Study to Evaluate the Efficacy, Safety, and Tolerability... | NCT00905307

NCT00905307

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	OPC-34712 0.25 mg arm	Drug: OPC-34712
2	Experimental	OPC-34712 low-dose arm	Drug: OPC-34712
3	Experimental	OPC-34712 mid-dose arm	Drug: OPC-34712
4	Experimental	OPC-34712 high-dose arm	Drug: OPC-34712
5	Placebo Comparator		Drug: Placebo
6	Active Comparator	Aripiprazole arm	Drug: Aripiprazole

Name	Type	Description	Arm Group Labels	Other Names
OPC-34712	Drug	oral, once daily	1 2 3 4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (Double Blind Phase)	The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS total score is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.	Baseline to Week 6

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 6 in PANSS Positive Subscale Score (Double Blind Phase)	The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms.

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Study Site		Little Rock	Arkansas	72211	United States
Study Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27188270	Derived	Kane JM, Skuban A, Hobart M, Ouyang J, Weiller E, Weiss C, Correll CU. Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia. Schizophr Res. 2016 Jul;174(1-3):93-98. doi: 10.1016/j.schres.2016.04.013. Epub 2016 May 14.
26250067	Derived	Citrome L. Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2015 Sep;69(9):978-97. doi: 10.1111/ijcp.12714. Epub 2015 Aug 6.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	OPC-34712 0.25 mg	0.25 mg once daily (QD) for 6 weeks
FG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks
BG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
BG002	OPC-34712 Mid-dose	2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
BG003	OPC-34712 High-dose	5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
BG004	Aripiprazole	15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
BG005	Placebo	Placebo QD for 6 weeks
BG006	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG000-9.76± 19.29 OG001-18.73± 20.27 OG002-16.19± 18.55 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG005	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.	ANCOVA	With treatment and trial center as main effects, and baseline value as covariate	0.2846	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.	Treatment difference	-4.70			2-Sided	95	-10.2	0.82				No

Secondary

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

The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS positive subscale score is the sum of the rating scores for the 7 positive scale items from the PANSS panel. The PANSS positive subscale score ranges from 7-49, with higher scores indicating more severe symptoms.

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks
OG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
OG002	OPC-34712 Mid-dose

Secondary

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

The PANSS consists of three subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating absence of symptoms and a score of 7 indicating extremely severe symptoms. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. PANSS negative subscale score is the sum of the rating scores for the 7 negative scale items from the PANSS panel. The PANSS negative subscale score ranges from 7-49, with higher scores indicating more severe symptoms.

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD
OG001	OPC-34712 Low-dose	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.

Secondary

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

The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains. The rating is based on four main areas: (a) socially useful activities, including work and study; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The ratings are converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Ratings from 71-100 reflect only mild difficulties. Ratings from 31-70 reflect manifest disabilities of various degrees. Ratings from 1-30 reflect functioning so poor that intensive support or supervision is needed.

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks
OG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.

Secondary

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

The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices include the following: 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD
OG001	OPC-34712 Low-dose	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.
OG002	OPC-34712 Mid-dose

Secondary

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

The rater or investigator rated the particpant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at baseline prior to the first dose of double-blind study medication. Response choices included the following: 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.

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.

Posted

Mean

Standard Deviation

Units on a scale

Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks
OG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
OG002	OPC-34712 Mid-dose	2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.

Secondary

Response Rate at Week 6

Response rate was defined as a reduction of ≥ 30% from baseline in PANSS Total Score; or a CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6

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.

Posted

Number

Percentage of participants

Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks
OG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
OG002	OPC-34712 Mid-dose	2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
OG003	OPC-34712 High-dose	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.

Secondary

Discontinuation Rate for Lack of Efficacy or Receipt of Open Label OPC-34712

Efficacy-related discontinuation rate was assessed

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.

Posted

Number

Percentage of participants

Baseline to Week 6

ID	Title	Description
OG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks
OG001	OPC-34712 Low-dose	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.
OG002	OPC-34712 Mid-dose	2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.
OG003	OPC-34712 High-dose	5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	OPC-34712 0.25 mg	0.25 mg QD for 6 weeks	0	42	20	42
EG001	OPC-34712 Low-dose	1.0 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	3	89	41	89
EG002	OPC-34712 Mid-dose	2.5 mg QD starting dose ± 0.5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	5	90	36	90
EG003	OPC-34712 High-dose	5.0 mg QD starting dose ± 1.0 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment.	4	93	52	93
EG004	Aripiprazole	15 mg QD starting dose ± 5 mg. After a minimum of 2 weeks of treatment, the physician could request a dose increase, if needed for efficacy, based on clinical judgment	2	50	22	50
EG005	Placebo	Placebo QD	3	95	39	95

