Efficacy Study of OPC-34712 in Adults With Acute Schizophrenia (BEACON)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01393613
First received: July 11, 2011
Last updated: October 26, 2015
Last verified: October 2015
  Purpose
The purpose of this study is to assess the efficacy, safety, and tolerability of fixed doses of OPC-34712 versus placebo for the treatment of adult subjects with an acute relapse of schizophrenia.

Condition Intervention Phase
Acute Schizophrenia
Drug: OPC-34712
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Fixed-dose OPC-34712 in the Treatment of Adults With Acute Schizophrenia

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    Severity of illness for each participant was rated using the CGI-S, which was the key 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 Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. [ Time Frame: Baseline, Week 3 and Week 6 ] [ Designated as safety issue: No ]
    PSP is a validated clinician-rated scale that measures personal and social functioning in 4 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 to determine 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.

  • Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    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/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). The analysis of secondary endpoints was conducted if both comparisons of brexpiprazole 4 mg/day vs placebo and brexpiprazole 2 mg/day vs placebo of the primary endpoint were significant. Although only the comparison of brexpiprazole 4 mg/day vs placebo met the gatekeeping threshold in the primary analysis, statistical testing for the other doses was reported for information.

  • Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    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 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 Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Response at Week 6. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    The response rate was defined as reduction of ≥30% from Baseline in PANSS Total Score or CGI-I score of 1 or 2.

  • Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    Participants discontinued for lack of efficacy during the trial were reported here.

  • Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe).

  • Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).

  • Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).

  • Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).

  • Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

  • Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6 ] [ Designated as safety issue: No ]
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).


Enrollment: 674
Study Start Date: July 2011
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose 3 OPC 34712
Higher dose, tablet, once daily, for six weeks
Drug: OPC-34712
Higher dose tablet, once daily, for six weeks,
Experimental: Dose 2 OPC 34712
Middle dose, tablet, once daily, for six weeks
Drug: OPC-34712
Middle dose tablet, once daily, for six weeks
Experimental: Dose 1 OPC 34712
Lower dose, tablet, once daily, for six weeks
Drug: OPC-34712
Lower dose tablet, once daily, for six weeks
Placebo Comparator: Placebo
Placebo, once daily, for six weeks
Drug: Placebo
Placebo, once daily, for six weeks

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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects between 18 and 65 years of age, with a diagnosis of schizophrenia, as defined by DSM-IV-TR criteria
  2. Subjects who have been recently hospitalized or who would benefit from hospitalization for an acute relapse of schizophrenia
  3. Subjects experiencing an acute exacerbation of psychotic symptoms
  4. Other protocol specific inclusion criteria may apply

Exclusion Criteria:

  1. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug
  2. Subjects with a current DSM-IV-TR Axis I diagnosis of:

    • Schizoaffective disorder
    • MDD
    • Bipolar disorder
    • Delirium, dementia, amnestic or other cognitive disorder
    • Borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder
  3. Subjects presenting with a first episode of schizophrenia
  4. Other protocol specific exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01393613

  Show 60 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Aleksandar Skuban, M.D. Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01393613     History of Changes
Other Study ID Numbers: 331-10-230 
Study First Received: July 11, 2011
Results First Received: August 11, 2015
Last Updated: October 26, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
India: Drugs Controller General of India

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 23, 2016