An Open-Label, Multicenter, Rollover, Long-term Study of Aripiprazole Intramuscular Depot in Participants With Schizophrenia (ASPIRE)

An Open-Label, Multicenter, Rollover, Long-term Study of Aripiprazole Intramuscular Depot in Patients With Schizophrenia

The primary objective of this study was to continue to provide aripiprazole intramuscular (IM) depot treatment (400 milligrams [mg] or 300 mg) to participants with schizophrenia completing the 52-week, open-label safety and tolerability Study 31-08-248. In addition, the secondary objective was to collect additional long-term safety data on aripiprazole IM depot treatment.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Aripiprazole

Detailed Description

This was an open-label study that enrolled participants with schizophrenia who had completed the 52-week, open-label safety and tolerability Study 31-08-248 and continued to provide aripiprazole IM depot treatment.

Participants received this treatment until aripiprazole IM Depot was commercially available in any dosage (including generic formulations) in the country where the study was being conducted or the commercial availability of aripiprazole IM Depot was terminated by the sponsor, or until the study completion date of 06 Dec 2018 was reached.

Eligible participants entered this study at the end of treatment visit (Week 52) of Study 31-08-248. Participants continued to receive aripiprazole IM depot every month (study months were every 4 weeks, which were defined as 28 [-2/+10] days) as a continuation of their previous monthly dose in Study 31-08-248.

• Study Type: Interventional
• Enrollment (Actual): 709
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1405BOA
  • Buenos Aires, Argentina, C1425AHQ
  • Buenos Aires, Argentina, 1900
  • Buenos Aires, Argentina, C1058AAH
  • Mendoza, Argentina, M5500HYF
• Australia
  • Victoria
    • Epping, Victoria, Australia, 3076
    • Frankston, Victoria, Australia, 3199
  • Western Australia
    • Fremantle, Western Australia, Australia, 6959
• Bulgaria
  • Bourgas, Bulgaria, 8000
  • Lovech, Bulgaria, 5500
  • Pazardzhik, Bulgaria, 4400
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria
  • Plovdiv, Bulgaria, 4002
  • Radnevo, Bulgaria, 6260
  • Rousse, Bulgaria, 7003
  • Sofia, Bulgaria, 1431
  • Sofia, Bulgaria, 1113
  • Sofia, Bulgaria, 1632
  • Tserova Koria, Bulgaria
  • Varna, Bulgaria
  • Varna, Bulgaria, 9001
• Chile
  • Santiago, Chile, 7500710
  • Santiago, Chile, 7510186
  • Santiago, Chile, 7580307
  • Santiago, Chile, 8330838
  • Santiago, Chile, 8900085
  • Santiago, Chile, 8780000
  • Temuco, Chile, 4781151
  • Valdivia, Chile, 5090145
• Croatia
  • Zagreb, Croatia, 10000
  • Zagreb, Croatia, 10090
  • Zagreb, Croatia
• Estonia
  • Tallinn, Estonia, 10617
  • Tallinn, Estonia, 10614
  • Tartu, Estonia
  • Tartu, Estonia, 50417
  • Viljandi, Estonia, 71024
• Finland
  • Helsinki, Finland, 250
• Hungary
  • Baja, Hungary, 6500
  • Balassagyarmat, Hungary, 2660
  • Gyõr, Hungary, 9023
• India
  • Bangalore, India
  • Chennai, India
  • Kanpur, India, 208005
  • Pune, India, 411004
  • Tirupati, India, 517507
  • Gujarat
    • Ahmedabad, Gujarat, India, 380006
  • Karnataka
    • Mangalore, Karnataka, India, 575018
• Korea, Republic of
  • Daejeon, Korea, Republic of, 301-721
  • Gwangju, Korea, Republic of, 501-757
  • Incheon, Korea, Republic of, 400-711
  • Seoul, Korea, Republic of, 110-744
• Malaysia
  • Ipoh, Malaysia
  • Kajang, Malaysia
  • Kuala Lumpur, Malaysia, 59100
  • Kuala Lumpur, Malaysia, 56000
• Mexico
  • Mexico, Mexico, 7760
  • San Luis Potosí, Mexico, 78218
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64040
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, 80020
• Philippines
  • Mariveles, Philippines
  • NCR
    • Mandaluyong City, NCR, Philippines, 1553
  • Western Visayas
    • Iloilo City, Western Visayas, Philippines, 5000
• Poland
  • Belchatow, Poland, 97-400
  • Bialystok, Poland, 15-879
  • Bydgoszcz, Poland, 85096
  • Choroszcz, Poland, 16-070
  • Krakow, Poland, 31-501
  • Leszno, Poland, 64-100
  • Sosnowiec, Poland, 41-200
  • Wroclaw, Poland, 50-227
• Puerto Rico
  • San Juan, Puerto Rico, 00918
• Romania
  • Arad, Romania, 310022
  • Bucharest, Romania, 41914
  • Cluj-Napoca, Romania, 400012
  • Craiova, Romania, 200620
  • Oradea, Romania, 410163
  • Pitesti, Romania, 110069
• Russian Federation
  • Leningrad, Russian Federation
  • Lipetsk, Russian Federation, 398007
  • Moscow, Russian Federation, 115522
  • Moscow, Russian Federation, 127083
  • Nizhny Novgorod, Russian Federation, 603152
  • Nizhny Novgorod, Russian Federation, 603155
  • Smolensk, Russian Federation
  • St. Petersburg, Russian Federation, 190121
  • St. Petersburg, Russian Federation, 192019
• Serbia
  • Belgrade, Serbia, 11000
  • Kragujevac, Serbia, 34000
• Slovakia
  • Bardejov, Slovakia
  • Kosice, Slovakia, 041 90
  • Liptovsky Mikulas, Slovakia, 3101
  • Prešov, Slovakia
  • Rimavská Sobota, Slovakia
• South Africa
  • Bellville, South Africa, 7530
  • Pretoria West, South Africa, 1
  • Western Province
    • Cape Town, Western Province, South Africa, 7530
• Spain
  • Barcelona, Spain, 8036
  • Barcelona, Spain, 08006
  • Hospitalet de Llobregat, Spain
• Taiwan
  • Tainan, Taiwan, 704
  • Taipei City, Taiwan, 110
• Thailand
  • Chiang Mai, Thailand
• United States
  • California
    • Bellevue, California, United States, 98007
    • Garden Grove, California, United States, 92845
    • Glendale, California, United States, 91206
    • Glendale, California, United States, 91204
    • Imperial, California, United States, 92251
    • Los Angeles, California, United States, 90024
    • National City, California, United States
    • National City, California, United States, 91950
    • Orange, California, United States, 92868
    • Pasadena, California, United States, 91107
    • Pico Rivera, California, United States, 90660
    • Pico Rivera, California, United States
    • San Bernardino, California, United States, 92408-3304
    • San Diego, California, United States
    • Sherman Oaks, California, United States, 91403
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
  • District of Columbia
    • Washington, District of Columbia, United States
    • Washington, District of Columbia, United States, 20016
  • Florida
    • Bradenton, Florida, United States
    • Doral, Florida, United States
    • Hialeah, Florida, United States, 33016
    • Homestead, Florida, United States, 33030
    • Orange City, Florida, United States, 32763
    • Tampa, Florida, United States, 33613
  • Illinois
    • Chicago, Illinois, United States, 60612
    • Chicago, Illinois, United States, 60640
    • Oak Brook, Illinois, United States, 60523
  • Indiana
    • Indianapolis, Indiana, United States, 46222
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
  • Mississippi
    • Flowood, Mississippi, United States, 39232
  • Missouri
    • Saint Louis, Missouri, United States, 63109
  • Nebraska
    • North Platte, Nebraska, United States, 69101
  • New York
    • Buffalo, New York, United States, 14215
    • New York, New York, United States, 10035
    • Queens, New York, United States
    • Rochester, New York, United States, 14615
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
  • Ohio
    • Akron, Ohio, United States
    • Canton, Ohio, United States, 44718
    • Toledo, Ohio, United States, 43609
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
    • Jenkintown, Pennsylvania, United States, 19046
    • Sellersville, Pennsylvania, United States, 18960
  • South Carolina
    • Charleston, South Carolina, United States, 29401
  • Tennessee
    • Memphis, Tennessee, United States, 38119
  • Texas
    • Austin, Texas, United States, 78731
    • Austin, Texas, United States, 78754
    • DeSoto, Texas, United States, 75115
  • Virginia
    • Richmond, Virginia, United States, 23230
  • Washington
    • Bothell, Washington, United States, 98011
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226

