in baseline body weight was 4 percent for aripiprazole 10 mg, 5.2 percent for aripiprazole 30 mg, and 1 percent for placebo. The mean change from baseline in weight was zero for aripiprazole 10 mg group; 0.2 kg (about 0.4 lbs) for the aripiprazole 30 mg group, and -0.8 kilograms (kg), or about 1.8 lbs, for placebo group.

Average prolactin levels were decreased relative to baseline in all treatment groups (10 mg aripiprazole, -12 ng/mL; 30 mg aripiprazole, -17 ng/mL, placebo, -9 ng/mL).