Bipolar Disorder
Conditions
Brief summary
The purpose of this study is to look at the safety and effectiveness of aripiprazole (abilify) in children with bipolar disorder and to examine whether or not patients that respond to initial mood stabilization benefit from continued pharmacotherapy.
Detailed description
This outpatient study will be conducted in 3 phases. Phase 1: Patients meeting entry criteria will be treated with open label aripiprazole (APZ) in order to achieve therapeutic doses of this agent. The primary objective of this phase is to stabilize the patient's mood prior to randomization in phase 2. Adjunctive treatment of attention-deficit hyperactivity disorder (ADHD) will be permitted during this phase after week 6 of phase 1. In order to be entered into Phase 2, patients must be clinically stable based on a priori criteria (see below). The maximum allowable duration of Phase 1 will be 16 weeks. Only patients who have achieved syndromal remission (not just improvement) will be eligible for randomization into phase 2. Phase 2: Patients that achieve syndromal remission during Phase 1 will be randomized in a double-blind fashion to receive either ongoing APZ therapy or placebo therapy during Phase 2. Patients who are receiving co-administration of ADHD pharmacotherapy may continue with this during Phase 2. Patients will have an equal chance of being assigned to each of the 2 treatment arms. Randomization strata will be based on whether or not the subject is receiving ADHD pharmacotherapy and whether or not the subject is suffering from Bipolar 1 or 2 disorders. The maximum length of time a patient may remain in phase 2 will be 72 weeks. Youths who develop a major depressive episode, a manic, or mixed episode, or youths for whom continued enrollment in this phase of study is contraindicated (as determined by the patient, guardian, research team or study physician), will be withdrawn from phase 2. Youths who withdraw from phase 2 may enter Phase 3. Reason for removal from phase 2 will be documented. For those youths who successfully complete 72 weeks of participation in phase 2, trial participation will be ended. Those patients who complete phase 2 will receive follow up clinical care either at University Hospitals-Cleveland (UHC) or with a community-based physician. Phase 3: For youths who are withdrawn during phase 2, 8-weeks of open-label treatment with APZ will be available
Interventions
DRUGAripiprazole
dosing will occur at 2mg, 5mg, 7mg, 10 mg, 12mg, or 15 mg based on weight, side effects and efficacy
DRUGPlacebo
subjects in phase 2 will be randomized to active abilify or placebo
Sponsors
Bristol-Myers Squibb
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 9 Years
Healthy volunteers
Yes
Inclusion criteria
* Outpatients ages 4-9 years (inclusive) * Patients who are anticipated to have a Young Mania Rating Scale (Young et al. 1978) of 15 or higher at baseline * Meet DSM-IV criteria for bipolar disorder type 1 or 2, cyclothymia, or bipolar disorder not otherwise specified (BP NOS) based on the results of both a semi-structured diagnostic research assessment (K-SADS-PL supplemented with mood disorder sections from the WASH-U K-SADS) (Geller et al., 2001; Kaufman et al., 1997) and a clinical interview with a child and adolescent psychiatrist.
Exclusion criteria
* Patients who have a history of intolerance to APZ at doses of 0.1mg/kg/day * Patients who have experienced a manic episode with a documented APZ dose as monotherapy treatment of 0.2 mg/kg/day * Patients with an active neurological/medical disorder for which treatment with APZ would be contraindicated * Patients with clinical evidence of autistic disorder, Asperger's disorder, Rett's syndrome or other pervasive developmental disorders * Patients with clinical evidence of mental retardation * Patients who are known to be allergic or hypersensitive to aripiprazole * Patients who are unable to swallow pills/capsules * Patients for whom the need for hospitalization during the course of the study appears likely * Patients who have a general medical or neurological condition (including clinically significant abnormalities on screening laboratories) that may be considered to be the etiology of the patient's mood disorder * Patients who have a general medical or neurological condition for which treatment with an atypical antipsychotic would be contraindicated (e.g. tardive dyskinesia) * Patients who have a general medical or neurological condition that could interfere with the interpretation of clinical response to APZ treatment * Patients taking psychotropic agents (other than psychostimulants) within one week of baseline (2 weeks for fluoxetine; 3 days for psychostimulants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in Weeks to Discontinuation | up to 72 weeks | Time in weeks to discontinuation due to any reason, including mood event, adverse event, or other. |
Countries
United States
Participant flow
Recruitment details
Recruitment University Hospitals, Case Medical Center
Pre-assignment details
Open stabilization was initiated with aripiprazole at\ 0.1mg/kg upon phase 1, open stabilization entry, n+96. Of these, 60 subjects met priori response to advance to phase 2.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Abilify (Children with Symptoms of Mania Study) | 30 |
| Placebo Placebo (Children with Symptoms of Mania Study) | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 22 | 29 |
| Overall Study | Study nonadherence | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Aripiprazole | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 30 Participants | 30 Participants | 60 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 19 Participants | 23 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Time in Weeks to Discontinuation
Time in weeks to discontinuation due to any reason, including mood event, adverse event, or other.
Time frame: up to 72 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Aripiprazole | Time in Weeks to Discontinuation | 25.93 time in weeks to discontinuation |
| Placebo | Time in Weeks to Discontinuation | 3.00 time in weeks to discontinuation |