Schizophrenia
Conditions
Keywords
Schizophrenia, Relapsed
Brief summary
This will be a multicenter, randomized, double-blind, placebo-controlled study designed to assess the tolerability, safety, and efficacy of OPC-34712 (0.25 to 6.0 mg) for the treatment of adult subjects hospitalized with an acute relapse of schizophrenia. Aripiprazole (10 to 20 mg) is included as a positive control to confirm the assay sensitivity of the study. A total of approximately 563 subjects will be screened at an estimated 75 sites worldwide in order to obtain approximately 450 randomized subjects.
Interventions
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects between 18 and 65 years of age, with a diagnosis of schizophrenia, as defined by DSM-IV-TR criteria 2. Subjects who have been recently hospitalized or who would benefit from hospitalization for an acute relapse of schizophrenia 3. Subjects experiencing an acute exacerbation of psychotic symptoms
Exclusion criteria
1. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug 2. Subjects with a current DSM-IV-TR Axis I diagnosis of: * Schizoaffective disorder * MDD * Bipolar disorder * Delirium, dementia, amnestic or other cognitive disorder * Borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder 3. Subjects presenting with a first episode of schizophrenia 4. Other protocol specific inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | Baseline to Week 6 | The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS total score is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | Baseline to Week 6 | The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. PANSS negative subscale score is the sum of the rating scores for the 7 negative scale items from the PANSS panel. The PANSS negative subscale score ranges from 7-49, with higher scores indicating more severe symptoms. |
| Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | Baseline to Week 6 | The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains. The rating is based on four main areas: (a) socially useful activities, including work and study; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The ratings are converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Ratings from 71-100 reflect only mild difficulties. Ratings from 31-70 reflect manifest disabilities of various degrees. Ratings from 1-30 reflect functioning so poor that intensive support or supervision is needed. |
| Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | Baseline to Week 6 | The severity of illness for each participant was rated using the CGI-S. To perform this assessment, 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 include the following: 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; 7=among the most extremely ill patients |
| Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | Baseline to Week 6 | The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms. |
| Response Rate at Week 6 | Week 6 | Response rate was defined as a reduction of ≥ 30% from baseline in PANSS Total Score; or a CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6 |
| Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | Baseline to Week 6 | Efficacy-related discontinuation rate was assessed |
| Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | Week 6 | The rater or investigator rated the particpant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at baseline prior to the first dose of double-blind study medication. Response choices included the following: 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. |
Countries
Bulgaria, Croatia, India, Philippines, Romania, Russia, Serbia, Slovakia, South Korea, Taiwan, Ukraine, United States
Participant flow
Recruitment details
459 participants recruited at 74 study centres in the United States, Asia and Europe. Participants not responding adequately to treatment at Week 4 visit could continue in study and receive open-label OPC-34712 (starting dose 2.5 mg/day with option for decrease to 2 mg/day or increase to 3 mg/day) until Week 6 at study physician's discretion.
Pre-assignment details
Partipants were randomized in a 1:2:2:2:2:1 ratio to the following groups: OPC-34712 0.25 mg arm, OPC-34712 low-dose, OPC-34712 mid-dose, OPC-34712 high-dose, Placebo, Aripiprazole. All other prohibited medications were discontinued at least 24 hours before the first dose of double-blind study medication.
Participants by arm
| Arm | Count |
|---|---|
| OPC-34712 0.25 mg 0.25 mg QD for 6 weeks | 42 |
| OPC-34712 Low-dose 1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment. | 89 |
| OPC-34712 Mid-dose 2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment. | 90 |
| OPC-34712 High-dose 5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment. | 93 |
| Aripiprazole 15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment. | 50 |
| Placebo Placebo QD for 6 weeks | 95 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 5 | 11 | 3 | 5 |
| Overall Study | Lack of Efficacy | 6 | 3 | 5 | 4 | 4 | 8 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Switched to Open Label Rescue | 7 | 17 | 11 | 11 | 4 | 15 |
| Overall Study | Withdrawal by Subject | 5 | 13 | 15 | 11 | 4 | 13 |
Baseline characteristics
| Characteristic | OPC-34712 0.25 mg | OPC-34712 Low-dose | OPC-34712 Mid-dose | OPC-34712 High-dose | Aripiprazole | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 40.4 Years STANDARD_DEVIATION 9.1 | 39.2 Years STANDARD_DEVIATION 10.3 | 37.4 Years STANDARD_DEVIATION 11.1 | 39.5 Years STANDARD_DEVIATION 11.1 | 40.8 Years STANDARD_DEVIATION 11 | 38.8 Years STANDARD_DEVIATION 11.4 | 39.1 Years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 15 Participants | 36 Participants | 30 Participants | 38 Participants | 16 Participants | 37 Participants | 172 Participants |
| Sex: Female, Male Male | 27 Participants | 53 Participants | 60 Participants | 55 Participants | 34 Participants | 58 Participants | 287 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 42 | 41 / 89 | 36 / 90 | 52 / 93 | 22 / 50 | 39 / 95 |
| serious Total, serious adverse events | 0 / 42 | 3 / 89 | 5 / 90 | 4 / 93 | 2 / 50 | 3 / 95 |
Outcome results
Primary
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase)
The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS total score is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.
