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

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01456897
• Collaborator: (none)
• Enrollment: 282
• Location: 1
• Arm: 1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: OPC-34712	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 282 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OPC-34712	Drug: OPC-34712; orally administered once daily

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Kanto Region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Kyoji Imaoka, Operating Officer, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01456897
• Other Study ID Numbers: 331-10-003; JapicCTI-111632
• First Posted: Oct 21, 2011
• Last Update Posted: Dec 30, 2019
• Last Verified: Oct 1, 2016

• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	184	98
COMPLETED	109	41
NOT COMPLETED	75	57

Baseline Characteristics

Arm/Group Title	New Subjects	Rollover Subjects	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	184	98	282
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	155 84.2%	98 100%	253 89.7%
>=65 years	29 15.8%	0 0%	29 10.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (14.7)	42.5 (12.5)	44.4 (14.0)
Sex: Female, Male (Count of Participants)
Female	94 51.1%	58 59.2%	152 53.9%
Male	90 48.9%	40 40.8%	130 46.1%
Region of Enrollment (participants) [Number]
Japan	184 100%	98 100%	282 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

Safety sample included those participants who had treated IMP.

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Measure Participants	183	98
Treatment-Emergent Adverse Events (TEAE)	156 84.8%	79 80.6%
Potentially Drug-related TEAE	95 51.6%	38 38.8%
Death	0 0%	0 0%
SAE	19 10.3%	18 18.4%
Severe Treatment-Emergent Adverse Event	8 4.3%	7 7.1%
Discontinued Due to Adverse Events	20 10.9%	23 23.5%

2. Secondary Outcome

Title	Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score
Description	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).
Time Frame	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)

Outcome Measure Data

Analysis Population Description

Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Measure Participants	182	97
Week24	-5.31 (9.00)	-7.20 (12.59)
Week52	-7.01 (10.56)	-9.44 (15.16)
Last Visit	-3.11 (12.76)	-2.58 (15.56)

3. Secondary Outcome

Title	Mean Change From Baseline in PANSS Positive Subscale Score
Description	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).
Time Frame	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)

Outcome Measure Data

Analysis Population Description

Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Measure Participants	182	97
WEEK24	-1.09 (2.27)	-1.53 (3.40)
WEEK52	-1.13 (2.73)	-1.61 (4.41)
Last Visit	-0.19 (3.96)	0.24 (4.83)

4. Secondary Outcome

Title	Mean Change From Baseline in PANSS Negative Subscale Score
Description	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).
Time Frame	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)

Outcome Measure Data

Analysis Population Description

Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Measure Participants	182	97
Week24	-1.64 (3.22)	-1.49 (3.84)
Week52	-2.27 (3.85)	-2.02 (4.47)
Last Visit	-1.43 (3.85)	-0.89 (3.92)

5. Secondary Outcome

Title	Mean Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S)
Description	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.
Time Frame	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)

Outcome Measure Data

Analysis Population Description

Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Measure Participants	182	97
Week24	-0.26 (0.71)	-0.20 (0.75)
Week52	-0.28 (0.67)	-0.15 (0.82)
Last Visit	-0.13 (0.81)	0.03 (0.92)

6. Secondary Outcome

Title	Mean Clinical Global Impression - Global Improvement(CGI-I)
Description	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.
Time Frame	From Baseline up to 52 Weeks including Week24, Week52, and Last Visit(LOCF)

Outcome Measure Data

Analysis Population Description

Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.

Arm/Group Title	New Subjects	Rollover Subjects
Arm/Group Description	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	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
Measure Participants	182	97
Week24	3.09 (0.94)	3.16 (0.90)
Week52	3.09 (0.91)	3.22 (0.99)
Last Visit	3.48 (1.22)	3.86 (1.27)

Adverse Events

Time Frame	Adverse events were monitored from signing of the informed consent form until follow-up for up to 30 days after the completion of the treatment period (52 weeks).
Adverse Event Reporting Description	Incidence of Non-Serious TEAE of at Least 5% in Any Group by System Organ Class and MedDRA Preferred Term
Arm/Group Title	New Subjects		Rollover Subjects
Arm/Group Description	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		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
All Cause Mortality
	New Subjects		Rollover Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/183 (0%)		0/98 (0%)
Serious Adverse Events
	New Subjects		Rollover Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/183 (10.4%)		18/98 (18.4%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/183 (0%)		1/98 (1%)
Infections and infestations
Meningitis aseptic	0/183 (0%)		1/98 (1%)
Injury, poisoning and procedural complications
Heat illness	0/183 (0%)		1/98 (1%)
Toxicity to various agents	0/183 (0%)		1/98 (1%)
Metabolism and nutrition disorders
Dehydration	1/183 (0.5%)		1/98 (1%)
Nervous system disorders
Akathisia	1/183 (0.5%)		1/98 (1%)
Extrapyramidal disorder	1/183 (0.5%)		0/98 (0%)
Psychiatric disorders
Schizophrenia	17/183 (9.3%)		13/98 (13.3%)
Other (Not Including Serious) Adverse Events
	New Subjects		Rollover Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/183 (61.2%)		50/98 (51%)
Gastrointestinal disorders
Diarrhoea	10/183 (5.5%)		3/98 (3.1%)
Infections and infestations
Nasopharyngitis	46/183 (25.1%)		19/98 (19.4%)
Investigations
Weight increased	9/183 (4.9%)		10/98 (10.2%)
Musculoskeletal and connective tissue disorders
Back pain	13/183 (7.1%)		4/98 (4.1%)
Nervous system disorders
Akathisia	15/183 (8.2%)		7/98 (7.1%)
Headache	19/183 (10.4%)		3/98 (3.1%)
Somnolence	13/183 (7.1%)		3/98 (3.1%)
Tremor	4/183 (2.2%)		8/98 (8.2%)
Psychiatric disorders
Schizophrenia	21/183 (11.5%)		13/98 (13.3%)
Insomnia	15/183 (8.2%)		2/98 (2%)
Skin and subcutaneous tissue disorders
Eczema	5/183 (2.7%)		6/98 (6.1%)

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.