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:

• Participants with a current diagnosis of schizophrenia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, who completed the open-label extension Study 248 (completed Study 248 study completion visit, Week 52).
• Participants who, in the investigator's judgment, may benefit from continued participation in an aripiprazole IM Depot study.
• The baseline visit for Study 270 (which is the Week 52 visit of Study 248) and the first injection for Study 270 must occur within 4 weeks (which was defined as 28 [-2/+10] days) of the last injection in Study 248.
• Participants who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by an Independent Review Board/Independent Ethics Committee (IRB/IEC), prior to the initiation of any protocol-required procedures.
• Participants able to understand the nature of the study and follow protocol requirements and who can read and understand the written word in order to complete patient-reported outcomes measures.
• Outpatient status.

Exclusion Criteria:

• Participants with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic, or other cognitive disorders.
• Participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
• Participants who currently meet DSM-IV-TR criteria for substance dependence, including alcohol and benzodiazepines, but excluding caffeine and nicotine.
• Participants with a significant risk of violent behavior or a significant risk of committing suicide based on the investigator's judgment.
• Participants who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.
• Participants with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia at screening.
• Electroconvulsive therapy within 180 days prior to entry.
• Any participant who requires or may need any other antipsychotic medications during the course of the study.
• Aripiprazole IM Depot (including generic formulation) is commercially available in the participant's country.
• Other protocol specific inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole IM depot; Active treatment of monthly doses of aripiprazole IM depot (300 mg or 400 mg)	Drug: Aripiprazole; Aripiprazole IM depot - 300 mg or 400 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Of Participants Reporting Severe Treatment-Emergent Adverse Events (TEAE)	A TEAE was defined as an AE that started after start of investigational medicinal product (IMP) treatment or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption, or reduction of IMP. A severe AE was one that caused inability to work or perform normal daily activity. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Baseline to Month 97 (+/- 3 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change In Clinical Global Impression-Severity (CGI-S) of Illness Scale Score From Baseline To Last Visit	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. The Last Visit was defined as the last available post-baseline evaluation. A decrease in the CGI-S score indicated disease stability or improvement.	Baseline, Month 91

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2010
• Primary Completion (Actual): December 6, 2018
• Study Completion (Actual): December 6, 2018

Study Registration Dates

• First Submitted: May 22, 2010
• First Submitted That Met QC Criteria: May 22, 2010
• First Posted (Estimate): May 25, 2010

Study Record Updates

• Last Update Posted (Actual): January 6, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia
• 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: 31-10-270

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

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