Time frame: Baseline to Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The last observation carried forward (LOCF) method was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 0.25 mg | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | -9.76 Units on a scale | Standard Deviation 19.29 |
| OPC-34712 Low-dose | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | -18.73 Units on a scale | Standard Deviation 20.27 |
| OPC-34712 Mid-dose | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | -16.19 Units on a scale | Standard Deviation 18.55 |
| OPC-34712 High-dose | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | -18.25 Units on a scale | Standard Deviation 20.49 |
| Aripiprazole | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | -17.98 Units on a scale | Standard Deviation 21.32 |
| Placebo | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase) | -14.40 Units on a scale | Standard Deviation 20.13 |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.284695% CI: [-10.2, 0.82]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.606695% CI: [-6.96, 4.07]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.329395% CI: [-9.32, 1.59]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.226395% CI: [-2.89, 12.12]ANCOVA
p-value: 0.307495% CI: [-10.7, 3.38]ANCOVA
Secondary
Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase)
The severity of illness for each participant was rated using the CGI-S. To perform this assessment, 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 include the following: 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; 7=among the most extremely ill patients
Time frame: Baseline to Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 0.25 mg | Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | -0.39 Units on a scale | Standard Deviation 0.86 |
| OPC-34712 Low-dose | Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | -0.99 Units on a scale | Standard Deviation 1.29 |
| OPC-34712 Mid-dose | Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | -0.87 Units on a scale | Standard Deviation 1.11 |
| OPC-34712 High-dose | Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | -1.10 Units on a scale | Standard Deviation 1.24 |
| Aripiprazole | Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | -1.00 Units on a scale | Standard Deviation 1.21 |
| Placebo | Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase) | -0.82 Units on a scale | Standard Deviation 1.16 |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in CGI-S score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.068595% CI: [-0.03, 0.79]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.098995% CI: [-0.6, 0.05]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.800695% CI: [-0.37, 0.28]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.089895% CI: [-0.6, 0.04]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.285195% CI: [-0.59, 0.18]ANCOVA
Secondary
Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase)
The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. PANSS negative subscale score is the sum of the rating scores for the 7 negative scale items from the PANSS panel. The PANSS negative subscale score ranges from 7-49, with higher scores indicating more severe symptoms.
Time frame: Baseline to Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 0.25 mg | Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | -1.93 Units on a scale | Standard Deviation 5.24 |
| OPC-34712 Low-dose | Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | -3.61 Units on a scale | Standard Deviation 5.15 |
| OPC-34712 Mid-dose | Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | -3.84 Units on a scale | Standard Deviation 5.09 |
| OPC-34712 High-dose | Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | -3.99 Units on a scale | Standard Deviation 5.4 |
| Aripiprazole | Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | -3.00 Units on a scale | Standard Deviation 5.74 |
| Placebo | Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase) | -3.17 Units on a scale | Standard Deviation 4.88 |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS negative subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.289695% CI: [-0.86, 2.86]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS negative subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.370195% CI: [-1.94, 0.72]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS negative subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.607495% CI: [-1.69, 0.99]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS negative subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.277795% CI: [-2.05, 0.59]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS negative subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.861195% CI: [-1.9, 1.59]ANCOVA
Secondary
Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase)
The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms.
Time frame: Baseline to Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 0.25 mg | Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | -3.22 Units on a scale | Standard Deviation 5.26 |
| OPC-34712 Low-dose | Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | -5.97 Units on a scale | Standard Deviation 7.12 |
| OPC-34712 Mid-dose | Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | -4.94 Units on a scale | Standard Deviation 6.17 |
| OPC-34712 High-dose | Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | -5.98 Units on a scale | Standard Deviation 6.72 |
| Aripiprazole | Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | -6.60 Units on a scale | Standard Deviation 7.16 |
| Placebo | Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase) | -4.82 Units on a scale | Standard Deviation 6.34 |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS positive subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.180795% CI: [-0.75, 3.97]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS positive subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.131395% CI: [-3.24, 0.42]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS positive subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.887995% CI: [-1.96, 1.69]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS positive subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.176495% CI: [-3.05, 0.56]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS positive subscale score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.111195% CI: [-4, 0.42]ANCOVA
Secondary
Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase)
The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains. The rating is based on four main areas: (a) socially useful activities, including work and study; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The ratings are converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Ratings from 71-100 reflect only mild difficulties. Ratings from 31-70 reflect manifest disabilities of various degrees. Ratings from 1-30 reflect functioning so poor that intensive support or supervision is needed.
