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A Dose-finding Trial of OPC-34712 in Patients With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01451164
Recruitment Status : Completed
First Posted : October 13, 2011
Results First Posted : October 3, 2019
Last Update Posted : October 3, 2019
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: OPC-34712
Drug: Placebo
Enrollment 459
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description Brexpiprazole 1 mg tablet once daily for 6 weeks. Brexpiprazole 2 mg tablet once daily for 6 weeks. Brexpiprazole 4 mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks.
Period Title: Overall Study
Started 115 115 113 116
Completed 72 81 68 70
Not Completed 43 34 45 46
Reason Not Completed
Adverse Event             19             12             18             21
Withdrawal Criteria             1             1             1             1
Physician Decision             2             0             1             0
Withdrawal by Subject             14             11             16             17
Protocol Violation             0             1             0             0
Lack of Efficacy             7             9             9             7
Arm/Group Title Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo Total
Hide Arm/Group Description Brexpiprazole 1 mg tablet once daily for 6 weeks. Brexpiprazole 2 mg tablet once daily for 6 weeks. Brexpiprazole 4 mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 115 115 113 116 459
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 115 participants 113 participants 116 participants 459 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
115
 100.0%
115
 100.0%
113
 100.0%
116
 100.0%
459
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 115 participants 113 participants 116 participants 459 participants
44.7  (11.5) 43.3  (12.0) 44.1  (11.9) 45.0  (11.9) 44.3  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 115 participants 113 participants 116 participants 459 participants
Female
64
  55.7%
54
  47.0%
58
  51.3%
65
  56.0%
241
  52.5%
Male
51
  44.3%
61
  53.0%
55
  48.7%
51
  44.0%
218
  47.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 115 participants 115 participants 113 participants 116 participants 459 participants
115 115 113 116 459
1.Primary Outcome
Title Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was 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 ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Hide Outcome Measure Data
Hide 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 Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 112 113 109 113
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week1 Number Analyzed 110 participants 112 participants 109 participants 113 participants
-2.68  (1.04) -4.59  (1.03) -3.42  (1.05) -3.09  (1.03)
Week2 Number Analyzed 94 participants 104 participants 97 participants 98 participants
-5.07  (1.36) -7.93  (1.33) -6.80  (1.36) -4.54  (1.34)
Week3 Number Analyzed 86 participants 97 participants 88 participants 85 participants
-6.92  (1.60) -11.00  (1.55) -9.42  (1.59) -6.00  (1.58)
Week4 Number Analyzed 80 participants 92 participants 82 participants 77 participants
-8.40  (1.81) -12.35  (1.74) -11.21  (1.80) -5.67  (1.80)
Week5 Number Analyzed 76 participants 85 participants 77 participants 70 participants
-8.13  (2.02) -13.97  (1.93) -11.09  (2.01) -6.62  (2.03)
Week6 Number Analyzed 73 participants 81 participants 68 participants 70 participants
-8.26  (2.10) -14.95  (2.00) -11.49  (2.10) -7.63  (2.11)
2.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score.
Hide Description PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Hide Outcome Measure Data
Hide 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 Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 112 113 109 113
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week1 Number Analyzed 110 participants 112 participants 109 participants 113 participants
-0.96  (0.36) -1.31  (0.36) -0.70  (0.36) -1.09  (0.35)
Week2 Number Analyzed 94 participants 104 participants 97 participants 98 participants
-1.72  (0.45) -2.31  (0.44) -1.61  (0.45) -2.25  (0.44)
Week3 Number Analyzed 86 participants 97 participants 88 participants 85 participants
-2.07  (0.52) -3.21  (0.51) -2.71  (0.52) -2.57  (0.52)
Week4 Number Analyzed 80 participants 92 participants 82 participants 77 participants
-2.39  (0.57) -3.69  (0.54) -3.09  (0.56) -2.90  (0.56)
Week5 Number Analyzed 76 participants 85 participants 77 participants 70 participants
-2.19  (0.62) -4.05  (0.60) -2.89  (0.62) -3.26  (0.63)
Week6 Number Analyzed 73 participants 81 participants 68 participants 70 participants
-2.22  (0.64) -4.32  (0.61) -3.15  (0.64) -3.69  (0.64)
3.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score.
