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Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 and Aripiprazole for Treatment of Acute Schizophrenia (STEP 203)

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ClinicalTrials.gov Identifier: NCT00905307
Recruitment Status : Completed
First Posted : May 20, 2009
Results First Posted : September 3, 2015
Last Update Posted : October 20, 2015
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: OPC-34712
Drug: Placebo
Drug: Aripiprazole
Enrollment 459
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.

Arm/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High Dose Aripiprazole Placebo
Hide Arm/Group Description 0.25 mg once daily (QD) for 6 weeks 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. 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. 5.0 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. 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. Placebo QD for 6 weeks
Period Title: Overall Study
Started 42 89 90 93 50 95
Completed 20 52 53 56 34 53
Not Completed 22 37 37 37 16 42
Reason Not Completed
Switched to Open Label Rescue             7             17             11             11             4             15
Lost to Follow-up             0             0             0             0             1             1
Adverse Event             3             4             5             11             3             5
Withdrawal by Subject             5             13             15             11             4             13
Protocol Violation             1             0             1             0             0             0
Lack of Efficacy             6             3             5             4             4             8
Arm/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo Total
Hide Arm/Group Description 0.25 mg QD for 6 weeks 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. 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. 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. 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. Placebo QD for 6 weeks Total of all reporting groups
Overall Number of Baseline Participants 42 89 90 93 50 95 459
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants 89 participants 90 participants 93 participants 50 participants 95 participants 459 participants
40.4  (9.1) 39.2  (10.3) 37.4  (11.1) 39.5  (11.1) 40.8  (11) 38.8  (11.4) 39.1  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 89 participants 90 participants 93 participants 50 participants 95 participants 459 participants
Female
15
  35.7%
36
  40.4%
30
  33.3%
38
  40.9%
16
  32.0%
37
  38.9%
172
  37.5%
Male
27
  64.3%
53
  59.6%
60
  66.7%
55
  59.1%
34
  68.0%
58
  61.1%
287
  62.5%
1.Primary Outcome
Title Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD for 6 weeks
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
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
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
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
Placebo QD for 6 weeks
Overall Number of Participants Analyzed 41 88 90 92 50 93
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-9.76  (19.29) -18.73  (20.27) -16.19  (18.55) -18.25  (20.49) -17.98  (21.32) -14.40  (20.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2846
Comments The Hochberg procedure using two-sided alpha of 0.05 was applied to control the type I error rate at 0.05 level (two-sided) due to multiple comparisons.
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -4.70
Confidence Interval (2-Sided) 95%
-10.2 to 0.82
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6066
Comments The Hochberg procedure using two-sided alpha of 0.05 was applied to control the type I error rate at 0.05 level (two-sided) due to multiple comparisons.
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-6.96 to 4.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3293
Comments The Hochberg procedure using two-sided alpha of 0.05 was applied to control the type I error rate at 0.05 level (two-sided) due to multiple comparisons.
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.86
Confidence Interval (2-Sided) 95%
-9.32 to 1.59
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2263
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 4.62
Confidence Interval (2-Sided) 95%
-2.89 to 12.12
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3074
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.64
Confidence Interval (2-Sided) 95%
-10.7 to 3.38
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD for 6 weeks
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.
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.
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.
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.
Placebo QD for 6 weeks
Overall Number of Participants Analyzed 41 88 90 92 50 93
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-3.22  (5.26) -5.97  (7.12) -4.94  (6.17) -5.98  (6.72) -6.60  (7.16) -4.82  (6.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1807
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
-0.75 to 3.97
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1313
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.41
Confidence Interval (2-Sided) 95%
-3.24 to 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8879
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-1.96 to 1.69
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1764
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-3.05 to 0.56
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1111
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.79
Confidence Interval (2-Sided) 95%
-4.00 to 0.42
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD
1.0 mg QD starting dose ± 0.5 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
2.5 mg QD starting dose ± 0.5 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
5.0 mg QD starting dose ± 1.0 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
15 mg QD starting dose ± 5 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
Placebo QD
Overall Number of Participants Analyzed 42 89 90 93 50 95
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-1.93  (5.24) -3.61  (5.15) -3.84  (5.09) -3.99  (5.40) -3.00  (5.74) -3.17  (4.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2896
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
-0.86 to 2.86
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3701
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-1.94 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6074
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-1.69 to 0.99
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2777
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.73
Confidence Interval (2-Sided) 95%
-2.05 to 0.59
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8611
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-1.90 to 1.59
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD for 6 weeks
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.
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.
5.0 mg QD starting dose ± 1.0 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
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.
