Brexpiprazole in Patients With Acute Schizophrenia

Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Active-reference, Flexible-dose Study of Brexpiprazole in Patients With Acute Schizophrenia

To determine the efficacy and safety of brexpiprazole for the treatment of adults experiencing an acute episode of schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Brexpiprazole; Drug: Quetiapine extended release

• Study Type: Interventional
• Enrollment (Actual): 468
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Escondido, California, United States, 92025
      • US009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has schizophrenia, diagnosed according to DSM-IV-TR™ and confirmed by the Mini International Neuropsychiatric Interview (MINI).
• The patient has an acute exacerbation of psychotic symptoms and marked deterioration of usual function.
• The patient is willing to be hospitalised from the Screening Visit through Week 6.
• The patient will benefit from hospitalisation or continued hospitalisation for treatment of a current acute relapse of schizophrenia at study entry.
• The patient has a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding the current episode.
• The patient agrees to protocol-defined use of effective contraception.

Exclusion Criteria:

• The patient has a current Axis I diagnosis (DSM-IV-TR™ criteria) other than schizophrenia established as primary diagnosis.
• The patient suffers from a current Axis II diagnosis (DSM-IV-TR™ criteria).
• The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
• The patient, in the opinion of the investigator or according to Columbia Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide.
• The patient has clinically significant tardive dyskinesia or severe akathisia at enrolment.
• The patient has a history of neuroleptic malignant syndrome.
• The patient has any relevant medical history or current presence of systemic disease.
• The patient has, at the Screening Visit an abnormal ECG or other abnormal ECG tests that are, in the investigator's opinion, clinically significant.
• The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first dose of brexpiprazole.
• The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Once daily as tablets and capsules, orally
Experimental: Brexpiprazole; Patients randomised to brexpiprazole received 1mg/day on Day 1, 2mg/day on Day 2, 3mg/day on Day 3 (uptitration); the dose could be adjusted from Day 4 onwards to 2, 3, or 4mg/day to optimise the clinical effect and tolerability.	Drug: Brexpiprazole; 2-4 mg/day, once daily, tablets, orally
Other: Quetiapine extended release; Active Reference. Patients randomised to quetiapine received 300mg/day on Day 1, 600mg/day on Days 2 and 3 (uptitration); the dose could be adjusted from Day 4 onwards to 400, 600, or 800mg/day to optimise the clinical effect and tolerability.	Drug: Quetiapine extended release; 400-800 mg/day, once daily, encapsulated tablets, orally; Other Names: Seroquel XL®/XR®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in PANSS Total Score	The Positive and Negative Syndrome Scale (PANSS) is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranged from 30 to 210 with a higher score indicating greater severity of symptoms.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in CGI-S Score	The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).	Baseline and Week 6
CGI-I Score at Week 6	The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.	Week 6
Change From Baseline to Week 6 in PANSS Positive Subscale Score	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Positive Subscale score is calculated from 7 items (for example: delusions, conceptual disorganization and hallucinatory behaviour). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Negative Subscale Score	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Negative Subscale score is calculated from 7 items (for example: blunted affect, emotional withdrawal and poor rapport). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS General Psychopathology Subscale score is calculated from 16 items (for example: somatic concern, anxiety and guilt feelings). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Excited Component Score	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Excited Component score is calculated from 5 items (for example: poor impulse control, tension and hostility). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: negative symptoms is calculated from 7 items (for example: blunted affect, emotional withdrawal and motor retardation). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: positive symptoms is calculated from 8 items (for example: delusions, conceptual disorganization and stereotype thinking). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: disorganized thoughts is calculated from 7 items (for example: conceptual disorganization, difficulty in abstract thinking and mannerisms and posturing). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: uncontrolled hostility/excitement is calculated from 4 items (for example: excitement, hostility, and uncooperativeness).Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression	The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: anxiety/depression is calculated from 4 items (for example: anxiety, guilt feelings, and tension). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms	Baseline and Week 6
Discontinuation Due to Lack of Efficacy During the Study	Discontinuation due to lack of efficacy was based on the primary reason for withdrawal	Baseline to Week 6
Response Rate at Week 6	The response rate was defined as a reduction of ≥30% from baseline in PANSS total score OR a CGI-I score of 1 or 2	Baseline and Week 6
Change From Baseline to Week 6 in PSP Total Score	The Personal and Social Performance Scale (PSP) is a clinician-rated scale designed and validated to measure a patient's current level of social functioning. The PSP scale consists of a 100-point single-item rating scale, subdivided into 10 equal intervals. Scores of 1 to 10 indicate lack of autonomy in basic functioning, whereas scores of 91 to 100 reflect excellent functioning. The total score is rated by the investigator and is based on an algorithm which takes both the ratings of the 4 primary domains of PSP, and the combination of these ratings into account. The 4 primary domains are: socially useful activities (including work and study), personal and social relationships, self-care, and disturbing and aggressive behaviours. The 4 domains are assessed on a 6-point scale, from absent to very severe. A higher score indicates a better performance.	Baseline and Week 6
PSP Functional Remission Rate at Week 6	The PSP functional remission rate was defined as a PSP total score ≥71	Week 6
PSP Functional Response Rate at Week 6	The PSP functional response rate was defined as ≥10 point improvement from Baseline on the PSP total score	Week 6
PSP Domain D: Disturbing and Aggressive Behaviours at Week 6	PSP domain D: disturbing and aggressive behaviours were categorised as "aggressive" (corresponding to mild, manifest, marked, severe, or very severe) or "nonaggressive" (corresponding to absent)	Week 6

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Collaborators: Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• EMA EudraCT Results: 2012-002252-17

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 11, 2013
• First Submitted That Met QC Criteria: March 11, 2013
• First Posted (Estimate): March 13, 2013

Study Record Updates

• Last Update Posted (Actual): March 16, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Quetiapine Fumarate; Brexpiprazole
• Other Study ID Numbers: 14644A; 2012-002252-17 (EudraCT Number)