Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia - Full Text View

Sponsor:	Otsuka Pharmaceutical Development & Commercialization, Inc.
Information provided by (Responsible Party):	Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:	NCT00705783

Purpose

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

The trial is designed into four treatment phases. Phase 1 is designed to allow for a subject to be converted from the current antipsychotic 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 (oral stabilization phase from minimum 4 weeks to maximum 12 weeks). Once the subject is stabilized in Phase 2 they will enter Phase 3, the single-blind IM depot aripiprazole stabilization phase. The goal of the phase is to stabilize the subject on the IM depot aripiprazole formulation for a minimum 12 weeks to maximum 36 weeks. When the subject is stabilized, they would be eligible to be randomized into the double-blind IM depot maintenance phase (Phase 4). During Phase 4, the subject will be assessed for exacerbation of psychotic symptoms and impending relapse for up to 52 weeks.

Condition	Intervention	Phase
Schizophrenia	Drug: Intramuscular (IM) Depot Aripiprazole Formulation Drug: Intramuscular (IM) Depot Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of an Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia

Resource links provided by NLM:

MedlinePlus related topics: Mental Disorders Psychotic Disorders Schizophrenia

Drug Information available for: Aripiprazole

U.S. FDA Resources

Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:

The primary efficacy endpoint of this study is time to exacerbation of psychotic symptoms/impending relapse, in schizophrenic patients who have maintained stability on aripiprazole IM depot for at least 12 weeks. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean change from baseline to endpoint in PANSS Total Score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percentage of subjects meeting exacerbation of psychotic symptoms/impending relapse criteria [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Mean change from baseline to endpoint in CGI-S [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
AEs will be examined by frequency, severity, seriousness, and discontinuation from study due to AEs. [ Time Frame: 138 weeks ] [ Designated as safety issue: Yes ]
Suicidality will be summarized by change from baseline in CGI-SS (Part 1) and mean CGI-SS score (Part 2) [ Time Frame: 12 weeks, 36 weeks and 52 weeks ] [ Designated as safety issue: Yes ]
Injection site pain will be evaluated by mean VAS scores as reported by the subject before and after each injection and at each study visit. [ Time Frame: 36 weeks, and 52 weeks ] [ Designated as safety issue: Yes ]
The incidence of clinically significant changes will be calculated for vital signs and routine laboratory tests. [ Time Frame: 106 weeks ] [ Designated as safety issue: Yes ]
The investigator rating of localized pain, redness, swelling, and induration at the injection site will also be tabulated for pre- and post-injection site evaluations at each visit [ Time Frame: 36 weeks and 52 weeks ] [ Designated as safety issue: Yes ]
Mean change from baseline and incidence of clinically significant changes will be calculated for ECG parameters, prolactin concentrations, and body weight. [ Time Frame: 106 weeks ] [ Designated as safety issue: Yes ]
EPS will be evaluated by calculating mean change from baselines in SAS, AIMS, and BARS. [ Time Frame: 106 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	1025
Study Start Date:	July 2008
Study Completion Date:	February 2011
Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Active Comparator: Treatment of Aripiprazole IM Depot	Drug: Intramuscular (IM) Depot Aripiprazole Formulation Intramuscular (IM) Depot Aripiprazole Formulation 400 mg or 300 mg, once a month injection
Placebo Comparator: 2 Placebo Comparator: Treatment of IM Depot Placebo	Drug: Intramuscular (IM) Depot Placebo Intramuscular (IM) Depot Placebo 400 mg or 300 mg, once a month injection

Detailed Description:

This will be a randomized, double-blind, placebo-controlled study consisting of a screening phase and four treatment phases. Eligibility will be determined during a screening phase of 2 to 42 days. Subjects currently receiving oral treatment with an antipsychotic other than non-generic aripiprazole will enter Phase 1. Subjects with a lapse in aripiprazole or other antipsychotic 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 antipsychotics 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 4 weeks and a maximum of 12 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 will enter the single-blind aripiprazole IM depot stabilization phase, Phase 3. At Phase 3 subjects will need to be stabilized on aripiprazole IM depot for 6 consecutive visits. Once the subjects meet the stability criteria, they are eligible to be randomized into the double-blind phase, Phase 4. Subjects will be randomized with a 2:1 ratio (aripiprazole IM depot vs placebo IM depot). During Phase 4, 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. Alternatively, subjects that complete Phase 4 (up to and including week-52) will have the option to enroll into an open-label aripiprazole IM depot trial, 31-08-248.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as require by 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 DSM-IV-TR criteria and a history of the illness for at least three 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, 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 two 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; 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, 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 MAOIs), and mood stabilizers during screening and/or Phase 1.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705783

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Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

More Information

No publications provided

Responsible Party:	Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:	NCT00705783 History of Changes
Other Study ID Numbers:	31-07-246
Study First Received:	June 24, 2008
Last Updated:	September 2, 2011
Health Authority:	United States: Food and Drug Administration; India: Drugs Controller General of India; Taiwan: Department of Health; Romania: Ministry of Public Health; Slovakia: State Institute for Drug Control; Malaysia: Ministry of Health; Bulgaria: Ministry of Health; Russia: Pharmacological Committee, Ministry of Health; Philippines: Department of Health; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica; Serbia and Montenegro: Agency for Drugs and Medicinal Devices; Mexico: Federal Commission for Sanitary Risks Protection

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Aripiprazole
Intramuscular (IM) Depot
Schizophrenia

Additional relevant MeSH terms:

Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Aripiprazole
Antipsychotic Agents
Tranquilizing Agents

Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on February 09, 2012