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

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00905307
• Collaborator: (none)
• Enrollment: 459
• Locations: 73
• Arms: 6
• Duration (Months): 16
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: OPC-34712; Drug: Placebo; Drug: Aripiprazole	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 459 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, 6-Week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Oral OPC-34712 Once Daily and Aripiprazole Once Daily for Treatment of Hospitalized Adult Patients With Acute Schizophrenia
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 OPC-34712 0.25 mg arm	Drug: OPC-34712; oral, once daily
Experimental: 2 OPC-34712 low-dose arm	Drug: OPC-34712; oral, once daily
Experimental: 3 OPC-34712 mid-dose arm	Drug: OPC-34712; oral, once daily
Experimental: 4 OPC-34712 high-dose arm	Drug: OPC-34712; oral, once daily
Placebo Comparator: 5	Drug: Placebo; Placebo
Active Comparator: 6 Aripiprazole arm	Drug: Aripiprazole; oral, once daily

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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

5. 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.

6. 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

7. Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712 [Baseline to Week 6]

   Efficacy-related discontinuation rate was assessed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

1. Subjects presenting with a first episode of schizophrenia

2. Other protocol specific inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site	Little Rock	Arkansas	United States	72211
2	Study Site	Escondido	California	United States	92025
3	Study Site	Garden Grove	California	United States	92645
4	Study Site	Long Beach	California	United States	90813
5	Study Site	Oceanside	California	United States	92056
6	Study Site	Pasadena	California	United States	91107
7	Study Site	San Diego	California	United States	92102
8	Study Site	San Diego	California	United States	92123
9	Study Site	Santa Ana	California	United States	92701
10	Study Site	Washington	District of Columbia	United States	20016
11	Study Site	Bradenton	Florida	United States	34208
12	Study Site	Maitland	Florida	United States	32751
13	Study Site	St. Louis	Missouri	United States	63118
14	Study Site	Cedarhurst	New York	United States	11516
15	Study Site	Philadelphia	Pennsylvania	United States	19139
16	Study Site	Austin	Texas	United States	78756
17	Study Site	Burgas		Bulgaria	8000
18	Study Site	Kazanlak		Bulgaria	6100
19	Study Site	Pazardzhik		Bulgaria	4400
20	Study Site	Plovdiv		Bulgaria	4002
21	Study Site	Radnevo		Bulgaria	6260
22	Study Site	Ruse		Bulgaria	7003
23	Study Site	Rijeka		Croatia	51000
24	Study Site	Split		Croatia	21000
25	Study Site	Zagreb		Croatia	10090
26	Study Site	Vijaywada	Andh Prad	India	520002
27	Study Site	Visakhapatnam	Andh Prad	India	530017
28	Study Site	Ahmedabad	Gujarat	India	380015
29	Study Site	Bangalore	Karna	India	560010
30	Study Site	Mangalore	Karna	India	575001
31	Study Site	Mangalore	Karna	India	575018
32	Study Site	Pune	Mahara	India	411004
33	Study Site	Chennai	Tamilnadu	India	600003
34	Study Site	Varanasi	Uttar Prad	India	221005
35	Study Site	Busan		Korea, Republic of	613-735
36	Study Site	Chuncheon		Korea, Republic of	200-704
37	Study Site	Incheon		Korea, Republic of	400-711
38	Study Site	Incheon		Korea, Republic of	405-760
39	Study Site	Seoul		Korea, Republic of	143-711
40	Study Site	Cebu City 6000		Philippines
41	Study Site	Mandaluyong City 1553		Philippines
42	Study Site	Arad		Romania	310022
43	Study Site	Bucuresti		Romania	010825
44	Study Site (1)	Bucuresti		Romania	041914
45	Study Site (2)	Bucuresti		Romania	041914
46	Study Site (3)	Bucuresti		Romania	041914
47	Study Site	Cluj-Napoca		Romania	400012
48	Study Site	Oradea		Romania	410154
49	Study Site	Moscow Region		Russian Federation	141371
50	Study Site	Moscow		Russian Federation	113152
51	Study Site	Moscow		Russian Federation	115522
52	Study Site	St. Petersburg		Russian Federation	190121
53	Study Site	St. Petersburg		Russian Federation	193167
54	Study Site	St. Petersburg		Russian Federation	197341
55	Study Site (1)	Belgrade		Serbia	11000
56	Study Site (2)	Belgrade		Serbia	11000
57	Study Site	Kragujevac		Serbia	34000
58	Study Site	Novi Sad		Serbia	21000
59	Study Site	Bojnice		Slovakia	92701
60	Study Site	Bratislava		Slovakia	82606
61	Study Site	Liptovsky Mikulas		Slovakia	03123
62	Study Site	Rimavska Sobota		Slovakia	97912
63	Study Site	Zilina		Slovakia	01207
64	Study Site	Hualien Town		Taiwan	970
65	Study Site	Taipei		Taiwan	249
66	Study Site	Chernigiv		Ukraine	14005
67	Study Site	Dnipropetrovsk		Ukraine	49005
68	Study Site	Kherson,Vil. Stepanivka		Ukraine	73488
69	Study Site	Kyiv		Ukraine	02660
70	Study Site	Kyiv		Ukraine	04080
71	Study Site	Kyiv		Ukraine	04655
72	Study Site	Simferopol		Ukraine	95006
73	Study Site	Vinnitsia		Ukraine	21018

