Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia

NCT ID: NCT00706654

Last Updated: 2013-08-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

937 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2012-08-31

Brief Summary

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The purpose of the this trial is to evaluate the efficacy, safety, and tolerability of an intramuscular (IM) depot formulation of aripiprazole as maintenance treatment in patients with schizophrenia

The trial is designed into three treatment phases. Phase 1 is designed to allow for a subject to be converted from the current anti-psychotic treatment to oral non-generic aripiprazole monotherapy (oral conversion phase from 4 to 6 weeks). During Phase 2 the subject will be stabilized on oral non-generic aripiprazole monotherapy. Once the subject is stabilized in Phase 2 (oral stabilization phase from minimum 8 weeks to maximum 28 weeks), they are eligible to be randomized into the double-blind IM depot maintenance phase, Phase 3. During Phase 3, the subject will be assessed for exacerbation of psychotic symptoms and impending relapse for up to 38 weeks.

Detailed Description

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This will be a randomized, double-blind, active-controlled study consisting of a screening phase and 3 treatment phases. Eligibility will be determined during a screening phase of 2 to 42 days. Subjects currently receiving oral treatment with an anti-psychotic other than non-generic aripiprazole will enter Phase 1, and subjects with a lapse in aripiprazole or other anti-psychotic treatment at the time of study entry ("lapse" defined as \> 3 consecutive days without medication) will enter directly into Phase 2.

During Phase 1 (oral conversion), subjects will be cross-titrated during weekly visits from other anti-psychotics to oral non-generic aripiprazole monotherapy over a minimum of 4 weeks and a maximum of 6 weeks. During Phase 2 (that will be a minimum of 8 weeks and a maximum of 28 weeks in duration), subjects will be assessed bi-weekly and stabilized on an oral dose of aripiprazole ranging from 10 mg to 30 mg daily. After stability criteria are met at Phase 2, subjects are eligible to be randomized into the double-blind IM depot maintenance phase, Phase 3. Subjects will be randomized with a 2:2:1 (aripiprazole IM depot 300-400 mg monthly, oral aripiprazole 10-30 mg daily, aripiprazole IM depot 25-50 mg monthly). During Phase 3 subjects will be assessed for impending relapse/exacerbation of psychotic symptoms. If a subject is identified with impending relapse/exacerbation of psychotic symptoms, they will be withdrawn from the trial and given the opportunity to enroll into an open-label aripiprazole IM depot trial, 31-08-248 (NCT00731549). Alternatively, any subject that discontinues in Phase 3 (up to and including Week 38) will have the option to enroll into an open-label aripiprazole IM depot trial, 31-08-248 (NCT00731549).

The enrollment figure includes re-screened patients.

Conditions

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Schizophrenia

Keywords

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Aripiprazole Intramuscular (IM) depot Schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Aripiprazole depot 300 or 400 mg

Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 38 weeks.

Group Type EXPERIMENTAL

Aripiprazole depot 300 or 400 mg

Intervention Type DRUG

Aripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg.

Placebo tablets

Intervention Type DRUG

Placebo tablets were identical in appearance to the aripiprazole tablets.

Aripiprazole 10-30 mg orally

Patients received aripiprazole 10-30 mg orally daily for 38 weeks.

Group Type ACTIVE_COMPARATOR

Aripiprazole 10-30 mg orally

Intervention Type DRUG

Aripiprazole was supplied as 10, 15, and 20 mg tablets. The dose that the patient received was based on the investigator's judgment and the subject's clinical need.

Placebo depot

Intervention Type DRUG

Placebo depot was supplied in lyophilized vials.

Aripiprazole depot 25 or 50 mg

Patients received aripiprazole 25 mg or 50 mg depot intramuscularly every 28 days for 38 weeks.

Group Type EXPERIMENTAL

Aripiprazole depot 25 or 50 mg

Intervention Type DRUG

Aripiprazole depot was supplied in 200 mg lyophilized vials. Patients received aripiprazole 25 mg if they were unable to tolerate aripiprazole 50 mg.

Placebo tablets

Intervention Type DRUG

Placebo tablets were identical in appearance to the aripiprazole tablets.

Interventions

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Aripiprazole depot 300 or 400 mg

Aripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg.

Intervention Type DRUG

Aripiprazole 10-30 mg orally

Aripiprazole was supplied as 10, 15, and 20 mg tablets. The dose that the patient received was based on the investigator's judgment and the subject's clinical need.

Intervention Type DRUG

Aripiprazole depot 25 or 50 mg

Aripiprazole depot was supplied in 200 mg lyophilized vials. Patients received aripiprazole 25 mg if they were unable to tolerate aripiprazole 50 mg.

Intervention Type DRUG

Placebo depot

Placebo depot was supplied in lyophilized vials.

Intervention Type DRUG

Placebo tablets

Placebo tablets were identical in appearance to the aripiprazole tablets.

