A Long-term Trial of OPC-34712 in Patients With Schizophrenia

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01456897

Enrollment

282

Registered

2011-10-21

Start date

2011-10-31

Completion date

Unknown

Last updated

2019-12-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Brief summary

To investigate the safety and efficacy of long-term administration of OPC-34712 in patients with schizophrenia.

Interventions

DRUGOPC-34712

orally administered once daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients age 18 years or older (at time of informed consent) diagnosed with schizophrenia based on DSM-IV-TR diagnostic criteria * Outpatients who are receiving an oral antipsychotic treatment (other than clozapine), who are considered to require maintenance therapy using antipsychotics, and for whom monotherapy with OPC-34712 is considered feasible

Exclusion criteria

* Female patients who are breastfeeding or who have a positive pregnancy test (urine) result prior to receiving investigational medicinal product * Patients who are diagnosed with a disease other than schizophrenia (schizoaffective disorder, major depressive disorder, bipolar disorder, posttraumatic stress disorder, anxiety disorder, delirium, dementia, amnesia, or other cognitive disorder) based on current DSM-IV-TR Axis Ι criteria, or who are diagnosed with a personality disorder (borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial)

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Adverse Events	From Baseline up to 52 Weeks	A treatment-emergent adverse event (TEAE) is defined as an AE that started after start of investigational medicinal product (IMP) treatment.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)	The PANSS consisted of 3 subscales with 30 symptom constructs (positive subscale (7): delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/perseckion, and hostility; negative subscale (7): blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and conversation flow, stereotyped thinking and general psychopathology subscale (16): somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance). Severity was rated on 7-point scale with scores 1 (absence) & 7 (extremely severe). The PANSS Total score ranged from 7 (best possible outcome) to 210 (worst possible outcome).
Mean Change From Baseline in PANSS Positive Subscale Score	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)	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 PANSS positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).
Mean Change From Baseline in PANSS Negative Subscale Score	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)	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 PANSS 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 subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).
Mean Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S)	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)	Severity of illness for each participant was rated using the CGI-S, which was the secondary efficacy endpoint. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 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.
Mean Clinical Global Impression - Global Improvement(CGI-I)	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)	The efficacy of trial medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at Baseline prior to the first dose of study medication. 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.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
New Subjects Participants who had not previously participated in a brexpiprazole clinical study and who received 1-4 mg of daily treatment with open label brexpiprazole in this trial	184
Rollover Subjects Participants who rolled over from, and received blinded brexpiprazole or placebo in the randomized, double-blind, placebo-controlled Phase 2/3 efficacy studies (331-10-002); all received 1-4 mg of daily treatment with open label brexpiprazole in this trial	98
Total	282

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	19	22
Overall Study	Lack of Efficacy	4	11
Overall Study	Physician Decision	5	3
Overall Study	Protocol Violation	3	4
Overall Study	Withdrawal by Subject	44	17

Baseline characteristics

Characteristic	Rollover Subjects	New Subjects	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	29 Participants	29 Participants
Age, Categorical Between 18 and 65 years	98 Participants	155 Participants	253 Participants
Age, Continuous	42.5 years STANDARD_DEVIATION 12.5	45.5 years STANDARD_DEVIATION 14.7	44.4 years STANDARD_DEVIATION 14
Region of Enrollment Japan	98 participants	184 participants	282 participants
Sex: Female, Male Female	58 Participants	94 Participants	152 Participants
Sex: Female, Male Male	40 Participants	90 Participants	130 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 183	0 / 98
other Total, other adverse events	112 / 183	50 / 98
serious Total, serious adverse events	19 / 183	18 / 98

Outcome results

Primary

Percentage of Participants With Adverse Events

A treatment-emergent adverse event (TEAE) is defined as an AE that started after start of investigational medicinal product (IMP) treatment.

Time frame: From Baseline up to 52 Weeks

Population: Safety sample included those participants who had treated IMP.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
New Subjects	Percentage of Participants With Adverse Events	Treatment-Emergent Adverse Events (TEAE)	156 Participants
New Subjects	Percentage of Participants With Adverse Events	Severe Treatment-Emergent Adverse Event	8 Participants
New Subjects	Percentage of Participants With Adverse Events	Potentially Drug-related TEAE	95 Participants
New Subjects	Percentage of Participants With Adverse Events	Death	0 Participants
New Subjects	Percentage of Participants With Adverse Events	SAE	19 Participants
New Subjects	Percentage of Participants With Adverse Events	Discontinued Due to Adverse Events	20 Participants
Rollover Subjects	Percentage of Participants With Adverse Events	SAE	18 Participants
Rollover Subjects	Percentage of Participants With Adverse Events	Treatment-Emergent Adverse Events (TEAE)	79 Participants
Rollover Subjects	Percentage of Participants With Adverse Events	Death	0 Participants
Rollover Subjects	Percentage of Participants With Adverse Events	Severe Treatment-Emergent Adverse Event	7 Participants
Rollover Subjects	Percentage of Participants With Adverse Events	Discontinued Due to Adverse Events	23 Participants
Rollover Subjects	Percentage of Participants With Adverse Events	Potentially Drug-related TEAE	38 Participants

Secondary

Mean Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S)

Severity of illness for each participant was rated using the CGI-S, which was the secondary efficacy endpoint. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 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.