Placebo QD for 6 weeks
Overall Number of Participants Analyzed 39 86 84 90 50 90
Mean (Standard Deviation)
Unit of Measure: Units on a scale
4.54  (13.25) 11.36  (14.84) 10.67  (15.21) 12.17  (14.72) 10.66  (13.13) 7.56  (14.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3726
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.36
Confidence Interval (2-Sided) 95%
-7.57 to 2.85
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0664
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 3.80
Confidence Interval (2-Sided) 95%
-0.26 to 7.85
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2944
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.20
Confidence Interval (2-Sided) 95%
-1.92 to 6.32
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0596
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 3.86
Confidence Interval (2-Sided) 95%
-0.16 to 7.89
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1819
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 3.25
Confidence Interval (2-Sided) 95%
-1.53 to 8.03
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD
1.0 mg QD starting dose ± 0.5 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
2.5 mg QD starting dose ± 0.5 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
5.0 mg QD starting dose ± 1.0 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
15 mg QD starting dose ± 5 mg After a minimum of 2 weeks of treatment (eg, beginning at the Week 2 visit and at any subsequent visit where study medication was dispensed), the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
Placebo QD
Overall Number of Participants Analyzed 41 88 90 92 50 93
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.39  (0.86) -0.99  (1.29) -0.87  (1.11) -1.10  (1.24) -1.00  (1.21) -0.82  (1.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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-test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0685
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-0.03 to 0.79
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0989
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.60 to 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8006
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.37 to 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0898
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.60 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2851
Comments [Not Specified]
Method ANCOVA
Comments With treatment and trial center as main effects, and baseline value as covariate
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.59 to 0.18
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Clinical Global Impression - Improvement (CGI-I) at Week 6
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD for 6 weeks
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.
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.
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.
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.
Placebo QD for 6 weeks
Overall Number of Participants Analyzed 41 88 90 92 50 93
Mean (Standard Deviation)
Unit of Measure: Units on a scale
3.66  (1.48) 3.08  (1.58) 3.17  (1.45) 3.04  (1.50) 3.04  (1.52) 3.34  (1.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4008
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel (CMH) row mean scores differ test controlling for study center was applied to mean CGI-I score
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1117
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2739
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1045
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1149
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score
7.Secondary Outcome
Title Response Rate at Week 6
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD for 6 weeks
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.
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.
5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the investigator could request a dose increase, if needed for efficacy, based on clinical judgment.
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.
Placebo QD for 6 weeks
Overall Number of Participants Analyzed 42 89 90 93 50 95
Measure Type: Number
Unit of Measure: Percentage of participants
40.5 57.3 46.7 51.6 60.0 49.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6200
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center will be applied to the analysis of response rate
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.57 to 1.40
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1501
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center will be applied to the analysis of response rate
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.95 to 1.48
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5271
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center will be applied to the analysis of response rate
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.66 to 1.25
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8670
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center will be applied to the analysis of response rate
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.78 to 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3892
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center will be applied to the analysis of response rate
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.85 to 1.56
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712
Hide Description Efficacy-related discontinuation rate was assessed
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description:
0.25 mg QD for 6 weeks
1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physicna could request a dose increase, if needed for efficacy, based on clinical judgment.
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.
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
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.
Placebo QD
Overall Number of Participants Analyzed 42 89 90 93 50 95
Measure Type: Number
Unit of Measure: Percentage of participants
