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Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia

Phase 3
Completed
Conditions
Acute Schizophrenia
Interventions
Drug: Placebo
Registration Number
NCT01668797
Lead Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Brief Summary

The purpose of this study is to evaluate the efficacy of brexpiprazole compared with placebo as maintenance treatment in adults with schizophrenia.

Detailed Description

Schizophrenia is a severely debilitating mental illness that affects approximately 1% of the world population. Hallucinations and delusions are the most striking characteristic positive symptoms of schizophrenia; however, more subtle negative symptoms (eg, social withdrawal and lack of emotion, energy, and motivation) may also be present. The first antipsychotics developed for the treatment of schizophrenia were effective against positive symptoms, but showed little efficacy for negative symptoms and were also associated with a high incidence of side effects. Second generation antipsychotics, represent a significant advancement in the treatment of psychotic disorders because they are effective and at the same time exhibit fewer side effects than first generation antipsychotics. Although generally safer than first generation antipsychotics, the second-generation antipsychotics are not devoid of undesirable side effects such as Hyperprolactinemia and weight gain. In addition, the safety of these drugs vary considerably.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
524
Inclusion Criteria
  • Patients age 18 years or older to less than 65 years, inclusive (at time of informed consent)
  • Subjects with a current diagnosis of schizophrenia, as defined by DSM-IV-TR criteria and a history of the illness for at least three years prior to screening (as per subject, family, healthcare provider, or by previous medical records).
  • Subjects with a stable living environment, as demonstrated by the ability to provide contact information for themselves and/or family/friend(s)/caregiver(s).
  • Subjects who showed previous response to antipsychotic treatment in the past year.
  • Subjects who are currently treated with oral or depot antipsychotics other than clozapine or who have had a recent lapse in antipsychotic treatment requiring chronic treatment with antipsychotic medication for stabilization.
  • Subjects who are experiencing a current acute exacerbation of psychotic symptoms requiring stabilization
  • Subjects with a history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment.
Exclusion Criteria
  • Female patients who are breastfeeding or who have a positive pregnancy test (urine) result prior to receiving investigational medicinal product
  • Patients presenting a first episode of schizophrenia based on the clinical judgment of the investigator
  • 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)
  • Subjects experiencing acute depressive symptoms within the past 30 days
  • Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment by history
  • Subjects with a significant risk of violent behavior; who represent a risk of committing suicide
  • Subjects with clinically significant tardive dyskinesia
  • Subjects currently treated with insulin for diabetes.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo comparator for 52 weeks
Brexpiprazole (OPC-34712)BrexpiprazoleBrexpiprazole (OPC-34712) for 52 weeks
Primary Outcome Measures
NameTimeMethod
Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks

The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \>4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content).OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.The measure type, number is Hazard Ratio.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance PhaseBaseline and Week 52/Early Termination

Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \> 4 with an absolute increase of ≥ 2 on that specific item or an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual though content) to a score of \>4 and an absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Current suicidal behavior as assessed by the C-SSRS (ie, an answer of "yes" to any of the questions on the suicidal behavior section of the C-SSRS 5) Violent or aggressive behavior resulting in clinically significant self-injury to another person, or property damage.

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