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

NCT ID: NCT00705783

Last Updated: 2013-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 843 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2011-02-28

Brief Summary

The purpose of the trial was to evaluate the efficacy, safety, and tolerability of an intramuscular depot formulation of aripiprazole as maintenance treatment in patients with schizophrenia.

The trial was designed into 4 treatment phases. Phase 1 was designed to allow for a patient to be converted from their current antipsychotic treatment to oral non-generic aripiprazole monotherapy (oral conversion phase from 4 to 6 weeks). During Phase 2, the patient was stabilized on oral non-generic aripiprazole monotherapy (oral stabilization phase from a minimum of 4 weeks to a maximum of 12 weeks). Once the patient was stabilized in Phase 2, they entered Phase 3, the single-blind intramuscular (IM) depot aripiprazole stabilization phase. The goal of the phase was to stabilize the patient on the IM depot aripiprazole formulation for a minimum of 12 weeks to a maximum of 36 weeks. When the patient was stabilized, they were eligible to be randomized into the double-blind IM depot maintenance phase (Phase 4). During Phase 4, the patient was assessed for exacerbation of psychotic symptoms and/or impending relapse for up to 52 weeks.

Detailed Description

This was a randomized, double-blind, placebo-controlled study consisting of a screening phase and 4 treatment phases. Eligibility was determined during a screening phase of 2 to 42 days. Patients receiving oral treatment with an antipsychotic other than non-generic aripiprazole entered Phase 1. Patients with a lapse in aripiprazole or other antipsychotic treatment at the time of study entry ("lapse" defined as > 3 consecutive days without medication) entered directly into Phase 2. During Phase 1 (oral conversion), patients were cross-titrated during weekly visits from other antipsychotics to oral non-generic aripiprazole monotherapy over a minimum of 4 weeks and a maximum of 6 weeks. During Phase 2 (a minimum of 4 weeks and a maximum of 12 weeks in duration), patients were assessed bi-weekly and stabilized on an oral dose of aripiprazole ranging from 10 mg to 30 mg daily. After stability criteria were met in Phase 2, patients entered the single-blind aripiprazole intramuscular (IM) depot stabilization phase, Phase 3. In Phase 3, patients were stabilized on aripiprazole IM depot for 12 consecutive weeks. Once the patient met the stability criteria, they were eligible to be randomized into the double-blind phase, Phase 4. Patients were randomized in a 2:1 ratio (aripiprazole IM depot vs placebo IM depot) stratified by region and last aripiprazole IM depot injection dose level in Phase 3. During Phase 4, patients were assessed for impending relapse/exacerbation of psychotic symptoms. If a patient was identified with impending relapse/exacerbation of psychotic symptoms, they were withdrawn from the trial and given the opportunity to enroll into an open-label aripiprazole IM depot trial, 31-08-248. Patients that completed Phase 4 (up to and including Week 52) had the option to enroll into an open-label aripiprazole IM depot trial, 31-08-248 (NCT00731549).

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aripiprazole depot

Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.

Group Type: EXPERIMENTAL

Aripiprazole depot

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 depot

Patients received placebo intramuscularly every 28 days for 52 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo depot

Intervention Type: DRUG

Placebo depot was supplied in 400 mg lyophilized vials.

Interventions

Aripiprazole depot

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

Placebo depot

Placebo depot was supplied in 400 mg lyophilized vials.

Intervention Type: DRUG

Other Intervention Names

Abilify

Eligibility Criteria

Inclusion Criteria

• Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by the Institutional Review Board/Institutional 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, 4th edition 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 antipsychotic 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 outcomes 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, or 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 antipsychotic agents.
• 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 them to undue risk or interfere with study assessments.
• Subjects who are involuntary incarcerated.
• Subjects who have used an investigational agent within 30 days of screening or prior participation in a clinical study with aripiprazole IM depot.
• Subjects with clinically significant abnormalities in laboratory test results, vital signs, or ECG results; and subjects hospitalized for more than 30 days in the 90 days prior to Phase 1.
• 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/or Phase 1.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raymond Sanchez, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

Otsuka Investigational Site

Chandler, Arizona, United States

Otsuka Investigational Site

Anaheim, California, United States

Otsuka Investigational Site

National City, California, United States

Otsuka Investigational Site

Oceanside, California, United States

Otsuka Investigational Site

San Diego, California, United States

Otsuka Investigational Site

Santa Ana, California, United States

Otsuka Investigational Site

Highlands Ranch, Colorado, United States

Otsuka Investigational Site

Norwalk, Connecticut, United States

Otsuka Investigational Site

Altamonte Springs, Florida, United States

Otsuka Investigational Site

Bradenton, Florida, United States

Otsuka Investigational Site

Hollywood, Florida, United States

Otsuka Investigational Site

Maitland, Florida, United States

Otsuka Investigational Site

Miami, Florida, United States

Otsuka Investigational Site

North Miami, Florida, United States

Otsuka Investigational Site

Orange City, Florida, United States

Otsuka Investigational Site

Tampa, Florida, United States

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Atlanta, Georgia, United States

