Safety and Efficacy of Brexpiprazole in the Treatment of Schizophrenia

Last updated: April 15, 2025
Sponsor: Otsuka Beijing Research Institute
Overall Status: Completed

Phase

3

Condition

Mood Disorders

Tourette's Syndrome

Psychosis

Treatment

Brexpiprazole

Aripiprazole

Clinical Study ID

NCT03874494
331-403-00027
  • Ages 18-65
  • All Genders

Study Summary

This study is a phase III, multicenter, randomized, double-blind, active-controlled, non-inferiority trial designed to assess the efficacy and safety of Brexpiprazole in the Treatment of Adults With Acute Schizophrenia. A total of approximately 370 subjects will be included in the study, and randomized to Brexpiprazole (24 mg/d) or Aripiprazole (1020 mg/d) in a 1:1 ratio.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Provide written informed consent form by subjects and subject's legal guardian orlegally acceptable representative.

  2. The subjects and subject's legal guardian or legally acceptable representative havethe ability to understand the nature of the trial, agree to comply with theprescribed medication and dosage regimens, complete the scheduled visits, report theadverse events and concomitant medication to investigators, and to be reliably ratedon psychiatrically scales.

  3. At the time of signing informed consent, 18 ≤ age of the subject ≤ 65.

  4. Subjects who are diagnosed with schizophrenia according to Diagnostic andStatistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)and confirmed by Mini International Neuropsychiatric Interview (MINI).

  5. Subjects who are experiencing an acute exacerbation of psychotic symptoms and markeddeterioration of usual function as demonstrated by meeting ALL of the followingcriteria at the screening and baseline visit:

● PANSS total score ≥ 70;

  • Score ≥ 4 on at least 2 of the following PANSS items :

( P2 Conceptual disorganization, P3 Hallucinatory behavior, P6 Suspiciousness /persecution, G9 Unusual thought content ) ● CGI-S score ≥ 4;

  1. Subjects willing to discontinue all prohibited psychotropic medications to meetprotocol-required washouts prior to and during the trial period.

Exclusion

Exclusion Criteria:

  1. From ICF to 30 days after the last dose, females of childbearing potential and malesubjects who are not willing or cannot practice contraceptive methods.

  2. Females who are pregnant or breastfeeding.

  3. Subjects who have been hospitalized for > 21 days for the current acute episode atthe time of the Baseline visit, excluding hospitalization for psychosocial reasons.

  4. Subjects with improvement of ≥ 30% in total PANSS score between the screening andbaseline assessment. Improvement in PANSS score= (score at screening-score atbaseline)/ (score at screening-30)*100%.

  5. Subjects with schizophrenia who are considered resistant/refractory to antipsychotictreatment by history of failure to respond to 2 adequate different antipsychoticmedications with a minimum of 6 weeks at clinically efficacious tolerated doses.Subjects who have a systemic treatment of clozapine.

  6. Subjects with a current DSM-IV-TR Axis I diagnosis (including but not limited to):schizoaffective disorder, MDD, bipolar disorder, post-traumatic stress disorder,anxiety disorders, delirium, dementia, amnestic or other cognitive disorders.

  7. Subjects with a current DSM-IV-TR Axis II diagnosis: borderline, paranoid,histrionic, schizotypal, schizoid, or antisocial personality disorders.

  8. Subjects who present a serious risk of suicide:

● Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 or 5 and meetingthe criteria for this C-SSRS Item 4 or 5 occurred within the last 6 months; OR

● Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items andmeeting the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurredwithin the last 2 years; OR

● Subjects who, in the opinion of the investigator, present a serious risk ofsuicide

  1. Subjects with clinically diagnosed tardive dyskinesia, as determined by a score of ≥ 3 in Item 8 of the AIMS at the Screening visit.

  2. Subjects with a score of 5 in the BARS global clinical assessment of akathisia atScreening or Baseline.

  3. Subjects who have met DSM-IV-TR criteria for substance abuse or dependence withinthe 180 days prior to Screening Visit; including alcohol and benzodiazepines, butexcluding caffeine and nicotine.

