Schizophrenia
Conditions
Keywords
Schizophrenia
Brief summary
The primary purpose of this study is to evaluate the overall efficacy of aripiprazole intramuscular (IM) depot as acute treatment in subjects with schizophrenia. The secondary purpose is to evaluate the safety and tolerability of aripiprazole IM depot administered every 4 weeks for 12 weeks to adult subjects with schizophrenia.
Interventions
DRUGPlacebo
Matching Placebo
Sponsors
H. Lundbeck A/S
Otsuka America Pharmaceutical
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
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
* Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent. * Subjects with a diagnosis of schizophrenia for at least 1 year as defined by DSM-IV-TR criteria and confirmed by the MINI for Schizophrenia and Psychotic Disorders Studies. * Subjects with a stable living environment when not in hospital. * Subjects who would benefit from hospitalization or continued hospitalization for treatment of a current acute relapse of schizophrenia at trial entry. * Subjects who are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by meeting BOTH of the following at screening and baseline: * Currently experiencing an acute exacerbation of psychotic symptoms accompanied by significant deterioration in the subject's clinical and/or functional status from their baseline clinical presentation with a Positive and Negative Syndrome Scale (PANSS) Total Score ≥ 80 AND * Specific psychotic symptoms on the PANSS as measured by a score of \> 4 on each of the following items (possible scores of 1 to 7 for each item) * Conceptual disorganization (P2) * Hallucinatory behavior (P3) * Suspiciousness/persecution (P6) * Unusual thought content (G9) * Subjects who have received previous outpatient antipsychotic treatment at an adequate dose for an adequate duration and who showed a previous good response to such antipsychotic treatment (other than clozapine) in last 12 months. * Subjects with a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding current episode. * Subjects willing to discontinue all prohibited psychotropic medications to meet protocol required washouts prior to and during trial period. * BMI less ≤ 40 kg/m2 (morbid obesity) at screening. * Subjects who are able to provide written informed consent. * Ability to understand the nature of trial and follow protocol requirements.
Exclusion criteria
* Sexually active males of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 180 days after last dose of trial medication. Sexually active females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 150 days after last dose of trial medication. * Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP in this trial. * Subjects with improvement of ≥ 30% in total PANSS score between the screening and baseline assessments. - Subjects presenting with a first episode of schizophrenia - Subjects hospitalized for ≥ 30 days out of the last 90 days prior to screening visit. Subjects who have been hospitalized \> 5 days for current acute episode at the time of screening visit * Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment Subjects who have a history of response to clozapine treatment only. * Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder or mental retardation. * Subjects experiencing acute depressive symptoms within past 30 days that require treatment with an antidepressant. * Subjects with a significant risk of violent behavior; who represent a risk of committing suicide as indicated by any suicidal ideation within the last 1 month or any suicidal behaviors within the last year; or who present a serious risk of suicide. * Subjects with clinically significant tardive dyskinesia,. * Subjects with severe akathisia. * Subjects who have met DSM-IV-TR criteria for substance abuse with past 3 months prior to screening or dependence within past 6 months; including alcohol and benzodiazepines, but excluding caffeine and nicotine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Baseline to Week 10 | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). The primary statistical comparison was performed using the Mixed Model Repeated Measure (MMRM) approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Baseline to Week 10 | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). |
| Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Baseline to Week 10 | The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). |
| Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Baseline to Week 10 | The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: Considering your total experience with this particular population, how mentally ill is the patient at this time? Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants. |
| Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint. | Week 10 | The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: Considering your total experience with this particular population, how mentally ill is the patient at this time? Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants. |
| Responder Rate Based on PANSS Total Score. | Week 10 | Responder rate was defined as ≥30% reduction from Baseline in PANSS Total Score. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). |
| Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score. | Week 10 | The PSP was a validated clinician scale that measured personal and social functionining in 4 domains: socially useful activities eg, work and study), personal and social relationships, self-care, disturbing and aggressive behaviours. Impairement in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval and the study physician's judgement to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented varying degrees of disability (31 to 70) and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision. |
Countries
Croatia, Latvia, United States
Participant flow
Recruitment details
The trial was a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of aripiprazole IM (intramuscular) depot as treatment for an acute episode of schizophrenia in adult participants. The trial was conducted in 55 sites.