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. 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. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Hide Outcome Measure Data
Hide Analysis Population Description
EEfficacy 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 Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 112 113 109 113
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week1 Number Analyzed 110 participants 112 participants 109 participants 113 participants
-0.54  (0.27) -0.83  (0.27) -0.71  (0.27) -0.59  (0.27)
Week2 Number Analyzed 94 participants 104 participants 97 participants 98 participants
-1.08  (0.37) -1.46  (0.36) -1.76  (0.36) -0.72  (0.36)
Week3 Number Analyzed 86 participants 97 participants 88 participants 85 participants
-1.64  (0.41) -2.41  (0.39) -2.27  (0.40) -1.14  (0.40)
Week4 Number Analyzed 80 participants 92 participants 82 participants 77 participants
-2.36  (0.46) -2.90  (0.44) -2.94  (0.46) -0.81  (0.46)
Week5 Number Analyzed 76 participants 85 participants 77 participants 70 participants
-2.31  (0.52) -3.24  (0.50) -3.19  (0.52) -0.85  (0.52)
Week6 Number Analyzed 73 participants 81 participants 68 participants 70 participants
-2.34  (0.55) -3.48  (0.52) -3.24  (0.55) -1.20  (0.55)
4.Secondary Outcome
Title Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S)
Hide 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 Baseline, Weeks 1, 2, 3, 4, 5, and 6
Hide Outcome Measure Data
Hide 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 Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 112 113 109 113
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week1 Number Analyzed 111 participants 112 participants 109 participants 113 participants
-0.13  (0.06) -0.18  (0.06) -0.09  (0.06) -0.15  (0.06)
Week2 Number Analyzed 95 participants 104 participants 97 participants 98 participants
-0.26  (0.08) -0.36  (0.08) -0.34  (0.08) -0.25  (0.08)
Week3 Number Analyzed 86 participants 97 participants 88 participants 85 participants
-0.38  (0.09) -0.52  (0.09) -0.50  (0.09) -0.36  (0.09)
Week4 Number Analyzed 81 participants 92 participants 82 participants 77 participants
-0.48  (0.09) -0.62  (0.09) -0.50  (0.09) -0.40  (0.09)
Week5 Number Analyzed 76 participants 85 participants 77 participants 70 participants
-0.45  (0.11) -0.81  (0.10) -0.56  (0.10) -0.52  (0.11)
Week6 Number Analyzed 73 participants 81 participants 68 participants 70 participants
-0.52  (0.11) -0.85  (0.11) -0.62  (0.11) -0.57  (0.11)
5.Secondary Outcome
Title Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6.
Hide 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 double-blind 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 Baseline, Weeks 1, 2, 3, 4, 5, and 6
Hide Outcome Measure Data
Hide 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 Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 112 113 109 113
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week1 Number Analyzed 111 participants 112 participants 109 participants 113 participants
3.87  (0.92) 3.84  (0.96) 4.01  (0.93) 3.92  (1.04)
Week2 Number Analyzed 112 participants 113 participants 109 participants 113 participants
3.87  (1.10) 3.68  (1.02) 3.79  (1.13) 3.88  (1.26)
Week3 Number Analyzed 112 participants 113 participants 109 participants 113 participants
3.89  (1.20) 3.53  (1.04) 3.77  (1.20) 3.92  (1.36)
Week4 Number Analyzed 112 participants 113 participants 109 participants 113 participants
3.83  (1.23) 3.51  (1.16) 3.81  (1.23) 3.90  (1.36)
Week5 Number Analyzed 112 participants 113 participants 109 participants 113 participants
3.92  (1.27) 3.42  (1.23) 3.76  (1.30) 3.86  (1.48)
Week6 Number Analyzed 112 participants 113 participants 109 participants 113 participants
3.90  (1.32) 3.49  (1.30) 3.78  (1.33) 3.83  (1.49)
Time Frame Adverse events were monitored from signing of the informed consent form until follow-up for up to 30 days after the last dose of study medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Hide Arm/Group Description Brexpiprazole 1 mg tablet once daily for 6 weeks. Brexpiprazole 2 mg tablet once daily for 6 weeks. Brexpiprazole 4 mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks.