  4. Subjects with uncontrolled thyroid disease and/or abnormal free thyroxine (FT4)examination results at Screening, unless it has been confirmed by the investigatorthat the condition has been stabilized by medication > 90 days before screening

  5. Subjects with type I diabetes or uncontrolled type II diabetes. Subjects with typeII diabetes may be eligible for the trial if their condition is stable as determinedby satisfying ALL of the following criteria:

  • HbA1c < 7.0%, AND

  • Glucose must be ≤ 125 mg/dL or ≤ 6.94 mmol/L (fasting) or < 200 mg/dL or < 11.1mmol/L (non-fasting) at Screening. If the non-fasting glucose is ≥ 200 mg/dL or ≥ 11.1 mmol/L, subjects must be retested in a fasted state and the retest valuemust be ≤ 125 mg/dL or ≤ 6.94 mmol/L, AND

  • Subjects have maintained a stable regimen of oral anti-diabetic medication(s)for at least 28 days prior to screening or diabetes has been well-controlled bydiet for at least 28 days prior to screening, AND

  • Subjects have not had any hospitalizations within the 12 months prior toscreening due to diabetes or complications related to diabetes, AND

  • Subjects whose diabetes is not newly diagnosed during screening for the trial.

  1. Subjects with uncontrolled hypertension (diastolic blood pressure > 95 mmHg in anyposition) or symptomatic hypotension, or orthostatic hypotension which is defined asa decrease of ≥ 30 mmHg in systolic blood pressure and/or a decrease of ≥ 20 mmHg indiastolic blood pressure after at least 3 minutes standing compared to the previoussupine blood pressure, OR development of symptoms.

  2. Subjects with a history of ischemic heart disease or history of myocardialinfarction, congestive heart failure (whether controlled or uncontrolled),angioplasty, stenting, or coronary artery bypass surgery.

  3. Subjects who have a history or severe organic disease of vital organs (including butnot limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic,hematologic, or immunologic disease).

  4. Subjects with epilepsy or a history of seizures, except for a single seizureepisode, for instance childhood febrile seizure and post traumatic or alcoholwithdrawal.

  5. The following laboratory test and ECG results are exclusionary:

  1. Platelets ≤ 75,000/mm3 (≤ 75 x 109 /L) 2) Hemoglobin ≤ 9 g/dL (90 g/L) 3)Neutrophils ≤ 1,000/mm3 (1 x 109 /L) 4) AST or ALT > 2 × ULN 5) CPK > 3 × ULN 6)Creatinine ≥ 2 mg/dL (176.8 µmol/L) 7) HbA1c ≥ 7.0% 8) QTc ≥ 450 msec (for males) or ≥ 470 msec (for females) in ECG 19. Subjects who received ECT within 60 days ofscreening. 20. Subjects with a history of neuroleptic malignant syndrome (NMS). 21.Subjects with a history of true allergic response (ie, not intolerance) to more thanone class of medications.
  1. Subjects who participated in a clinical trial within the last 90 days or whoparticipated in two or more clinical trials within the past year.

  2. Any subject who, in the opinion of the investigator, should not participate in thetrial.

Study Design

Total Participants: 371
Treatment Group(s): 2
Primary Treatment: Brexpiprazole
Phase: 3
Study Start date:
November 27, 2019
Estimated Completion Date:
September 06, 2021

Study Description

Screening Phase: It will begin when informed consent form (ICF) is signed and be a maximum of 14 days, to evaluate the inclusion/exclusion criteria, collect information such as demographic data, medical history, wash out previous antipsychotic agents and other prohibited concomitant medications.

Double-blind Treatment Phase: It lasts 6 weeks; the purpose is to compare the efficacy and safety of Brexpiprazole with Aripiprazole in the treatment of adults with acute schizophrenia.

Follow-up Phase: All subjects will be followed up for safety reasons via telephone contact or clinic visit 30 (+ 2) days after the last dose of investigational medicinal product, collecting safety information (adverse events and concomitant medication).

Connect with a study center

  • No.15 Yanyin Road, Yanta District

    Xi'an, Shanxi 710061
    China

    Site Not Available

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