Pre-assignment details
This trial included a 13-Day Screening phase (which includes Washout from previous antipsychotics for 7 days and/or washout from other prohibited medications), a 12-Week acute treatment phase, and a 14 (±2) Day safety follow-up.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole IM Depot 400/300mg Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment). | 168 |
| Placebo Participants randomized to Placebo group received matching placebo. For 14 days beginning with the first injection, participants received concomitant oral placebo. | 172 |
| Total | 340 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 13 |
| Overall Study | Lack of Efficacy | 15 | 60 |
| Overall Study | Lost to Follow-up | 9 | 10 |
| Overall Study | Met Withdrawal Criteria | 7 | 6 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 35 | 17 |
Baseline characteristics
| Characteristic | Aripiprazole IM Depot 400/300mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.1 Years STANDARD_DEVIATION 11 | 42.7 Years STANDARD_DEVIATION 10.9 | 42.4 Years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 38 Participants | 33 Participants | 71 Participants |
| Sex: Female, Male Male | 130 Participants | 139 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 91 / 167 | 68 / 172 |
| serious Total, serious adverse events | 8 / 167 | 6 / 172 |
Outcome results
Primary
Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score.
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). The primary statistical comparison was performed using the Mixed Model Repeated Measure (MMRM) approach.
Time frame: Baseline to Week 10
Population: Efficacy sample was defined as the intent to treat (ITT) population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. Data of only 162 and 167 participants from aripiprazole and placebo groups were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 (N= 162, 167) | -8.9 Units on a scale | Standard Error 0.9 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 (N= 144, 157) | -15.2 Units on a scale | Standard Error 1.2 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 (N= 134, 140) | -19.0 Units on a scale | Standard Error 1.4 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 6 (N= 126, 117) | -21.5 Units on a scale | Standard Error 1.5 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 8 (N= 108, 96) | -23.7 Units on a scale | Standard Error 1.6 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 10 (N= 99, 81) | -26.8 Units on a scale | Standard Error 1.6 |
| Placebo | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 8 (N= 108, 96) | -9.7 Units on a scale | Standard Error 1.6 |
| Placebo | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 (N= 162, 167) | -5.0 Units on a scale | Standard Error 0.9 |
| Placebo | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 6 (N= 126, 117) | -10.3 Units on a scale | Standard Error 1.5 |
| Placebo | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 (N= 144, 157) | -8.3 Units on a scale | Standard Error 1.2 |
| Placebo | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 10 (N= 99, 81) | -11.7 Units on a scale | Standard Error 1.6 |
| Placebo | Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 (N= 134, 140) | -9.8 Units on a scale | Standard Error 1.3 |
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.p-value: 0.000595% CI: [-6.1, -1.7]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.p-value: <0.000195% CI: [-10, -4]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.p-value: <0.000195% CI: [-12.8, -5.6]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.p-value: <0.000195% CI: [-15, -7.3]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.p-value: <0.000195% CI: [-18.4, -9.6]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.p-value: <0.000195% CI: [-19.4, -10.8]Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score.
The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: Considering your total experience with this particular population, how mentally ill is the patient at this time? Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.
Time frame: Baseline to Week 10
Population: Efficacy sample was defined as the intent to treat (ITT) population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. Data of only 162 and 168 participants from aripiprazole and placebo groups were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 1 (N= 162, 168) | -0.4 Units on a scale | Standard Error 0.1 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 2 (N= 144, 157) | -0.8 Units on a scale | Standard Error 0.1 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 4 (N= 134, 140) | -1.0 Units on a scale | Standard Error 0.1 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 6 (N= 126, 117) | -1.2 Units on a scale | Standard Error 0.1 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 8 (N= 108, 96) | -1.3 Units on a scale | Standard Error 0.1 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 10 (N= 99, 81) | -1.4 Units on a scale | Standard Error 0.1 |
| Placebo | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 8 (N= 108, 96) | -0.6 Units on a scale | Standard Error 0.1 |
| Placebo | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 1 (N= 162, 168) | -0.2 Units on a scale | Standard Error 0.1 |
| Placebo | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 6 (N= 126, 117) | -0.5 Units on a scale | Standard Error 0.1 |
| Placebo | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 2 (N= 144, 157) | -0.4 Units on a scale | Standard Error 0.1 |
| Placebo | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 10 (N= 99, 81) | -0.6 Units on a scale | Standard Error 0.1 |
| Placebo | Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score. | Week 4 (N= 134, 140) | -0.4 Units on a scale | Standard Error 0.1 |
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: 0.000195% CI: [-0.4, -0.1]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-0.6, -0.2]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-0.7, -0.4]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-0.9, -0.5]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-0.9, -0.5]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-1.1, -0.6]Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score.
