SchizophreniaPhase 3ASPIRENCT00705783
Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia
A Phase 3 study testing Aripiprazole depot in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 110 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Aripiprazole depot
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 843 participants
- Where
- 110 sitesin 12 countries
- Study dates
- Jul 2008to Feb 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
110 sites in 12 countries.
110 sites in 12 countries
United States43 sites
Otsuka Investigational Site
Albuquerque, New Mexico, 87131
Otsuka Investigational Site
Altamonte Springs, Florida, 32701
Otsuka Investigational Site
Anaheim, California, 92805
Otsuka Investigational Site
Atlanta, Georgia, 30328
Otsuka Investigational Site
Austin, Texas, 78754
Otsuka Investigational Site
Baton Rouge, Louisiana, 70808
Otsuka Investigational Site
Baton Rouge, Louisiana, 70809
Otsuka Investigational Site
Bellevue, Washington, 98007
Otsuka Investigational Site
Bothell, Washington, 98011
Otsuka Investigational Site
Bradenton, Florida, 34208
Otsuka Investigational Site
Buffalo, New York, 14215
Otsuka Investigational Site
Cedarhurst, New York, 11516
Otsuka Investigational Site
Chandler, Arizona, 85226
Otsuka Investigational Site
Cleveland, Ohio, 44109
Otsuka Investigational Site
Columbia, Maryland, 21045
Otsuka Investigational Site
DeSoto, Texas, 75115
Otsuka Investigational Site
Elmsford, New York, 10523
Otsuka Investigational Site
Flowood, Mississippi, 39232
Otsuka Investigational Site
Highlands Ranch, Colorado, 80130
Otsuka Investigational Site
Hoffman Estates, Illinois, 60169
Otsuka Investigational Site
Holliswood, New York, 11423
Otsuka Investigational Site
Hollywood, Florida, 33021
Otsuka Investigational Site
Jamaica, New York, 11418
Otsuka Investigational Site
Lake Charles, Louisiana, 70601
Otsuka Investigational Site
Maitland, Florida, 32751
Otsuka Investigational Site
Memphis, Tennessee, 38119
Otsuka Investigational Site
Miami, Florida, 33135
Otsuka Investigational Site
Munster, Indiana, 46321
Otsuka Investigational Site
National City, California, 91950
Otsuka Investigational Site
New Orleans, Louisiana, 70115
Otsuka Investigational Site
North Miami, Florida, 33161
Otsuka Investigational Site
North Platte, Nebraska, 69101
Otsuka Investigational Site
Norwalk, Connecticut, 06851
Otsuka Investigational Site
Oceanside, California, 92056
Otsuka Investigational Site
Oklahoma City, Oklahoma, 73103
Otsuka Investigational Site
Orange City, Florida, 32763
Otsuka Investigational Site
Philadelphia, Pennsylvania, 19131
Otsuka Investigational Site
Richland, Washington, 99354
Otsuka Investigational Site
San Diego, California, 92123
Otsuka Investigational Site
Santa Ana, California, 92701
Otsuka Investigational Site
St Louis, Missouri, 63118
Otsuka Investigational Site
Staten Island, New York, 10305
Otsuka Investigational Site
Tampa, Florida, 33613
Argentina10 sites
Otsuka Investigational Site
Buenos Aires, C1405BOA
Otsuka Investigational Site
Buenos Aires, C1425AHQ
Otsuka Investigational Site
Ciudad Autónoma de Bs. As., Buenos Aires, C1058AAJ
Otsuka Investigational Site
Córdoba, Córdoba Province, X5009BIN
Otsuka Investigational Site
La Plata, Buenos Aires, 1900
Otsuka Investigational Site
Lanús Este, Buenos Aires, B1834IBR
Otsuka Investigational Site
Mendoza, Mendoza Province, 5500HYF
Otsuka Investigational Site
Mendoza, Mendoza Province, 5500
Otsuka Investigational Site
Pueyrredón, Córdoba Province, X5004ALB
Otsuka Investigational Site
Rosario, Santa Fe Province, 2000
Russia10 sites
Otsuka Investigational Site
Lipetsk, 399083
Otsuka Investigational Site
Moscow, 115409
Otsuka Investigational Site
Moscow, 115522
Otsuka Investigational Site
Moscow, 127473
Otsuka Investigational Site
Nizhny Novgorod, 603107
Otsuka Investigational Site
Nizhny Novgorod, 603155
Otsuka Investigational Site
Saint Petersburg, 188357
Otsuka Investigational Site
Saint Petersburg, 190121
Otsuka Investigational Site
Saint Petersburg, 192019
Otsuka Investigational Site
Smolensk, 214019
Bulgaria8 sites
Otsuka Investigational Site
Lovech, 5500
Otsuka Investigational Site
Pleven, 5800
Otsuka Investigational Site
Plovdiv, 4002
Otsuka Investigational Site
Radnevo, 6260
Otsuka Investigational Site
Region of Veliko Tarnovo, 5047
Otsuka Investigational Site
Rousse, 7000
Otsuka Investigational Site
Sofia, 1113
