MAintain the Efficacy and Safety in Treatment of Schizophrenia After Switching to Long-acTing Injectable aRipiprazole From Oral Atypical Antipsychotics (MAESTRO)

Interventional, multicenter, open-label, 20 weeks study

• To identify efficacy and safety in switching from oral aripiprazole to Abilify Maintena.
• To identify efficacy and safety in switching from oral atypical antipsychotics other than aripiprazole to Abilify Maintena

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Antipsychotics; Long-Acting Injection; LAI; Aripiprazole
• Intervention / Treatment: Drug: Abilify maintena

Detailed Description

We would like to evaluate the efficacy and safety when switching to Abilify Maintena according to the approved indication of Abilify Maintena, for subjects who are taking oral antipsychotic drugs. It is expected that this will serve as a basis for suggesting a successful switching guideline from oral antipsychotics to Abilify Maintena, which can be applicable in clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Medical Center
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
  • Daegu, Korea, Republic of
    • Yeungnam University Medical Center
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Daejeon, Korea, Republic of, 35233
    • Eulji University Hospital
  • Daejeon, Korea, Republic of, 35365
    • Konyang University Hospital
  • Gwangju, Korea, Republic of
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Incheon, Korea, Republic of
    • International St. Mary's hospital
  • Pusan, Korea, Republic of
    • Pusan National University Yangsan Hospital
  • Pusan, Korea, Republic of
    • Inje University Haeundae Paik Hospital
  • Seoul, Korea, Republic of
    • Ewha Womans University Mokdong Hospital
  • Seoul, Korea, Republic of
    • Eulji General Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hosipital
  • Chungcheongbuk-do
    • Chungju, Chungcheongbuk-do, Korea, Republic of, 27376
      • Konkuk University Chungju hospital
  • Chungcheongnam-do
    • Gongju, Chungcheongnam-do, Korea, Republic of, 32601
      • Gongju National Hospital
  • Gyeonggi-do
    • Guri-si, Gyeonggi-do, Korea, Republic of
      • Hanyang University GURI Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • CHA Bundang Medical Center
    • Seongnam-si,, Gyeonggi-do, Korea, Republic of
      • Seoul National University Bundang Hospital
    • Uijeongbu Si, Gyeonggi-do, Korea, Republic of
      • The Catholic University of Korea Uijeongbu St. Mary's Hospital
    • Yongin-si, Gyeonggi-do, Korea, Republic of, 17089
      • Yong-in Mental Hospital
  • Jeju-do
    • Jeju, Jeju-do, Korea, Republic of, 63241
      • Jeju National University Hospital
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, Korea, Republic of
      • Chonbuk National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Subjects who voluntarily consented to participating in the clinical trial.
2. Male and female legally aged ≥19 and < 65 years.
3. Subjects who were diagnosed of schizophrenia as defined by DSM diagnostic criteria, and were diagnosed of schizophrenia for at least for 2 years prior to screening.

4. Subjects with all of the following schizophrenia clinical features:

   A. Outpatient subjects, with no hospitalization for worsening of schizophrenia within 3 months prior to screening.

   B. Subjects who have no more than a moderate rating on the PANSS total score≤80 C. 4 individual PANSS items, which are concerning to psychotic symptom (P2. conceptual disorganization, P3. hallucinatory behavior, P6. suspiciousness/persecution, G9. unusual thought content), score≤4.

   D. CGI-S score ≤4 (moderately ill).

5. Subjects who take atypical antipsychotic drugs with the therapeutic effective dose (as specified in each label) for schizophrenia treatment, and should be maintained on the type and dose of the current antipsychotic drugs (including both typical and atypical antipsychotic drugs) for at least 4 weeks prior to the screening.
6. Subjects who need antipsychotic treatment (other than clozapine), and would be stable when switching to Abilify Maintena on the investigator's judgement.
7. Subjects must exhibit willingness, physiologic capability, and an educational level sufficient to comply with all protocol procedures as per the investigator's judgment.

Exclusion criteria

1. Subject who showed medically significant adverse events or intolerance with aripiprazole during screening period or as prior experiences.
2. Subjects with a current DSM diagnostic criteria-based diagnosis other than schizophrenia, including Schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, neurocognitive disorder due to Alzheimer's or similar diseases, amnesia, borderline, paranoid, histrionic, schizotypal, schizoid, antisocial or other cognitive or personality disorders.
3. Subjects with diseases of the central nervous system that may impact the assessment of the psychotic symptoms as per investigator's opinion.
4. Subjects who have been treated with clozapine, electroconvulsive therapy (ECT) or other long-acting injectable antipsychotic drugs within 3 months prior to the screening.

5. Subjects who have been treated more than 2 oral antipsychotic drugs (including both typical and atypical antipsychotic drugs) with the minimum therapeutic effective dose (as specified in each label) for schizophrenia treatment at screening.

   (e.g. Aripiprazole≥10 mg/day, Olanzapine≥10 mg/day, Risperidone≥2 mg/day, Quetiapine ≥150 mg/day)

6. Subjects who have been treated with oral antipsychotic drugs (including both typical and atypical antipsychotic drugs) exceeding maximum maintenance dose (as specified in each label) at screening.