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Time frame: Baseline to Week 10
Population: Efficacy sample was defined as the intent to treat (ITT) population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. Data of only 162 and 167 participants from aripiprazole and placebo groups were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 1 (N= 162, 167) | -1.6 Units on a scale | Standard Error 0.2 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 2 (N= 144, 157) | -2.4 Units on a scale | Standard Error 0.3 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 4 (N= 134, 140) | -3.1 Units on a scale | Standard Error 0.4 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 6 (N= 126, 117) | -3.5 Units on a scale | Standard Error 0.4 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 8 (N= 108, 96) | -4.0 Units on a scale | Standard Error 0.4 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 10 (N= 99, 81) | -4.5 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 8 (N= 108, 96) | -1.4 Units on a scale | Standard Error 0.4 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 1 (N= 162, 167) | -0.7 Units on a scale | Standard Error 0.2 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 6 (N= 126, 117) | -1.3 Units on a scale | Standard Error 0.4 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 2 (N= 144, 157) | -1.2 Units on a scale | Standard Error 0.3 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 10 (N= 99, 81) | -1.6 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score. | Week 4 (N= 134, 140) | -1.3 Units on a scale | Standard Error 0.4 |
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: 0.002395% CI: [-1.6, -0.3]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: 0.003295% CI: [-2, -0.4]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: 0.000395% CI: [-2.7, -0.8]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-3.2, -1.3]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-3.7, -1.4]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-4.1, -1.6]Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score.
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Time frame: Baseline to Week 10
Population: Efficacy sample was defined as the intent to treat (ITT) population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. Data of only 162 and 167 participants from aripiprazole and placebo groups were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 1 (N= 162, 167) | -3.5 Units on a scale | Standard Error 0.3 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 2 (N= 144, 157) | -5.7 Units on a scale | Standard Error 0.4 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 4 (N= 134, 140) | -7.0 Units on a scale | Standard Error 0.5 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 6 (N= 126, 117) | -8.2 Units on a scale | Standard Error 0.5 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 8 (N= 108, 96) | -8.9 Units on a scale | Standard Error 0.5 |
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 10 (N= 99, 81) | -10.0 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 8 (N= 108, 96) | -4.1 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 1 (N= 162, 167) | -2.1 Units on a scale | Standard Error 0.3 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 6 (N= 126, 117) | -4.4 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 2 (N= 144, 157) | -3.4 Units on a scale | Standard Error 0.4 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 10 (N= 99, 81) | -4.9 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score. | Week 4 (N= 134, 140) | -3.9 Units on a scale | Standard Error 0.4 |
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-3.3, -1.3]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-4.3, -2]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: 0.000695% CI: [-2.1, -0.6]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-5.1, -2.6]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-6.2, -3.4]Mixed Models Analysis
Comparison: Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested.p-value: <0.000195% CI: [-6.4, -3.7]Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score.
The PSP was a validated clinician scale that measured personal and social functionining in 4 domains: socially useful activities eg, work and study), personal and social relationships, self-care, disturbing and aggressive behaviours. Impairement in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval and the study physician's judgement to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented varying degrees of disability (31 to 70) and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.
Time frame: Week 10
Population: Efficacy sample included participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had one Post-Baseline efficacy assessment. LOCF was used to impute the missing data with the recorded value obtained at the preceding visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole IM Depot 400/300mg | Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score. | 12.3 Units on a scale | Standard Error 1.2 |
| Placebo | Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score. | 5.2 Units on a scale | Standard Error 1.2 |
Comparison: Statistical analysis for Week 10.p-value: <0.000195% CI: [4.1, 10.1]ANCOVA
Secondary
Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint.
The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: Considering your total experience with this particular population, how mentally ill is the patient at this time? Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.
Time frame: Week 10
Population: Efficacy sample was defined as the ITT population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. LOCF was used to impute the missing data with the recorded value obtained at the preceding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole IM Depot 400/300mg | Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint. | 2.7 Units on a scale | Standard Deviation 1.2 |
| Placebo | Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint. | 3.7 Units on a scale | Standard Deviation 1.3 |
Comparison: Statistical analysis for Week 10. LOCF method were used in imputation of missing data.p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Responder Rate Based on PANSS Total Score.
Responder rate was defined as ≥30% reduction from Baseline in PANSS Total Score. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time frame: Week 10
Population: Efficacy sample was defined as the ITT population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. LOCF was used to impute the missing data with the recorded value obtained at the preceding visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole IM Depot 400/300mg | Responder Rate Based on PANSS Total Score. | 60 participants |
| Placebo | Responder Rate Based on PANSS Total Score. | 24 participants |
Comparison: Statistical analysis for Week 10. LOCF method were used in imputation of missing data.p-value: <0.000195% CI: [12.9, 32.4]Cochran-Mantel-Haenszel