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

NCT01668797 | Completed Phase 3 Results DMC

• 2 other identifiers: 331-10-2322011-005766-38
• Study Type: interventional
• Target: 524
• Locations: 8 countries
• Sites: 49

Brief Summary

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

Conditions

Acute Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.

  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.

  From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks

Secondary Outcomes (1)

• Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase

  Baseline and Week 52/Early Termination

Other Outcomes (27)

• Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase

  Weeks 6, 12, 24, 36 and 52

• Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis

  Baseline and Weeks 6, 12, 24, 36 and 52

• Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis

  Baseline and Weeks 6, 12, 24, 36 and 52

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo comparator for 52 weeks

Drug: Placebo

Brexpiprazole (OPC-34712)

EXPERIMENTAL

Brexpiprazole (OPC-34712) for 52 weeks

Drug: Brexpiprazole

Interventions

Brexpiprazole DRUG

Brexpiprazole tablets 1 to 4 mg /day

Brexpiprazole (OPC-34712)

Placebo DRUG

Placebo comparator for 52 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Quintiles, Inc.: collaborator

Study Sites (49)

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Anaheim, California, 92805, United States

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Cerritos, California, 90703, United States

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Garden Grove, California, 92845, United States

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San Diego, California, 92102, United States

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San Diego, California, 92103, United States

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Tampa, Florida, 33613, United States

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Hoffman Estates, Illinois, 60169, United States

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Saint Charles, Missouri, 63304, United States

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St Louis, Missouri, 63141, United States

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North Platte, Nebraska, 69101, United States

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Las Vegas, Nevada, 89102, United States

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Memphis, Tennessee, 38119, United States

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Dallas, Texas, 75231, United States

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Richmond, Virginia, 23230, United States

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Barranquilla, 00000, Colombia

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Bello, 00000, Colombia

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Bogotá, 00000, Colombia

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Pereira, 00000, Colombia

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Kota Bharu, Kelantan, 15586, Malaysia

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Kuala Lumpur, Kuala Lumpur, 56000, Malaysia

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Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

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Kajang, Selangor, 43000, Malaysia

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Sabak Bernam, 88815, Malaysia

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San Juan, 00918, Puerto Rico

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San Juan, 00927, Puerto Rico

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Arad, 310022, Romania

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Brasov, 500123, Romania

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Bucharest, 041914, Romania

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Craiova, 200473, Romania

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Focşani, 620165, Romania

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Iași, 700282, Romania

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Piteşti, 110069, Romania

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Târgovişte, 130086, Romania

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Belgrade, 11000, Serbia

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Belgrade, 11040, Serbia

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Kragujevac, 34000, Serbia

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Novi Kneževac, 23330, Serbia

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Novi Sad, 21000, Serbia

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Denizli, 20070, Turkey (Türkiye)

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Diyarbakır, 21280, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

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Kharkiv, 61036, Ukraine

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Kharkiv, 61068, Ukraine

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Kherson,Vil. Stepanivka, 73488, Ukraine

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Kyiv, 02660, Ukraine

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Kyiv, 04080, Ukraine

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Lviv, 79021, Ukraine

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Odesa, 65014, Ukraine

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Simferopol, 95006, Ukraine

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Related Publications (4)

• 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.

  PMID: 35235720 DERIVED

• 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.

  PMID: 34901863 DERIVED

• 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.

  PMID: 30306884 DERIVED

• 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.

  PMID: 27566723 DERIVED

MeSH Terms

Interventions

brexpiprazole

Limitations and Caveats

As the interim analysis results were positive, the trial was completed as it achieved the primary endpoint of a significant delay in time to impending relapse for participants randomized to brexpiprazole when compared to participants in placebo.

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800 562-3974

Study Officials

• Aleksandar Skuban, M.D.

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2012
• First Posted: August 20, 2012
• Study Start: October 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: February 1, 2015
• Last Updated: January 13, 2017
• Results First Posted: January 13, 2017

Record last verified: 2016-11

Locations

UA (8); TU (3); RO (8); US (14); SE (5); MY (5); CO (4); PR (2)