Time frame: Baseline to Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 0.25 mg | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | 4.54 Units on a scale | Standard Deviation 13.25 |
| OPC-34712 Low-dose | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | 11.36 Units on a scale | Standard Deviation 14.84 |
| OPC-34712 Mid-dose | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | 10.67 Units on a scale | Standard Deviation 15.21 |
| OPC-34712 High-dose | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | 12.17 Units on a scale | Standard Deviation 14.72 |
| Aripiprazole | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | 10.66 Units on a scale | Standard Deviation 13.13 |
| Placebo | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase) | 7.56 Units on a scale | Standard Deviation 14.9 |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PSP score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.372695% CI: [-7.57, 2.85]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PSP score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.066495% CI: [-0.26, 7.85]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.294495% CI: [-1.92, 6.32]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.059695% CI: [-0.16, 7.89]ANCOVA
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.181995% CI: [-1.53, 8.03]ANCOVA
Secondary
Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712
Efficacy-related discontinuation rate was assessed
Time frame: Baseline to Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-34712 0.25 mg | Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | 31 Percentage of participants |
| OPC-34712 Low-dose | Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | 22.5 Percentage of participants |
| OPC-34712 Mid-dose | Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | 17.8 Percentage of participants |
| OPC-34712 High-dose | Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | 16.1 Percentage of participants |
| Aripiprazole | Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | 16.0 Percentage of participants |
| Placebo | Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 | 24.2 Percentage of participants |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.85495% CI: [0.59, 1.88]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.449295% CI: [0.49, 1.38]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.185495% CI: [0.36, 1.23]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.094695% CI: [0.33, 1.1]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.213395% CI: [0.3, 1.34]Cochran-Mantel-Haenszel
Secondary
Mean Clinical Global Impression - Improvement (CGI-I) at Week 6
The rater or investigator rated the particpant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at baseline prior to the first dose of double-blind study medication. Response choices included the following: 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Time frame: Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 0.25 mg | Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | 3.66 Units on a scale | Standard Deviation 1.48 |
| OPC-34712 Low-dose | Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | 3.08 Units on a scale | Standard Deviation 1.58 |
| OPC-34712 Mid-dose | Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | 3.17 Units on a scale | Standard Deviation 1.45 |
| OPC-34712 High-dose | Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | 3.04 Units on a scale | Standard Deviation 1.5 |
| Aripiprazole | Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | 3.04 Units on a scale | Standard Deviation 1.52 |
| Placebo | Mean Clinical Global Impression - Improvement (CGI-I) at Week 6 | 3.34 Units on a scale | Standard Deviation 1.54 |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.4008Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.1117Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.2739Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.1045Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.1149Cochran-Mantel-Haenszel
Secondary
Response Rate at Week 6
Response rate was defined as a reduction of ≥ 30% from baseline in PANSS Total Score; or a CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6
Time frame: Week 6
Population: Consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. The LOCF method was used to impuite missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-34712 0.25 mg | Response Rate at Week 6 | 40.5 Percentage of participants |
| OPC-34712 Low-dose | Response Rate at Week 6 | 57.3 Percentage of participants |
| OPC-34712 Mid-dose | Response Rate at Week 6 | 46.7 Percentage of participants |
| OPC-34712 High-dose | Response Rate at Week 6 | 51.6 Percentage of participants |
| Aripiprazole | Response Rate at Week 6 | 60.0 Percentage of participants |
| Placebo | Response Rate at Week 6 | 49.5 Percentage of participants |
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.6295% CI: [0.57, 1.4]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.150195% CI: [0.95, 1.48]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.527195% CI: [0.66, 1.25]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-testp-value: 0.86795% CI: [0.78, 1.34]Cochran-Mantel-Haenszel
Comparison: Sample size was determined to achieve at least 80% power at alpha level of 0.0167 (two-sided) to detect a difference of -11.5 points in the mean change from baseline in PANSS Total Score at week 6 (LOCF) between an individual OPC-34712 treatment group (except the 0.25 mg QD fixed dose group) and placebo using a two-sided z-test.p-value: 0.389295% CI: [0.85, 1.56]Cochran-Mantel-Haenszel