Antipsychotic Abilify for Treatment
of Acute Bipolar Mania
Supplemental new drug application filed with FDA
July 16, 2003
A Supplemental New Drug Application (sNDA) for
ABILIFY (aripiprazole) for the
treatment of acute mania in patients with bipolar disorder
has been submitted to the U.S. Food and Drug Administration (FDA). The FDA
approved
ABILIFY for the treatment of schizophrenia in November
2002.
The sNDA filing is based on efficacy and safety data from three 3-week
placebo-controlled studies and a 12-week active-controlled study in the
treatment of acute mania. The four trials examined the efficacy and safety of
ABILIFY at doses of 15-30 mg daily using the Young Mania Rating Scale (Y-MRS)
as the primary assessment tool.
Data from two of the three placebo-controlled studies showed ABILIFY to be
superior to placebo in symptom improvement. In these two pivotal trials,
improvement with ABILIFY as measured by the Y-MRS was statistically superior to
placebo by Day 4. In the third trial, ABILIFY demonstrated symptom improvement
comparable to that of the other studies; however, due to a high placebo
response rate (approximately 40%), ABILIFY did not show much of a statistical
difference from placebo.
In the active-controlled study, ABILIFY demonstrated comparable symptom
improvement (as measured by improvement in Y-MRS score) and a significantly
higher response rate compared to that of haloperidol (50% vs. 28%; p<0.001).
Response was defined as a greater than or equal to 50% decrease in scores on
the Y-MRS while remaining on therapy.
"The data in this sNDA submission examined ABILIFY in the treatment of
acute mania," said Joseph R. Calabrese, M.D., Professor of Psychiatry,
Case Western Reserve University School of Medicine, and Director, Mood
Disorders Program, University Hospitals of Cleveland. "ABILIFY is an
important therapeutic option for the treatment of schizophrenia, given its
proven efficacy, safety and tolerability profile. Evaluating the use of ABILIFY
in patients with acute mania is also critical, because additional treatment
options for this illness are needed."
Safety data from more than 1,141 patients enrolled in short and long-term
bipolar mania clinical trials was also included in the sNDA submission. In the
placebo-controlled bipolar trials, the incidence of clinically significant
weight gain, defined as >7% increase in body weight from baseline, was low
among both patients treated with ABILIFY (2.9%) and those receiving placebo
(2.4%) (see
weight gain from Abilify). Somnolence was reported by 14%
of patients treated with ABILIFY and 8% of patients receiving placebo.
In the placebo-controlled trials, discontinuations due to adverse events
with ABILIFY were similar to that of placebo (11% vs. 10%, respectively). The
discontinuation rate for adverse events with ABILIFY in the active-controlled
study was markedly lower than that of haloperidol (18% vs. 49%, respectively).
Common adverse events in the placebo-controlled studies (occurring at a rate of
greater than 5% and twice that of placebo) included akathisia, accidental
injury and extrapyramidal syndrome (EPS). These adverse events were generally
mild to moderate in severity and infrequently led to treatment discontinuation.
Akathisia describes a sustained, subjective sense of restlessness, and EPS
describes a range of muscular side effects, including tremors, muscle rigidity
and abnormal and involuntary muscle movements.
About Abilify
ABILIFY, the most recently approved treatment for schizophrenia in the
United States, Mexico, Brazil, Puerto Rico, Peru, and Australia, has been
prescribed for more than 150,000 people in the United States. ABILIFY is
available in 10 mg, 15 mg, 20 mg, and 30 mg tablets. When starting treatment,
some patients experience side effects such as headache, anxiety, insomnia,
nausea, vomiting, sleepiness, lightheadedness, restlessness, and constipation.
In short-term (4- and 6-week) placebo-controlled schizophrenia trials, there
was no statistical difference in the incidence of discontinuation due to
adverse events between patients treated with ABILIFY and placebo (7% and 9%,
respectively) or incidence of EPS (6% vs. 6%). In addition, studies showed that
ABILIFY was associated with a moderate difference in sedation compared to
placebo (11% vs. 8%, respectively), and did not cause significant QTc interval
changes. Bristol-Myers Squibb and Otsuka submitted a sNDA for the long-term
treatment of schizophrenia in December 2002.
SOURCE: Bristol-Myers Squibb press
release
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