31 22.5 17.8 16.1 16.0 24.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OPC-34712 0.25 mg, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8540
Comments Derived using CMH test stratified by trial center.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.59 to 1.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OPC-34712 Low-dose, Placebo
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4492
Comments Derived using CMH test stratified by trial center.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.49 to 1.38
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OPC-34712 Mid-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1854
Comments Derived using CMH test stratified by trial center.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.36 to 1.23
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OPC-34712 High-dose, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0946
Comments Derived using CMH test stratified by trial center.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.33 to 1.10
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Aripiprazole, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2133
Comments Derived using CMH test stratified by trial center.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.63
Confidence Interval 95%
0.30 to 1.34
Estimation Comments [Not Specified]
Time Frame Adverse events (AEs) were recorded from the time of signing the informed consent, during the 6-week treatment period and up to 30 days after the last dose of study medication. The AEs presented are for the double blind phase.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Hide Arm/Group Description 0.25 mg QD for 6 weeks 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. 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. 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. 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 Placebo QD
All-Cause Mortality
OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/42 (0.00%)   3/89 (3.37%)   5/90 (5.56%)   4/93 (4.30%)   2/50 (4.00%)   3/95 (3.16%) 
General disorders             
Death * 1  0/42 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  1/93 (1.08%)  0/50 (0.00%)  0/95 (0.00%) 
Injury, poisoning and procedural complications             
Ankle fracture * 1  0/42 (0.00%)  1/89 (1.12%)  0/90 (0.00%)  0/93 (0.00%)  0/50 (0.00%)  0/95 (0.00%) 
Metabolism and nutrition disorders             
Hypoglycaemia * 1  0/42 (0.00%)  0/89 (0.00%)  1/90 (1.11%)  0/93 (0.00%)  0/50 (0.00%)  0/95 (0.00%) 
Musculoskeletal and connective tissue disorders             
Rhabdomyolysis * 1  0/42 (0.00%)  1/89 (1.12%)  1/90 (1.11%)  0/93 (0.00%)  1/50 (2.00%)  0/95 (0.00%) 
Nervous system disorders             
Complex partial seizures * 1  0/42 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  1/50 (2.00%)  0/95 (0.00%) 
Dizziness * 1  0/42 (0.00%)  0/89 (0.00%)  1/90 (1.11%)  0/93 (0.00%)  0/50 (0.00%)  0/95 (0.00%) 
Psychiatric disorders             
Anxiety * 1  0/42 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  0/50 (0.00%)  1/95 (1.05%) 
Psychotic disorder * 1  0/42 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  1/93 (1.08%)  0/50 (0.00%)  1/95 (1.05%) 
Schizophrenia * 1  0/42 (0.00%)  1/89 (1.12%)  1/90 (1.11%)  1/93 (1.08%)  0/50 (0.00%)  1/95 (1.05%) 
Schizophrenia, paranoid type * 1  0/42 (0.00%)  0/89 (0.00%)  1/90 (1.11%)  1/93 (1.08%)  0/50 (0.00%)  0/95 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OPC-34712 0.25 mg OPC-34712 Low-dose OPC-34712 Mid-dose OPC-34712 High-dose Aripiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/42 (47.62%)   41/89 (46.07%)   36/90 (40.00%)   52/93 (55.91%)   22/50 (44.00%)   39/95 (41.05%) 
Gastrointestinal disorders             
Diarrhoea * 1  3/42 (7.14%)  5/89 (5.62%)  1/90 (1.11%)  4/93 (4.30%)  4/50 (8.00%)  3/95 (3.16%) 
Dyspepsia * 1  4/42 (9.52%)  4/89 (4.49%)  3/90 (3.33%)  4/93 (4.30%)  1/50 (2.00%)  7/95 (7.37%) 
Nausea * 1  1/42 (2.38%)  4/89 (4.49%)  7/90 (7.78%)  6/93 (6.45%)  1/50 (2.00%)  2/95 (2.11%) 
Vomiting * 1  2/42 (4.76%)  2/89 (2.25%)  6/90 (6.67%)  2/93 (2.15%)  3/50 (6.00%)  6/95 (6.32%) 
Constipation * 1  2/42 (4.76%)  4/89 (4.49%)  2/90 (2.22%)  6/93 (6.45%)  1/50 (2.00%)  8/95 (8.42%) 
Investigations             
Blood creatine phosphokinase increased * 1  1/42 (2.38%)  0/89 (0.00%)  2/90 (2.22%)  5/93 (5.38%)  0/50 (0.00%)  1/95 (1.05%) 
Weight increased * 1  1/42 (2.38%)  6/89 (6.74%)  9/90 (10.00%)  6/93 (6.45%)  3/50 (6.00%)  3/95 (3.16%) 
Musculoskeletal and connective tissue disorders             
Back pain * 1  3/42 (7.14%)  2/89 (2.25%)  3/90 (3.33%)  3/93 (3.23%)  0/50 (0.00%)  1/95 (1.05%) 
Nervous system disorders             
Akathisia * 1  1/42 (2.38%)  6/89 (6.74%)  5/90 (5.56%)  14/93 (15.05%)  2/50 (4.00%)  4/95 (4.21%) 
Dizziness * 1  0/42 (0.00%)  4/89 (4.49%)  2/90 (2.22%)  5/93 (5.38%)  1/50 (2.00%)  3/95 (3.16%) 
Extrapyramidal disorder * 1  0/42 (0.00%)  3/89 (3.37%)  3/90 (3.33%)  6/93 (6.45%)  2/50 (4.00%)  4/95 (4.21%) 
Headache * 1  6/42 (14.29%)  8/89 (8.99%)  13/90 (14.44%)  7/93 (7.53%)  3/50 (6.00%)  10/95 (10.53%) 
Somnolence * 1  0/42 (0.00%)  3/89 (3.37%)  3/90 (3.33%)  5/93 (5.38%)  0/50 (0.00%)  2/95 (2.11%) 
Psychiatric disorders             
Agitation * 1  4/42 (9.52%)  4/89 (4.49%)  4/90 (4.44%)  7/93 (7.53%)  5/50 (10.00%)  4/95 (4.21%) 
Anxiety * 1  5/42 (11.90%)  7/89 (7.87%)  6/90 (6.67%)  10/93 (10.75%)  5/50 (10.00%)  10/95 (10.53%) 
Restlessness * 1  0/42 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  2/93 (2.15%)  3/50 (6.00%)  2/95 (2.11%) 
Insomnia * 1  4/42 (9.52%)  12/89 (13.48%)  9/90 (10.00%)  9/93 (9.68%)  4/50 (8.00%)  16/95 (16.84%) 
Respiratory, thoracic and mediastinal disorders             
Cough * 1  3/42 (7.14%)  1/89 (1.12%)  0/90 (0.00%)  1/93 (1.08%)  0/50 (0.00%)  0/95 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800-562-3924
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00905307     History of Changes
Other Study ID Numbers: 331-07-203
First Submitted: May 19, 2009
First Posted: May 20, 2009
Results First Submitted: August 4, 2015
Results First Posted: September 3, 2015
Last Update Posted: October 20, 2015