All-Cause Mortality
Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/115 (0.00%)   0/114 (0.00%)   0/113 (0.00%)   0/116 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/115 (6.96%)   5/114 (4.39%)   5/113 (4.42%)   5/116 (4.31%) 
Blood and lymphatic system disorders         
Eosinophilia  1/115 (0.87%)  0/114 (0.00%)  0/113 (0.00%)  0/116 (0.00%) 
Gastrointestinal disorders         
Gastric ulcer haemorrhage  0/115 (0.00%)  1/114 (0.88%)  0/113 (0.00%)  0/116 (0.00%) 
Investigations         
Blood creatine phosphokinase increased  1/115 (0.87%)  0/114 (0.00%)  0/113 (0.00%)  0/116 (0.00%) 
Electroencephalogram abnormal  1/115 (0.87%)  0/114 (0.00%)  0/113 (0.00%)  0/116 (0.00%) 
Psychiatric disorders         
Schizophrenia  7/115 (6.09%)  5/114 (4.39%)  4/113 (3.54%)  5/116 (4.31%) 
Psychiatric symptom  1/115 (0.87%)  0/114 (0.00%)  0/113 (0.00%)  0/116 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asphyxia  0/115 (0.00%)  0/114 (0.00%)  1/113 (0.88%)  0/116 (0.00%) 
1
Term from vocabulary, MedDRA Ver. 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brexpiprazole 1mg Brexpiprazole 2mg Brexpiprazole 4mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/115 (42.61%)   46/114 (40.35%)   49/113 (43.36%)   56/116 (48.28%) 
Gastrointestinal disorders         
Constipation  8/115 (6.96%)  8/114 (7.02%)  7/113 (6.19%)  9/116 (7.76%) 
Vomiting  7/115 (6.09%)  5/114 (4.39%)  8/113 (7.08%)  4/116 (3.45%) 
Diarrhoea  4/115 (3.48%)  3/114 (2.63%)  6/113 (5.31%)  2/116 (1.72%) 
Nausea  4/115 (3.48%)  6/114 (5.26%)  3/113 (2.65%)  2/116 (1.72%) 
Dental caries  6/115 (5.22%)  0/114 (0.00%)  4/113 (3.54%)  1/116 (0.86%) 
Infections and infestations         
Nasopharyngitis  12/115 (10.43%)  8/114 (7.02%)  10/113 (8.85%)  11/116 (9.48%) 
Investigations         
Blood prolactin increased  1/115 (0.87%)  3/114 (2.63%)  7/113 (6.19%)  3/116 (2.59%) 
Nervous system disorders         
Headache  8/115 (6.96%)  9/114 (7.89%)  3/113 (2.65%)  5/116 (4.31%) 
Akathisia  2/115 (1.74%)  4/114 (3.51%)  6/113 (5.31%)  8/116 (6.90%) 
Psychiatric disorders         
Schizophrenia  20/115 (17.39%)  13/114 (11.40%)  23/113 (20.35%)  28/116 (24.14%) 
1
Term from vocabulary, MedDRA Ver. 16.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Trials
Organization: Otsuka Pharmaceutical Co., Ltd.
EMail: CL_OPCJ_RDA_Team@otsuka.jp
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT01451164     History of Changes
Other Study ID Numbers: 331-10-002
JapicCTI-111631 ( Other Identifier: JAPIC )
First Submitted: October 11, 2011
First Posted: October 13, 2011
Results First Submitted: September 11, 2019
Results First Posted: October 3, 2019
Last Update Posted: October 3, 2019