Bipolar I Disorder
Conditions
Brief summary
To investigate the safety and efficacy of long-term administration of aripiprazole by performing extended administration of the treatment administered in the preceding multicenter, double-blind, placebo-controlled, parallel group-comparison trial of aripiprazole in patients with bipolar disorder experiencing a manic or mixed episode (Study 031-06-003, hereafter Study 003) in a double-blind manner to those patients who complete Study 003 and demonstrate drug efficacy.
Interventions
DRUGAripiprazole
oral, 24mg(4 tablets)/day
DRUGplacebo
oral, 0mg(4tablets)/day
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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. * Subjects 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. * Subjects 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 * Subjects who were enrolled in and have completed Study 003 and who meet the following criteria for demonstration of drug efficacy * Subjects demonstrating drug efficacy: * Those subjects who completed Study 003 whose score for CGI-BP Change From Preceding Phase (mania) at the time of evaluation on Day 21 of Study 003 (completion) was between 1 (Very much improved) and 3 (Minimally improved)
Exclusion criteria
* Subjects 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 * Subjects with psychotic symptoms that are clearly due to another general medical condition or direct physiological effects of a substance * Subjects who represent a significant risk of committing suicide * Subjects known to have a complication of allergy to aripiprazole or other quinolinone-skeleton compounds * Subjects with a complication of neuroleptic malignant syndrome * Subjects in a state of physical exhaustion accompanied by such conditions as dehydration or malnutrition * Subjects with a complication of paralytic ileus * Subjects with a complication of organic brain disorder or convulsive disorder, such as epilepsy * Subjects with a complication of diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale (YMRS) | Baseline (Day 1 of preceding study) , Day 154 or at discontinuation | Using LOCF datasets, descriptive statistics of actual values for changes of YMRS total scores from baseline (Day 1 of preceding study) to endpoint (Day 154) was calculated for each treatment group. 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) levated 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. YMRS ranges from 0 (best possible outcome) to 60 (worst possible outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness (Mania) | Baseline (Day 1 of preceding study), Day 154 or at discontinuation | Using LOCF datasets, descriptive statistics of actual values for change of CGI-BP severity of illness score (mania) from baseline (Day 1 of preceding study) to endpoint (Day 154) were calculated for each treatment group. CGI-BP severity of illness is a scale for overall evaluation of the severity of bipolar disorder; it comprises 3 components-mania, depression, and overall bipolar illness. CGI-BP severity of illness score (mania) ranges form 1 (normal, not ill) to 7 (very severely ill). |
Countries
China, Japan, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days. | 54 |
| Placebo Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days. | 42 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 5 |
| Overall Study | Change of residence or other commitments | 1 | 1 |
| Overall Study | Diabetic blood glucose level/ High HbA1c | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 7 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progression to depressive phase | 6 | 1 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Aripiprazole | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 41 Participants | 95 Participants |
| Age, Continuous | 38.7 years STANDARD_DEVIATION 11.95 | 37.8 years STANDARD_DEVIATION 11.67 | 38.3 years STANDARD_DEVIATION 11.78 |
| Region of Enrollment China | 9 participants | 9 participants | 18 participants |
| Region of Enrollment Indonesia | 5 participants | 2 participants | 7 participants |
| Region of Enrollment Japan | 22 participants | 10 participants | 32 participants |
| Region of Enrollment Malaysia | 4 participants | 6 participants | 10 participants |
| Region of Enrollment Philippines | 10 participants | 6 participants | 16 participants |
| Region of Enrollment Taiwan | 4 participants | 9 participants | 13 participants |
| Sex: Female, Male Female | 29 Participants | 24 Participants | 53 Participants |
| Sex: Female, Male Male | 25 Participants | 18 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 54 | 26 / 42 |
| serious Total, serious adverse events | 7 / 54 | 4 / 42 |
Outcome results
Primary
Young Mania Rating Scale (YMRS)
Using LOCF datasets, descriptive statistics of actual values for changes of YMRS total scores from baseline (Day 1 of preceding study) to endpoint (Day 154) was calculated for each treatment group. 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) levated 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. YMRS ranges from 0 (best possible outcome) to 60 (worst possible outcome).
Time frame: Baseline (Day 1 of preceding study) , Day 154 or at discontinuation
Population: FAS: The FAS consisted of subjects who had received at least one dose of investigational product and for whom the post-dosing efficacy parameter data had been obtained. Cases of GCP violation were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Young Mania Rating Scale (YMRS) | -22.6 scores on a scale | Standard Deviation 11.08 |
| Placebo | Young Mania Rating Scale (YMRS) | -15.4 scores on a scale | Standard Deviation 12.9 |
Secondary
Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness (Mania)
Using LOCF datasets, descriptive statistics of actual values for change of CGI-BP severity of illness score (mania) from baseline (Day 1 of preceding study) to endpoint (Day 154) were calculated for each treatment group. CGI-BP severity of illness is a scale for overall evaluation of the severity of bipolar disorder; it comprises 3 components-mania, depression, and overall bipolar illness. CGI-BP severity of illness score (mania) ranges form 1 (normal, not ill) to 7 (very severely ill).
Time frame: Baseline (Day 1 of preceding study), Day 154 or at discontinuation
Population: FAS: The FAS consisted of subjects who had received at least one dose of investigational product and for whom the post-dosing efficacy parameter data had been obtained. Cases of GCP violation were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness (Mania) | -2.9 scores on scale | Standard Deviation 1.45 |
| Placebo | Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness (Mania) | -1.9 scores on scale | Standard Deviation 1.7 |