Clinical trial NCT01668797: Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Schizophrenia
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2012-08-20
Enrollment: 524
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.
timeFrame: From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks
Secondary outcomes:
measure: Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase
timeFrame: Baseline and Week 52/Early Termination
Other outcomes:
measure: Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase
timeFrame: Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis
timeFrame: Baseline, Weeks 6, 12, 24, 36 and 52
measure: Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis
timeFrame: Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis
timeFrame: Baseline and Weeks 24 and 52
measure: Mean Change From Baseline in PSP Scale Score - LOCF Analysis
timeFrame: Baseline and Weeks 24 and 52
measure: Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis
timeFrame: Baseline and Weeks 12, 24, 36 and 52
measure: Mean Change From Baseline in GAF Scale Score - LOCF Analysis
timeFrame: Baseline and Weeks 12, 24, 36 and 52
measure: Percentage of Participants Who Discontinued Due to All Causes
timeFrame: Baseline to Week 52
measure: Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PEC Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
measure: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis
timeFrame: Baseline and Weeks 6, 12, 24, 36 and 52
Locations:
city: Anaheim
country: United States
state: California
city: Cerritos
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: Tampa
country: United States
state: Florida
city: Hoffman Estates
country: United States
state: Illinois
city: St. Charles
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: North Platte
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Memphis
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Barranquilla
country: Colombia
city: Bello
country: Colombia
city: Bogota
country: Colombia
city: Pereira
country: Colombia
city: Kota Bahru
country: Malaysia
state: Kelantan
city: Kajang
country: Malaysia
state: Selangor
city: Kuala Lumpur
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Sabah
country: Malaysia
city: San Juan
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Arad
country: Romania
city: Brasov
country: Romania
city: Bucuresti
country: Romania
city: Craiova
country: Romania
city: Focsani
country: Romania
city: Iasi
country: Romania
city: Pitesti
country: Romania
city: Targoviste
country: Romania
city: Belgrade
country: Serbia
city: Belgrade
country: Serbia
city: Kragujevac
country: Serbia
city: Novi Knezevac
country: Serbia
city: Novi Sad
country: Serbia
city: Denizli
country: Turkey
city: Diyarbakir
country: Turkey
city: Kocaeli
country: Turkey
city: Kharkiv
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kherson,Vil. Stepanivka
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Simferopol
country: Ukraine
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Aleksandar Skuban, M.D.
role: STUDY_DIRECTOR
References:
citation: Correll CU, He Y, Therrien F, MacKenzie E, Meehan SR, Weiss C, Hefting N, Hobart M. Effects of Brexpiprazole on Functioning in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies. J Clin Psychiatry. 2022 Mar 1;83(2):20m13793. doi: 10.4088/JCP.20m13793.
citation: Marder SR, Meehan SR, Weiss C, Chen D, Hobart M, Hefting N. Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies. Schizophr Bull Open. 2021 May 1;2(1):sgab014. doi: 10.1093/schizbullopen/sgab014. eCollection 2021 Jan.
citation: Correll CU, Shi L, Weiss C, Hobart M, Eramo A, Duffy RA, Weiller E, Baker RA. Successful switching of patients with acute schizophrenia from another antipsychotic to brexpiprazole: comparison of clinicians' choice of cross-titration schedules in a post hoc analysis of a randomized, double-blind, maintenance treatment study. CNS Spectr. 2019 Oct;24(5):507-517. doi: 10.1017/S1092852918001086.
citation: Fleischhacker WW, Hobart M, Ouyang J, Forbes A, Pfister S, McQuade RD, Carson WH, Sanchez R, Nyilas M, Weiller E. Efficacy and Safety of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia: a Randomized, Double-Blind, Placebo-Controlled Study. Int J Neuropsychopharmacol. 2017 Jan 1;20(1):11-21. doi: 10.1093/ijnp/pyw076.