Multicenter, Open-label, Safety and Tolerability Study | NCT01649557

NCT01649557

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

Label	Type	Description	Intervention Names
Open-label OPDC-34712	Experimental		Drug: OPC-34712

Name	Type	Description	Arm Group Labels	Other Names
OPC-34712	Drug	oral administered once daily	Open-label OPDC-34712

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs) During First 6 Weeks.	AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.	From Baseline up to 6 weeks
Number of Participants With AEs in 52-Week Enrollers.	AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A SAE was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A TEAE was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.	From Baseline up to 52 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit.	The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects who participated in 331-07-203 and who, in the opinion of the investigator, have the potential to benefit from continued administration of OPC-34712 for the treatment of schizophrenia.
Outpatient status at last visit of Study 331-07-203.

Exclusion Criteria:

Sexually active males who are not practicing two different methods of birth control during the study and for 90 days after the last dose of study medication or who will not remain abstinent during the study and for 90 days after the last dose, or sexually active females of childbearing potential who are not practicing two different methods of birth control during the study and for 30 days after the last dose of study medication or who will not remain abstinent during the study and for 30 days after the last dose. If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injection, birth control implant, condom, or sponge with spermicide.
Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving open-label OPC-34712.
Subjects who during the course of their participation in 331-07-203 were treated in violation of the protocol or who developed ANY exclusion criteria during the course of their participation.
Subjects who do not continue to meet all applicable inclusion/exclusion criteria for Protocol 331-07-203 at the last visit (ie, Week 6) of Protocol 331-07-203.
Subjects who represent a risk of committing suicide based on an answer of "Yes" to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS, or an answer of "Yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior) on the "Suicidal Behavior" portion of the C-SSRS. A subject who has had any suicidal ideation within the last 6 months, any suicidal behaviors within the last two years, or who in the clinical judgment of the investigator presents a serious risk of suicide should be excluded from the study.
Subjects who would be likely to require prohibited concomitant therapy during the study.
Any subject who, in the opinion of the investigator, should not participate in the study.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Otsuka Investigational Site		Little Rock	Arkansas	72211	United States
Otsuka Investigational 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.

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	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

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

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Prior Brexiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
BG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
BG002	Prior Apripiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
BG003	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

Participants with AEs

Title	Measurements
	OG00079 OG00119 OG0027

Participants with TEAEs

Primary

Number of Participants With AEs in 52-Week Enrollers.

AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A SAE was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A TEAE was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.

Those participants who received at least one dose of open-label brexpiprazole and who were enrolled in the 52-week study.

Posted

Number

Participants

From Baseline up to 52 weeks

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Secondary

Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Secondary

Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score.

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

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Secondary

Change From Baseline in Personal and Social Performance Scale (PSP) Total Score.

The PSP was a validated clinician-rated scale that measured personal and social functioning in four domains: socially useful activities (e.g, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment that determined the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented manifest disabilities of various degrees and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Median

Full Range

Units on a scale

Baseline, Week 1, 2, 6, 26, 52 and Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001

Secondary

Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score.

The efficacy of study medication was rated for each participant using the CGI-I. The investigator rated the participants total improvement whether or not it was due to the drug treatment. All responses were compared to the participants condition at Screening/Baseline (i.e, Week 6 visit of Protocol NCT00905307). Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Mean

Standard Deviation

Units on a scale

Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Secondary

Change From Baseline in PANSS Positive Subscale Score.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive symptom score ranges from 7-49, with higher scores indicating more severe symptoms.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Secondary

Change From Baseline in PANSS Negative Subscale Score.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In negative subscale the severity was rated for the following 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. The PANSS negative symptom score ranges from 7-49, with higher scores indicating more severe symptoms.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Secondary

Percentage of Participants With a Positive Response Rate.

Response rate was defined as a reduction of ≥ 30% from Baseline in PANSS total score or CGI-I score of 1 (very much improved) or 2 (much improved) at the Last Visit.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Number

Percentage of participants

Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG002	Prior Aripiprazole

Secondary

Percentage of Participants Who Discontinued Due to Lack of Efficacy.

Discontinuation rate for the participants discontinued due to lack of efficacy were examined.

The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Posted

Number

Percentage of participants.

Last Visit

ID	Title	Description
OG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
OG002	Prior Aripiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Prior Brexpiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	4	178	31	178
EG001	Prior Placebo	The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	6	41	10	41
EG002	Prior Aripiprazole	The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	1	23	4	23

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA V11.1	Non-systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected41 at risk EG0020 events0 affected23 at risk
Influenza	Infections and infestations	MedDRA V11.1	Non-systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected41 at risk EG0020 events0 affected23 at risk
Convulsion	Nervous system disorders	MedDRA V11.1	Non-systematic Assessment	EG0000 events0 affected178 at risk EG0011 events1 affected41 at risk EG0020 events0 affected23 at risk
Psychotic disorder	Psychiatric disorders	MedDRA V11.1	Non-systematic Assessment	EG0002 events2 affected178 at risk EG0011 events1 affected41 at risk EG0021 events1 affected23 at risk
Schizophrenia	Psychiatric disorders	MedDRA V11.1	Non-systematic Assessment	EG0002 events2 affected178 at risk EG0013 events3 affected41 at risk EG0020 events0 affected23 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Insomnia	Psychiatric disorders	MedDRA V11.1	Non-systematic Assessment	EG00010 affected178 at risk EG0013 affected41 at risk EG0020 affected23 at risk
Extrapyramidal disorder	Nervous system disorders	MedDRA V11.1	Non-systematic Assessment	EG0002 affected178 at risk EG0011 affected41 at risk EG0022 affected23 at risk
Headache	Nervous system disorders	MedDRA V11.1	Non-systematic Assessment	EG0006 affected178 at risk EG0015 affected41 at risk EG0020 affected23 at risk
Tremor	Nervous system disorders	MedDRA V11.1	Non-systematic Assessment	EG0009 affected178 at risk EG0011 affected41 at risk EG0020 affected23 at risk
Anxiety	Psychiatric disorders	MedDRA V11.1	Non-systematic Assessment	EG0005 affected178 at risk EG0010 affected41 at risk EG0022 affected23 at risk

ID	Term
D012559	Schizophrenia

The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders