Bipolar I Disorder
Conditions
Brief summary
To assess the safety and efficacy of long-term administration of aripiprazole in combination with mood stabilizer (lithium or valproate) in an unblinded manner in patients with Bipolar I Disorder experiencing a manic or mixed episode
Interventions
DRUGAripiprazole
oral, 24mg/day
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Trial subjects will be men and women of age 18 or above and below the age of 65 who will not be turning 65 during the trial. * Patients have the ability to understand and to provide informed consent to the examination, observation, and evaluation processes specified in this protocol, and have signed the informed consent form based on a full understanding of the trial. * Patients who meet DSM-IV-TR criteria for manic or mixed episodes and have been diagnosed as having 296.4x Bipolar I Disorder in which the most recent episode was manic or 296.6x Bipolar I Disorder in which the most recent episode was mixed * Patients with a YMRS total score of 16 or more
Exclusion criteria
* Patients presenting with a clinical picture and/or history that is consistent with a DSM-IV-TR diagnosis of: * Delirium, dementia, amnestic disorder, or other cognitive disorders * Schizophrenia or other psychotic disorder * Personality disorder * Patients experiencing their first manic or mixed episode * Patients whose current manic episode has lasted for more than 4 weeks * Patients with psychotic symptoms that are clearly due to another general medical condition or direct physiological effects of a substance * Patients who have met DSM-IV-TR criteria for a substance-related disorder within 3 months (90 days) prior to informed consent (excluding caffeine- and nicotine-related disorders, but including abuse of benzodiazepines) * Patients who have received ECT treatment within 8 weeks prior to informed consent * Patients who are expected to require administration of ultrashort-acting or short-acting benzodiazepine receptor agonist hypnotics and antianxiety drugs (See (1) of 4.2.2) at doses exceeding the equivalent of 15 mg/day of diazepam (Only for those patients using such drugs) * Patients at significant risk of developing a severe adverse event. Patients who have a medical condition that would interfere with assessments of safety or efficacy during the course of the trial, or who have a history of such a condition. * Patients who have received any of the following treatments during the screening period * Reserpine * Levodopa, dopamine receptor stimulants * Monoamine oxidase inhibitors * Psychostimulants * Thyroid hormones, antithyroid drugs * Corticosteroids (other than topical preparations) * Adrenaline * All other investigational or unapproved agents * ECT * Light therapy * Patients judged to have a diabetic blood glucose level (judgment based on use of a self-monitoring blood glucose meter permissible), or patients whose HbA1c is 6.5% or higher * Patients with a history or a complication of diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale (YMRS) | Day 1 and Day 168 or time of discontinuation | Mean change from baseline (Day 1) to endpoint in the YMRS total score YMRS is composed of 11 evaluation items with 5 rating levels each. Items rated on a scale of 0 to 4 (comprising 5 rating levels of one point each) are 1) elevated mood, 2) increased motor activity/energy, 3) sexual interest, 4) sleep, 7) language-thought disorder, 10) appearance, and 11) insight. Items rated on a scale of 0 to 8 (comprising 5 rating levels of two points each) are 5) irritability, 6) speech (rate and amount), 8) content, and 9) disruptive-aggressive behavior. Total score range is 0 to 60, and the higher value represents worsen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Bipolar Version (CGI-BP) Sevirity of Illness Score (Mania) | Day 1 and Daty 168 or time of discontinuation | Mean change from baseline (Day 1) to endpoint in Clinical Global Impression -Bipolar Version (CGI-BP) severity of illness score (mania) The severity of manic symptoms on a scale of 1 (normal, not ill) to 7 (very severely ill) |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Twenty-four milligrams of aripiprazole (four 6-mg tablets) were administered orally once daily for 24 weeks (168 days) in an unblinded manner. The dose could be increased to a maximum of 30 mg/day (five 6-mg tablets). | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | change of residence or other commitments | 2 |
| Overall Study | does not meet inclusion criterion 1-3 | 4 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Aripiprazole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Age, Continuous | 40.4 years STANDARD_DEVIATION 10.89 |
| Region of Enrollment Japan | 40 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 41 |
| serious Total, serious adverse events | 4 / 41 |
Outcome results
Primary
Young Mania Rating Scale (YMRS)
Mean change from baseline (Day 1) to endpoint in the YMRS total score YMRS is composed of 11 evaluation items with 5 rating levels each. Items rated on a scale of 0 to 4 (comprising 5 rating levels of one point each) are 1) elevated mood, 2) increased motor activity/energy, 3) sexual interest, 4) sleep, 7) language-thought disorder, 10) appearance, and 11) insight. Items rated on a scale of 0 to 8 (comprising 5 rating levels of two points each) are 5) irritability, 6) speech (rate and amount), 8) content, and 9) disruptive-aggressive behavior. Total score range is 0 to 60, and the higher value represents worsen.
Time frame: Day 1 and Day 168 or time of discontinuation
Population: Results obtained from the LOCF dataset of 40 subjects of the Full Analysis Set (FAS) (excluding 1 subject whose post-dose data of efficacy endpoint were not available from the 41 treated subjects)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Young Mania Rating Scale (YMRS) | -18.8 scores on a scale | Standard Deviation 9.86 |
Secondary
Clinical Global Impression - Bipolar Version (CGI-BP) Sevirity of Illness Score (Mania)
Mean change from baseline (Day 1) to endpoint in Clinical Global Impression -Bipolar Version (CGI-BP) severity of illness score (mania) The severity of manic symptoms on a scale of 1 (normal, not ill) to 7 (very severely ill)
Time frame: Day 1 and Daty 168 or time of discontinuation
Population: Results obtained from the LOCF dataset of 40 subjects of the Full Analysis Set (FAS) (excluding 1 subject whose post-dose data of efficacy endpoint were not available from the 41 treated subjects)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Clinical Global Impression - Bipolar Version (CGI-BP) Sevirity of Illness Score (Mania) | -2.6 scores on a scale | Standard Deviation 1.5 |