Intervention Type DRUG

Other Intervention Names

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Abilify Abilify Abilify

Eligibility Criteria

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Inclusion Criteria

* Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by Institutional Review Board/Independent Ethics Committee \[IRB/IEC\]), prior to the initiation of any protocol-required procedures.
* Male and female subjects 18 to 60 years of age, inclusive, at time of informed consent.
* Subjects with a current diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, version 4, Text Revision (DSM-IV-TR) criteria and a history of the illness for at least 3 years prior to screening.
* Subjects who, in the investigator's judgment, require chronic treatment with an anti-psychotic medication.
* Subjects able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, IM depot injection, discontinuation of prohibited concomitant medications, who can read and understand the written word in order to complete patient-reported outcome measures, and who can be reliably rated on assessment scales.

Exclusion Criteria

* Subjects 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. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
* Subjects with schizophrenia that are considered resistant/refractory to antipsychotic treatment by history or response only to clozapine.
* Subjects with a significant risk of violent behavior or a significant risk of committing suicide based on history or investigator's judgment.
* Subjects who currently meet DSM-IV-TR criteria for substance dependence; including alcohol and benzodiazepines, but excluding caffeine and nicotine, or 2 positive drug screens for cocaine.
* Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones, or hypersensitivity to anti-psychotic agents, including aripiprazole.
* Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia at screening.
* Subjects with uncontrolled thyroid function abnormalities.
* Subjects with a history of seizures, neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or other medical condition that would expose the subject to undue risk or interfere with study assessments.
* Subjects who are involuntarily incarcerated.
* Subjects who have undergone electroconvulsive therapy within 180 days of entry into Phase 2.
* Subjects who have used an investigational agent within 30 days of screening; and prior participation in a clinical study with aripiprazole IM depot.
* Subjects with clinically significant abnormalities in laboratory test results, vital signs, or ECG results.
* Subjects hospitalized for more than 30 days in the 90 days prior to Phase 1 (or Phase 2 for subjects bypassing Phase 1).
* Subjects requiring more than 1 benzodiazepine beyond screening (eg, lorazepam and oxazepam).
* Subjects who fail to wash-out from prohibited concomitant medications, including the use of CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers, antipsychotics, antidepressants (including monoamine oxidase inhibitors \[MAOI\]), and mood stabilizers, during screening and Phase 1.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raymond Sanchez, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

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Cerritos, California, United States

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Escondido, California, United States

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Garden Grove, California, United States

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Oceanside, California, United States

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Orange, California, United States

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Orange, California, United States

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Pasadena, California, United States

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Pico Rivera, California, United States

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San Diego, California, United States

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San Diego, California, United States

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San Diego, California, United States

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Torrance, California, United States

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Washington D.C., District of Columbia, United States

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Gainesville, Florida, United States

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Kissimmee, Florida, United States

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Plantation, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Oak Brook, Illinois, United States

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Shreveport, Louisiana, United States

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Towson, Maryland, United States

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Kansas City, Missouri, United States

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Buffalo, New York, United States

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New York, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Hickory, North Carolina, United States

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South Carolina, North Carolina, United States

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Garfield Heights, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Charleston, South Carolina, United States

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Charleston, South Carolina, United States

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Johnson City, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Richmond, Virginia, United States

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Milwaukee, Wisconsin, United States

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Innsbruck, , Austria

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Bruges, , Belgium

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Burgas, , Bulgaria

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Pazardzhik, , Bulgaria

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Valdivia, , Chile

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Zagreb, , Croatia

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Zagreb, , Croatia

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Jämejala, Viljandimaa, Estonia

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Meegomäe, , Estonia

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Tallinn, , Estonia

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Tallinn, , Estonia

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Tartu, , Estonia

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Tartu, , Estonia

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Bully-les-Mines, , France

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Élancourt, , France

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Rennes, , France

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Saint-Nazaire, , France

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Baja, , Hungary

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Balassagyarmat, , Hungary

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Cegléd, , Hungary

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Győőor, , Hungary

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Milan, , Italy

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Milan, , Italy

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Pisa, , Italy

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Bełchatów, , Poland

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Choroszcz, , Poland

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Krakow, , Poland

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Leszno, , Poland

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Pruszków, , Poland

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Sosnowiec, , Poland

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Wroclaw, , Poland

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San Juan, , Puerto Rico

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Pretoria, Gauteng, South Africa

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Cape Town, Western Province, South Africa

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Busan, , South Korea

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Daejeon, , South Korea

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Gwangju, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Muang, Chiangmai, Thailand

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Muang, Chiangmai, Thailand

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Bangkok, , Thailand

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Countries

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Brazil China Czechia Germany Israel Spain United States Austria Belgium Bulgaria Chile Croatia Estonia France Hungary Italy Poland Puerto Rico South Africa South Korea Thailand

References

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Kane JM, Sanchez R, Baker RA, Eramo A, Peters-Strickland T, Perry PP, Johnson BR, Tsai LF, Carson WH, McQuade RD, Fleischhacker WW. Patient-Centered Outcomes with Aripiprazole Once-Monthly for Maintenance Treatment in Patients with Schizophrenia: Results From Two Multicenter, Randomized, Double-Blind Studies. Clin Schizophr Relat Psychoses. 2015 Summer;9(2):79-87. doi: 10.3371/CSRP.KASA.022015. Epub 2015 Feb 24.

Reference Type DERIVED
PMID: 25711509 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24925984 (View on PubMed)

Other Identifiers

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31-07-247

Identifier Type: -

Identifier Source: org_study_id