Clinical trial NCT03376763: MAintain the Efficacy and Safety in Treatment of Schizophrenia After Switching to Long-acTing Injectable aRipiprazole From Oral Atypical Antipsychotics
Official title: MAintain the Efficacy and Safety in Treatment of Schizophrenia After Switching to Long-acTing Injectable aRipiprazole From Oral Atypical Antipsychotics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Antipsychotics
Long-Acting Injection
LAI
Aripiprazole
Keywords: aripiprazole
Long-Acting Injection
Lead sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-12-18
Enrollment: 201
Sex: ALL
Minimum age (years): 19
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: PANSS total score
timeFrame: 16 weeks
Secondary outcomes:
measure: CGI-S
timeFrame: 16 weeks
measure: CGI-I
timeFrame: 16 weeks
measure: PANSS positive and negative subscale score
timeFrame: 16 weeks
measure: IAQ score
timeFrame: 16 weeks
Other outcomes:
measure: study discontinuation rates
timeFrame: 16 weeks
measure: study discontinuation rates
timeFrame: 16 weeks
measure: proportion of subjects who have more than 20% increased rating on the PANSS total score
timeFrame: 16 weeks
measure: proportion of subjects who have more than 20% increased rating on the PANSS total score
timeFrame: 16 weeks
Locations:
city: Chungju
country: Korea, Republic of
facility: Konkuk University Chungju Hospital
state: Chungcheongbuk-do
city: Gongju
country: Korea, Republic of
facility: Gongju National Hospital
state: Chungcheongnam-do
city: Guri-si
country: Korea, Republic of
facility: Hanyang University Guri Hospital
state: Gyeonggi-do
city: Seongnam-si,
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Cha Bundang Medical Center
state: Gyeonggi-do
city: Uijeongbu Si
country: Korea, Republic of
facility: The Catholic University of Korea Uijeongbu ST. Mary'S Hospital
state: Gyeonggi-do
city: Yongin-si
country: Korea, Republic of
facility: Yong-In Mental Hospital
state: Gyeonggi-do
city: Jeju
country: Korea, Republic of
facility: Jeju National University Hospital
state: Jeju-do
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
state: Jeollabuk-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Eulji University Hospital
city: Daejeon
country: Korea, Republic of
facility: Konyang University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Incheon
country: Korea, Republic of
facility: International St. Mary's Hospital
city: Pusan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Eulji General Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hosipital
Study officials:
affiliation: Seoul National University Hospital
name: Jun Soo Kwon, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aripiprazole Investigator Brochure, Version No. 20, 16 Aug 2016
citation: 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.
citation: 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
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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
citation: 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.