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT00905307
• Other Study ID Numbers: 331-07-203
• First Posted: May 20, 2009
• Last Update Posted: Oct 20, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Schizophrenia; Relapsed
• Additional relevant MeSH terms: Schizophrenia; Aripiprazole

Study Results

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	OPC-34712 0.25 mg	OPC-34712 Low-dose	OPC-34712 Mid-dose	OPC-34712 High-dose	Aripiprazole	Placebo	Total
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 Participants	42	89	90	93	50	95	459
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	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 (Count of Participants)
Female	15 35.7%	36 40.4%	30 33.3%	38 40.9%	16 32%	37 38.9%	172 37.5%
Male	27 64.3%	53 59.6%	60 66.7%	55 59.1%	34 68%	58 61.1%	287 62.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase)
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

Outcome Measure Data

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
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
Measure Participants	41	88	90	92	50	93
Mean (Standard Deviation) [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)

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.2263
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3074
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase)
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

Outcome Measure Data

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
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
Measure Participants	41	88	90	92	50	93
Mean (Standard Deviation) [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)

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
Statistical Test of Hypothesis	p-Value	0.1807
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.1313
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.8879
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -1.96 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.1764
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.1111
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 6 in PANSS Negative Subscale Score (Double Blind Phase)
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

Outcome Measure Data

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
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
Measure Participants	42	89	90	93	50	95
Mean (Standard Deviation) [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)

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
Statistical Test of Hypothesis	p-Value	0.2896
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.3701
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.6074
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.2777
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.8611
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) (Double Blind Phase)
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

Outcome Measure Data

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
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
Measure Participants	39	86	84	90	50	90
Mean (Standard Deviation) [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)

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
Statistical Test of Hypothesis	p-Value	0.3726
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0664
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.2944
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0596
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.1819
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score (Double Blind Phase)
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

Outcome Measure Data

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
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
Measure Participants	41	88	90	92	50	93
Mean (Standard Deviation) [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)

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
Statistical Test of Hypothesis	p-Value	0.0685
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0989
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.8006
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0898
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.2851
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Clinical Global Impression - Improvement (CGI-I) at Week 6
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

Outcome Measure Data

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
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
Measure Participants	41	88	90	92	50	93
Mean (Standard Deviation) [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)

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
Statistical Test of Hypothesis	p-Value	0.4008
	Comments
	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

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
Statistical Test of Hypothesis	p-Value	0.1117
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score

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
Statistical Test of Hypothesis	p-Value	0.2739
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score

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
Statistical Test of Hypothesis	p-Value	0.1045
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The CMH row mean scores differ test controlling for study center was applied to mean CGI-I score

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
Statistical Test of Hypothesis	p-Value	0.1149
	Comments
	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
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

Outcome Measure Data

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
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
Measure Participants	42	89	90	93	50	95
Number [Percentage of participants]	40.5 96.4%	57.3 64.4%	46.7 51.9%	51.6 55.5%	60.0 120%	49.5 52.1%

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
Statistical Test of Hypothesis	p-Value	0.6200
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.1501
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.5271
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.8670
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.3892
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712
Description	Efficacy-related discontinuation rate was assessed
Time Frame	Baseline to Week 6

Outcome Measure Data

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
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
Measure Participants	42	89	90	93	50	95
Number [Percentage of participants]	31 73.8%	22.5 25.3%	17.8 19.8%	16.1 17.3%	16.0 32%	24.2 25.5%

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
Statistical Test of Hypothesis	p-Value	0.8540
	Comments	Derived using CMH test stratified by trial center.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Relative risk
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.4492
	Comments	Derived using CMH test stratified by trial center.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.1854
	Comments	Derived using CMH test stratified by trial center.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.36 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0946
	Comments	Derived using CMH test stratified by trial center.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.33 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.2133
	Comments	Derived using CMH test stratified by trial center.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.63
	Confidence Interval	() 95%; 0.30 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

