Clinical trial NCT00706654: Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia
Official title: A 38-week, Multicenter, Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of an Intramuscular Depot Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Aripiprazole
Intramuscular (IM) depot
Schizophrenia
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2008-06-27
Enrollment: 937
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

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 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.

Primary outcomes:
measure: Percentage of Patients Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria by the End of Week 26
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Time to Exacerbation of Psychotic Symptoms/Impending Relapse
timeFrame: Baseline to the end of the study (Week 38)
measure: Percentage of Responders up to Week 38
timeFrame: Baseline to the end of the study (Week 38)
measure: Percentage of Patients Achieving Remission
timeFrame: Baseline to the end of the study (Week 38)
Other outcomes:
Locations:
city: Cerritos
country: United States
state: California
city: Escondido
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Orange
country: United States
state: California
city: Orange
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Pico Rivera
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: Torrance
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Oak Brook
country: United States
state: Illinois
city: Shreveport
country: United States
state: Louisiana
city: Towson
country: United States
state: Maryland
city: Kansas City
country: United States
state: Missouri
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: South Carolina
country: United States
state: North Carolina
city: Garfield Heights
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Charleston
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: Johnson City
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Innsbruck
country: Austria
city: Brugge
country: Belgium
city: Bourgas
country: Bulgaria
city: Pazardjik
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Valdivia
country: Chile
city: Zagreb
country: Croatia
city: Zagreb
country: Croatia
city: Jamejala
country: Estonia
state: Viljandi County
city: Meegomäe
country: Estonia
city: Tallinn
country: Estonia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Tartu
country: Estonia
city: Bully Les Mines
country: France
city: Elancourt
country: France
city: Rennes
country: France
city: Saint Nazaire
country: France
city: Baja
country: Hungary
city: Balassagyarmat
country: Hungary
city: Cegléd
country: Hungary
city: Győőor
country: Hungary
city: Milano
country: Italy
city: Milano
country: Italy
city: Pisa
country: Italy
city: Busan
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Belchatow
country: Poland
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Choroszcz
country: Poland
city: Krakow
country: Poland
city: Leszno
country: Poland
city: Pruszków
country: Poland
city: Sosnowiec
country: Poland
city: Wroclaw
country: Poland
city: San Juan
country: Puerto Rico
city: Pretoria
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Province
city: Muang
country: Thailand
state: Chiangmai
city: Muang
country: Thailand
state: Chiangmai
city: Bangkok
country: Thailand
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Raymond Sanchez, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.