Otsuka Investigational Site

Hoffman Estates, Illinois, United States

Otsuka Investigational Site

Munster, Indiana, United States

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Baton Rouge, Louisiana, United States

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Baton Rouge, Louisiana, United States

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Lake Charles, Louisiana, United States

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New Orleans, Louisiana, United States

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Columbia, Maryland, United States

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Flowood, Mississippi, United States

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St Louis, Missouri, United States

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North Platte, Nebraska, United States

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Albuquerque, New Mexico, United States

Otsuka Investigational Site

Buffalo, New York, United States

Otsuka Investigational Site

Cedarhurst, New York, United States

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Elmsford, New York, United States

Otsuka Investigational Site

Holliswood, New York, United States

Otsuka Investigational Site

Jamaica, New York, United States

Otsuka Investigational Site

Staten Island, New York, United States

Otsuka Investigational Site

Cleveland, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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DeSoto, Texas, United States

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Bellevue, Washington, United States

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Bothell, Washington, United States

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Richland, Washington, United States

Otsuka Investigational Site

Ciudad Autónoma de Bs. As., Buenos Aires, Argentina

Otsuka Investigational Site

La Plata, Buenos Aires, Argentina

Otsuka Investigational Site

Lanús Este, Buenos Aires, Argentina

Otsuka Investigational Site

Córdoba, Córdoba Province, Argentina

Otsuka Investigational Site

Pueyrredón, Córdoba Province, Argentina

Otsuka Investigational Site

Mendoza, Mendoza Province, Argentina

Otsuka Investigational Site

Mendoza, Mendoza Province, Argentina

Otsuka Investigational Site

Rosario, Santa Fe Province, Argentina

Otsuka Investigational Site

Buenos Aires, , Argentina

Otsuka Investigational Site

Buenos Aires, , Argentina

Otsuka Investigational Site

Lovech, , Bulgaria

Otsuka Investigational Site

Pleven, , Bulgaria

Otsuka Investigational Site

Plovdiv, , Bulgaria

Otsuka Investigational Site

Radnevo, , Bulgaria

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Region of Veliko Tarnovo, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Ahmedabad, Gujarat, India

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Bangalore, Karnataka, India

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Chennai, Tamil Nadu, India

Otsuka Investigational Site

Kanpur, , India

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Mangalore, , India

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Pune, , India

Otsuka Investigational Site

Tirupati, , India

Otsuka Investigational Site

Cheras, Kuala Lumpur, Malaysia

Otsuka Investigational Site

Kuala Lumpur, Kuala Lumpur, Malaysia

Otsuka Investigational Site

Tanjong Rambutan, Perak, Malaysia

Otsuka Investigational Site

Kuala Selangor, , Malaysia

Otsuka Investigational Site

Guadalajara, Jalisco, Mexico

Otsuka Investigational Site

Mexico City, Mexico City, Mexico

Otsuka Investigational Site

Monterrey, Nuevo León, Mexico

Otsuka Investigational Site

San Luis Potosí City, San Luis Potosí, Mexico

Otsuka Investigational Site

Culiacán, Sinaloa, Mexico

Otsuka Investigational Site

Bataan, Central Luzon, Philippines

Otsuka Investigational Site

Mandaluyong, NCR, Philippines

Otsuka Investigational Site

Quezon City, NCR, Philippines

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Iloilo City, Western Visayas, Philippines

Otsuka Investigational Site

Cebu City, , Philippines

Otsuka Investigational Site

Arad, , Romania

Otsuka Investigational Site

Bucharest, , Romania

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Cluj-Napoca, , Romania

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Craiova, , Romania

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Oradea, , Romania

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Piteşti, , Romania

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Lipetsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Nizhny Novgorod, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Smolensk, , Russia

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Belgrade, , Serbia

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Kragujevac, , Serbia

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Košice, , Slovakia

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Liptovský Mikuláš, , Slovakia

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Prešov, , Slovakia

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Rimavská Sobota, , Slovakia

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Svidník, , Slovakia

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Changhua, , Taiwan

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Hualien City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

Otsuka Investigational Site

Taipei, , Taiwan

Countries

United States; Argentina; Bulgaria; India; Malaysia; Mexico; Philippines; Romania; Russia; Serbia; Slovakia; Taiwan

References

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.

Reference Type: RESULT

PMID: 22697189 (View on PubMed)

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, Johnson B, Jin N, Forbes RA, McQuade R, Baker RA, Carson W, Kane JM. Long-term safety and tolerability of aripiprazole once-monthly in maintenance treatment of patients with schizophrenia. Int Clin Psychopharmacol. 2013 Jul;28(4):171-6. doi: 10.1097/YIC.0b013e3283615dba.

Reference Type: DERIVED

PMID: 23615694 (View on PubMed)

Other Identifiers

31-07-246

Identifier Type: -

Identifier Source: org_study_id