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

Condition(s) targeted: Schizophrenia

Intervention: Intramuscular (IM) Depot Aripiprazole Formulation (Drug); Intramuscular (IM) Depot Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Otsuka Pharmaceutical Development & Commercialization, Inc.

Official(s) and/or principal investigator(s):
Mohammed Bari, MD, Principal Investigator, Affiliation: Synergy Clinical Research Center

Overall contact:
Clinical Contact Line, Phone: 1-866-670-3668

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 aripiprazole monotherapy. During Phase 2 the subject will be stabilized on oral aripiprazole monotherapy. 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. 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 52 weeks.

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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: 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.

Secondary outcome:

Mean change from baseline to endpoint in PANSS Total Score

Mean change from baseline to endpoint in the PSP Scale

Mean change from baseline to endpoint in CGI-S

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 aripiprazole will enter Phase 1. During Phase 1 (oral conversion), subjects will be cross-titrated during weekly visits from other antipsychotics to oral 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.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

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.

- 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.

- Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment

with aripiprazole or other quinolinones.

- Subjects with a history of hypersensitivity to antipsychotic agents.

Clinical Contact Line, Phone: 1-866-670-3668

Synergy Clinical Research Center, National City, California, United States; Recruiting

Starting date: July 2008
Ending date: August 2012
Last updated: December 31, 2008