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.
Arm/Group Title	OPC-34712 0.25 mg		OPC-34712 Low-dose		OPC-34712 Mid-dose		OPC-34712 High-dose		Aripiprazole		Placebo
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		3/89 (3.4%)		5/90 (5.6%)		4/93 (4.3%)		2/50 (4%)		3/95 (3.2%)
General disorders
Death	0/42 (0%)		0/89 (0%)		0/90 (0%)		1/93 (1.1%)		0/50 (0%)		0/95 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/42 (0%)		1/89 (1.1%)		0/90 (0%)		0/93 (0%)		0/50 (0%)		0/95 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/42 (0%)		0/89 (0%)		1/90 (1.1%)		0/93 (0%)		0/50 (0%)		0/95 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/42 (0%)		1/89 (1.1%)		1/90 (1.1%)		0/93 (0%)		1/50 (2%)		0/95 (0%)
Nervous system disorders
Complex partial seizures	0/42 (0%)		0/89 (0%)		0/90 (0%)		0/93 (0%)		1/50 (2%)		0/95 (0%)
Dizziness	0/42 (0%)		0/89 (0%)		1/90 (1.1%)		0/93 (0%)		0/50 (0%)		0/95 (0%)
Psychiatric disorders
Anxiety	0/42 (0%)		0/89 (0%)		0/90 (0%)		0/93 (0%)		0/50 (0%)		1/95 (1.1%)
Psychotic disorder	0/42 (0%)		0/89 (0%)		0/90 (0%)		1/93 (1.1%)		0/50 (0%)		1/95 (1.1%)
Schizophrenia	0/42 (0%)		1/89 (1.1%)		1/90 (1.1%)		1/93 (1.1%)		0/50 (0%)		1/95 (1.1%)
Schizophrenia, paranoid type	0/42 (0%)		0/89 (0%)		1/90 (1.1%)		1/93 (1.1%)		0/50 (0%)		0/95 (0%)
Other (Not Including 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/42 (47.6%)		41/89 (46.1%)		36/90 (40%)		52/93 (55.9%)		22/50 (44%)		39/95 (41.1%)
Gastrointestinal disorders
Diarrhoea	3/42 (7.1%)		5/89 (5.6%)		1/90 (1.1%)		4/93 (4.3%)		4/50 (8%)		3/95 (3.2%)
Dyspepsia	4/42 (9.5%)		4/89 (4.5%)		3/90 (3.3%)		4/93 (4.3%)		1/50 (2%)		7/95 (7.4%)
Nausea	1/42 (2.4%)		4/89 (4.5%)		7/90 (7.8%)		6/93 (6.5%)		1/50 (2%)		2/95 (2.1%)
Vomiting	2/42 (4.8%)		2/89 (2.2%)		6/90 (6.7%)		2/93 (2.2%)		3/50 (6%)		6/95 (6.3%)
Constipation	2/42 (4.8%)		4/89 (4.5%)		2/90 (2.2%)		6/93 (6.5%)		1/50 (2%)		8/95 (8.4%)
Investigations
Blood creatine phosphokinase increased	1/42 (2.4%)		0/89 (0%)		2/90 (2.2%)		5/93 (5.4%)		0/50 (0%)		1/95 (1.1%)
Weight increased	1/42 (2.4%)		6/89 (6.7%)		9/90 (10%)		6/93 (6.5%)		3/50 (6%)		3/95 (3.2%)
Musculoskeletal and connective tissue disorders
Back pain	3/42 (7.1%)		2/89 (2.2%)		3/90 (3.3%)		3/93 (3.2%)		0/50 (0%)		1/95 (1.1%)
Nervous system disorders
Akathisia	1/42 (2.4%)		6/89 (6.7%)		5/90 (5.6%)		14/93 (15.1%)		2/50 (4%)		4/95 (4.2%)
Dizziness	0/42 (0%)		4/89 (4.5%)		2/90 (2.2%)		5/93 (5.4%)		1/50 (2%)		3/95 (3.2%)
Extrapyramidal disorder	0/42 (0%)		3/89 (3.4%)		3/90 (3.3%)		6/93 (6.5%)		2/50 (4%)		4/95 (4.2%)
Headache	6/42 (14.3%)		8/89 (9%)		13/90 (14.4%)		7/93 (7.5%)		3/50 (6%)		10/95 (10.5%)
Somnolence	0/42 (0%)		3/89 (3.4%)		3/90 (3.3%)		5/93 (5.4%)		0/50 (0%)		2/95 (2.1%)
Psychiatric disorders
Agitation	4/42 (9.5%)		4/89 (4.5%)		4/90 (4.4%)		7/93 (7.5%)		5/50 (10%)		4/95 (4.2%)
Anxiety	5/42 (11.9%)		7/89 (7.9%)		6/90 (6.7%)		10/93 (10.8%)		5/50 (10%)		10/95 (10.5%)
Restlessness	0/42 (0%)		0/89 (0%)		0/90 (0%)		2/93 (2.2%)		3/50 (6%)		2/95 (2.1%)
Insomnia	4/42 (9.5%)		12/89 (13.5%)		9/90 (10%)		9/93 (9.7%)		4/50 (8%)		16/95 (16.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/42 (7.1%)		1/89 (1.1%)		0/90 (0%)		1/93 (1.1%)		0/50 (0%)		0/95 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.