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Death	General disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0020 affected90 at risk EG0031 affected93 at risk EG0040 affected50 at risk EG0050 affected95 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0011 affected89 at risk EG0020 affected90 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0021 affected90 at risk EG003
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0011 affected89 at risk EG0021 affected90 at risk EG003
Complex partial seizures	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0020 affected90 at risk EG003
Dizziness	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0021 affected90 at risk EG003
Anxiety	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0020 affected90 at risk EG003
Psychotic disorder	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0020 affected90 at risk EG003
Schizophrenia	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0011 affected89 at risk EG0021 affected90 at risk EG003
Schizophrenia, paranoid type	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0021 affected90 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0003 affected42 at risk EG0015 affected89 at risk EG0021 affected90 at risk EG0034 affected93 at risk EG0044 affected50 at risk EG0053 affected95 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0004 affected42 at risk EG0014 affected89 at risk EG0023 affected90 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0001 affected42 at risk EG0014 affected89 at risk EG0027 affected90 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0002 affected42 at risk EG0012 affected89 at risk EG0026 affected90 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA Version 11.1	Non-systematic Assessment	EG0001 affected42 at risk EG0010 affected89 at risk EG0022 affected90 at risk EG003
Weight increased	Investigations	MedDRA Version 11.1	Non-systematic Assessment	EG0001 affected42 at risk EG0016 affected89 at risk EG0029 affected90 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0003 affected42 at risk EG0012 affected89 at risk EG0023 affected90 at risk EG003
Akathisia	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0001 affected42 at risk EG0016 affected89 at risk EG0025 affected90 at risk EG003
Dizziness	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0014 affected89 at risk EG0022 affected90 at risk EG003
Extrapyramidal disorder	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0013 affected89 at risk EG0023 affected90 at risk EG003
Headache	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0006 affected42 at risk EG0018 affected89 at risk EG00213 affected90 at risk EG003
Somnolence	Nervous system disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0013 affected89 at risk EG0023 affected90 at risk EG003
Agitation	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0004 affected42 at risk EG0014 affected89 at risk EG0024 affected90 at risk EG003
Anxiety	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0005 affected42 at risk EG0017 affected89 at risk EG0026 affected90 at risk EG003
Restlessness	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0000 affected42 at risk EG0010 affected89 at risk EG0020 affected90 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0003 affected42 at risk EG0011 affected89 at risk EG0020 affected90 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0002 affected42 at risk EG0014 affected89 at risk EG0022 affected90 at risk EG003
Insomnia	Psychiatric disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0004 affected42 at risk EG00112 affected89 at risk EG0029 affected90 at risk EG003

ID	Term
D012559	Schizophrenia
D012008	Recurrence

Ancestor Terms

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000068180	Aripiprazole

Ancestor Terms

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

EG0040 affected50 at risk

EG0050 affected95 at risk

EG0040 affected50 at risk

EG0050 affected95 at risk

EG0041 affected50 at risk

EG0050 affected95 at risk

EG0041 affected50 at risk

EG0050 affected95 at risk

EG0040 affected50 at risk

EG0050 affected95 at risk

EG0040 affected50 at risk

EG0051 affected95 at risk

EG0040 affected50 at risk

EG0051 affected95 at risk

EG0040 affected50 at risk

EG0051 affected95 at risk

EG0040 affected50 at risk

EG0050 affected95 at risk

EG0041 affected50 at risk

EG0057 affected95 at risk

EG0041 affected50 at risk

EG0052 affected95 at risk

EG0043 affected50 at risk

EG0056 affected95 at risk

EG0040 affected50 at risk

EG0051 affected95 at risk

EG0043 affected50 at risk

EG0053 affected95 at risk

EG0040 affected50 at risk

EG0051 affected95 at risk

EG0042 affected50 at risk

EG0054 affected95 at risk

EG0041 affected50 at risk

EG0053 affected95 at risk

EG0042 affected50 at risk

EG0054 affected95 at risk

EG0043 affected50 at risk

EG00510 affected95 at risk

EG0040 affected50 at risk

EG0052 affected95 at risk

EG0045 affected50 at risk

EG0054 affected95 at risk

EG0045 affected50 at risk

EG00510 affected95 at risk

EG0043 affected50 at risk

EG0052 affected95 at risk

EG0040 affected50 at risk

EG0050 affected95 at risk

EG0041 affected50 at risk

EG0058 affected95 at risk

EG0044 affected50 at risk

EG00516 affected95 at risk