Schizophrenia
Conditions
Keywords
Schizophrenia
Brief summary
The primary objective of this study was to continue to provide aripiprazole intramuscular (IM) depot treatment (400 milligrams \[mg\] or 300 mg) to participants with schizophrenia completing the 52-week, open-label safety and tolerability Study 31-08-248. In addition, the secondary objective was to collect additional long-term safety data on aripiprazole IM depot treatment.
Detailed description
This was an open-label study that enrolled participants with schizophrenia who had completed the 52-week, open-label safety and tolerability Study 31-08-248 and continued to provide aripiprazole IM depot treatment. Participants received this treatment until aripiprazole IM Depot was commercially available in any dosage (including generic formulations) in the country where the study was being conducted or the commercial availability of aripiprazole IM Depot was terminated by the sponsor, or until the study completion date of 06 Dec 2018 was reached. Eligible participants entered this study at the end of treatment visit (Week 52) of Study 31-08-248. Participants continued to receive aripiprazole IM depot every month (study months were every 4 weeks, which were defined as 28 \[-2/+10\] days) as a continuation of their previous monthly dose in Study 31-08-248.
Interventions
DRUGAripiprazole
Aripiprazole IM depot - 300 mg or 400 mg
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants with a current diagnosis of schizophrenia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, who completed the open-label extension Study 248 (completed Study 248 study completion visit, Week 52). * Participants who, in the investigator's judgment, may benefit from continued participation in an aripiprazole IM Depot study. * The baseline visit for Study 270 (which is the Week 52 visit of Study 248) and the first injection for Study 270 must occur within 4 weeks (which was defined as 28 \[-2/+10\] days) of the last injection in Study 248. * Participants who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by an Independent Review Board/Independent Ethics Committee (IRB/IEC), prior to the initiation of any protocol-required procedures. * Participants able to understand the nature of the study and follow protocol requirements and who can read and understand the written word in order to complete patient-reported outcomes measures. * Outpatient status.
Exclusion criteria
* Participants with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic, or other cognitive disorders. * Participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. * Participants who currently meet DSM-IV-TR criteria for substance dependence, including alcohol and benzodiazepines, but excluding caffeine and nicotine. * Participants with a significant risk of violent behavior or a significant risk of committing suicide based on the investigator's judgment. * Participants who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones. * Participants with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia at screening. * Electroconvulsive therapy within 180 days prior to entry. * Any participant who requires or may need any other antipsychotic medications during the course of the study. * Aripiprazole IM Depot (including generic formulation) is commercially available in the participant's country. * Other protocol specific inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants Reporting Severe Treatment-Emergent Adverse Events (TEAE) | Baseline to Month 97 (+/- 3 days) | A TEAE was defined as an AE that started after start of investigational medicinal product (IMP) treatment or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption, or reduction of IMP. A severe AE was one that caused inability to work or perform normal daily activity. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change In Clinical Global Impression-Severity (CGI-S) of Illness Scale Score From Baseline To Last Visit | Baseline, Month 91 | The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. The Last Visit was defined as the last available post-baseline evaluation. A decrease in the CGI-S score indicated disease stability or improvement. |
Countries
Argentina, Australia, Bulgaria, Chile, Croatia, Estonia, Finland, Hungary, India, Malaysia, Mexico, Philippines, Poland, Puerto Rico, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, United States
Participant flow
Pre-assignment details
Participants with a current diagnosis of schizophrenia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, who completed the open-label extension Study 31-08-248 (NCT00731549) (completed Study 248 Study Completion visit, Week 52).
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole IM Depot Monthly dose of 400 milligrams (mg) or 300 mg aripiprazole intramuscular (IM) depot to adult participants with schizophrenia who completed aripiprazole IM depot treatment in Study 31-08-248. | 709 |
| Total | 709 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 39 |
| Overall Study | Death | 6 |
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Lost to Follow-up | 13 |
| Overall Study | Physician Decision | 27 |
| Overall Study | Protocol Deviation | 3 |
| Overall Study | Trial Termination by Sponsor | 6 |
| Overall Study | Withdrawal by Subject | 160 |
| Overall Study | Withdrawal Criteria Met | 19 |
Baseline characteristics
| Characteristic | Aripiprazole IM Depot |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 709 Participants |
| Age, Continuous Age (years) | 41.9 Years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 107 Participants |
| Race/Ethnicity, Customized Black or African American | 78 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 58 Participants |
| Race/Ethnicity, Customized White | 464 Participants |
| Sex: Female, Male Female | 295 Participants |
| Sex: Female, Male Male | 414 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 709 |
| other Total, other adverse events | 515 / 709 |
| serious Total, serious adverse events | 62 / 709 |
Outcome results
Primary
Number Of Participants Reporting Severe Treatment-Emergent Adverse Events (TEAE)
A TEAE was defined as an AE that started after start of investigational medicinal product (IMP) treatment or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption, or reduction of IMP. A severe AE was one that caused inability to work or perform normal daily activity. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline to Month 97 (+/- 3 days)
Population: The Safety Sample includes all participants who received at least 1 dose of open-label aripiprazole IM depot.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole IM Depot | Number Of Participants Reporting Severe Treatment-Emergent Adverse Events (TEAE) | 50 participants |
Secondary
Mean Change In Clinical Global Impression-Severity (CGI-S) of Illness Scale Score From Baseline To Last Visit
The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. The Last Visit was defined as the last available post-baseline evaluation. A decrease in the CGI-S score indicated disease stability or improvement.
Time frame: Baseline, Month 91
Population: The Efficacy Sample comprises those participants who entered the trial and had at least 1 post-baseline efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole IM Depot | Mean Change In Clinical Global Impression-Severity (CGI-S) of Illness Scale Score From Baseline To Last Visit | -0.14 units on a scale | Standard Deviation 0.69 |