   (e.g. Aripiprazole>30 mg/day, Olanzapine>20 mg/day, Risperidone > 6 mg/day, Quetiapine > 750 mg/day)

7. Subjects with a significant risk of violent behavior or a significant risk of committing suicide based on history or investigator's judgment.
8. Subjects had a history of seizures, neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or other medical condition that would expose them to undue risk or interfere with study assessments.
9. Significant history of drug abuse disorder (excluding caffeine and nicotine, including alcohol, as defined in DSM-5 substance use disorder or in the opinion of the investigator) within the last 6 months prior to screening.
10. Subjects who participated in another interventional clinical trial within 30 days prior to screening.
11. Pregnant or lactating women, or women of childbearing potential who are not willing to or not able to use contraceptive methods (sexual abstinence; oral, implanted or injection hormone contraceptive methods; intrauterine device or condom; barrier contraceptive methods such as diaphragm and spermicide), accepted to avoid pregnancy until the end of the clinical trial.
12. Subjects having any other clinically significant finding of the physical examination or laboratory value that make investigator consider that it would be inappropriate to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Schizophrenia patients who are taking oral aripiprazole will be switched to Abilify maintena	Drug: Abilify maintena; Switching from oral atypical antipsychotics to long-acting injectable aripiprazole (Abilify maintena); Other Names: long-acting injectable aripiprazole
Experimental: Group 2; Schizophrenia patients who are taking other oral atypical antipsychotics will be switched to Abilify maintena	Drug: Abilify maintena; Switching from oral atypical antipsychotics to long-acting injectable aripiprazole (Abilify maintena); Other Names: long-acting injectable aripiprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANSS total score	Change in PANSS total score from baseline to Week 16	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGI-S	Change in CGI-S (severity) from baseline to Week 16	16 weeks
CGI-I	Mean CGI-I (improvement) score at Week 16	16 weeks
PANSS positive and negative subscale score	Change in PANSS positive and negative subscale score from baseline to Week 16	16 weeks
IAQ score	Mean IAQ score at Week 16	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
study discontinuation rates	Comparison the study discontinuation rates between Group 1 and Group 2	16 weeks
study discontinuation rates	Comparison the study discontinuation rates in Group 2 depending on the other oral atypical antipsychotics	16 weeks
proportion of subjects who have more than 20% increased rating on the PANSS total score	Comparison the proportion of subjects who have more than 20% increased rating on the PANSS total score from baseline to Week 16 between Group 1and Group 2	16 weeks
proportion of subjects who have more than 20% increased rating on the PANSS total score	Comparison the proportion of subjects who have more than 20% increased rating on the PANSS total score from baseline to Week 16 in Group 2 depending on the other oral atypical antipsychotics	16 weeks

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jun Soo Kwon, Dr., Seoul National University Hospital

Publications and helpful links

General Publications

• Aripiprazole Investigator Brochure, Version No. 20, 16 Aug 2016
• Regier DA, Narrow WE, Rae DS, Manderscheid RW, Locke BZ, Goodwin FK. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993 Feb;50(2):85-94. doi: 10.1001/archpsyc.1993.01820140007001.
• Hong Kyu Ihm et al. Factors Related to Medication Adherence in Outpatients with Schizophrenia under More Than 5 Years of Treatment. J Korean Neuropsychiatr Assoc 2016; 55(4):397-406
• Hyun-Ku Kang, et al. Safety and Effectiveness of Long Acting Injectable Antipsychotic Paliperidone Palmitate Treatment in Schizophrenics: A 24-Week Open-Label Study. Korean J Biol Psychiatry 2013;20:111-117
• Gilbert PL, Harris MJ, McAdams LA, Jeste DV. Neuroleptic withdrawal in schizophrenic patients. A review of the literature. Arch Gen Psychiatry. 1995 Mar;52(3):173-88. doi: 10.1001/archpsyc.1995.03950150005001. No abstract available.
• Gitlin M, Nuechterlein K, Subotnik KL, Ventura J, Mintz J, Fogelson DL, Bartzokis G, Aravagiri M. Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. Am J Psychiatry. 2001 Nov;158(11):1835-42. doi: 10.1176/appi.ajp.158.11.1835.
• Kane JM, Sanchez R, Perry PP, Jin N, Johnson BR, Forbes RA, McQuade RD, Carson WH, Fleischhacker WW. Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012 May;73(5):617-24. doi: 10.4088/JCP.11m07530.
• Naber D, Hansen K, Forray C, Baker RA, Sapin C, Beillat M, Peters-Strickland T, Nylander AG, Hertel P, Andersen HS, Eramo A, Loze JY, Potkin SG. Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia. Schizophr Res. 2015 Oct;168(1-2):498-504. doi: 10.1016/j.schres.2015.07.007. Epub 2015 Jul 29.
• Seockhoon Chung, Chang Yoon Kim. et al. Effectiveness and Tolerability of Long-Acting Risperidone：A 12 Weeks, Multi-center Switching Study from Oral Antipsychotics. Korean J Psychopharmacol 16/2:109-120, 2005
• Fleischhacker WW, Sanchez R, Perry PP, Jin N, Peters-Strickland T, Johnson BR, Baker RA, Eramo A, McQuade RD, Carson WH, Walling D, Kane JM. Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study. Br J Psychiatry. 2014 Aug;205(2):135-44. doi: 10.1192/bjp.bp.113.134213. Epub 2014 Jun 12.

Helpful Links

• Clinical trial guideline for Antipsychotics; Ministry Food And Drug, 2015.09.
• The survey of Mental Disorders in Korea; Ministry of Health and Welfare, 2016
• Abilify Maintena Package Insert in Korea
• Abilify Package Insert in Korea

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): November 19, 2021
• Study Completion (Actual): November 19, 2021

Study Registration Dates

• First Submitted: December 13, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 18, 2017

Study Record Updates

• Last Update Posted (Actual): December 17, 2021
• Last Update Submitted That Met QC Criteria: December 16, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: aripiprazole; Long-Acting Injection
• 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; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 031-402-00129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No