Otsuka Investigational Site
Varna, 9010
India7 sites
Otsuka Investigational Site
Ahmedabad, Gujarat, 380006
Otsuka Investigational Site
Bangalore, Karnataka, 560010
Otsuka Investigational Site
Chennai, Tamil Nadu, 600003
Otsuka Investigational Site
Kanpur, 208005
Otsuka Investigational Site
Mangalore, 575018
Otsuka Investigational Site
Pune, 411004
Otsuka Investigational Site
Tirupati, 517507
Romania6 sites
Otsuka Investigational Site
Arad, 310022
Otsuka Investigational Site
Bucharest, 041914
Otsuka Investigational Site
Cluj-Napoca, 400012
Otsuka Investigational Site
Craiova, 200620
Otsuka Investigational Site
Oradea, 410154
Otsuka Investigational Site
Piteşti, 110069
Mexico5 sites
Otsuka Investigational Site
Culiacán, Sinaloa, 80020
Otsuka Investigational Site
Guadalajara, Jalisco, 44280
Otsuka Investigational Site
Mexico City, Mexico City, 6700
Otsuka Investigational Site
Monterrey, Nuevo León, 64040
Otsuka Investigational Site
San Luis Potosí City, San Luis Potosí, 78218
Philippines5 sites
Otsuka Investigational Site
Bataan, Central Luzon, 2105
Otsuka Investigational Site
Cebu City, 6000
Otsuka Investigational Site
Iloilo City, Western Visayas, 5000
Otsuka Investigational Site
Mandaluyong, NCR, 1553
Otsuka Investigational Site
Quezon City, NCR, 1104
Slovakia5 sites
Otsuka Investigational Site
Košice, 041 90
Otsuka Investigational Site
Liptovský Mikuláš, 031 23
Otsuka Investigational Site
Prešov, 081 81
Otsuka Investigational Site
Rimavská Sobota, 979 12
Otsuka Investigational Site
Svidník, 089 01
Taiwan5 sites
Otsuka Investigational Site
Changhua, 500
Otsuka Investigational Site
Hualien City, 981
Otsuka Investigational Site
Tainan, 704
Otsuka Investigational Site
Taipei, 110
Otsuka Investigational Site
Taipei, 112
Malaysia4 sites
Otsuka Investigational Site
Cheras, Kuala Lumpur, 56000
Otsuka Investigational Site
Kuala Lumpur, Kuala Lumpur, 50603
Otsuka Investigational Site
Kuala Selangor, 43000
Otsuka Investigational Site
Tanjong Rambutan, Perak, 31250
Serbia2 sites
Otsuka Investigational Site
Belgrade, 11000
Otsuka Investigational Site
Kragujevac, 34000
About this study
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
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.
Read the 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
- Being tested
- Aripiprazole depot, Placebo depot
- Keywords
- Aripiprazole, Intramuscular (IM) depot, Schizophrenia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aripiprazole depotDrug
Also called Abilify
Aripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg.
Placebo depotDrug
Placebo depot was supplied in 400 mg lyophilized vials.
| Study group | Role | What they receive |
|---|---|---|
| Aripiprazole depot | Experimental | Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks. Receives: Drug: Aripiprazole depot |
| Placebo depot | Placebo comparator | Patients received placebo intramuscularly every 28 days for 52 weeks. Receives: Drug: Placebo depot |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Exacerbation of Psychotic Symptoms/Impending Relapse
A patient experienced an exacerbation of psychotic symptoms/impending relapse if they met any of the following 4 criteria. 1) Clinical Global Impression of Improvement score ≥ 5 and either an increase on any of the following Positive and Negative Syndrome Scale (PANSS) items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score > 4 with an increase of ≥ 2 on that item since randomization or an increase on any of the same PANSS items to a score > 4 and an increase of ≥ 4 on the same combined PANSS items since randomization, 2) Hospitalization due to worsening of psychotic symptoms, 3) Clinical Global Impression of Severity of Suicide (CGI-SS) score of 4 or 5 on Part 1 and/or 6 or 7 on Part 2, or 4) Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Secondary outcomes (9)
Percentage of Patients Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria
This is the key secondary Outcome Measure.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Percentage of Responders
A patient was considered to be a responder if all of the following criteria were met. 1) Outpatient status, 2) PANSS total score ≤ 80, 3) Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): Conceptual disorganization, suspiciousness, hallucinatory behavior, unusual thought content, and 4) Clinical Global Impression of Severity of Illness (CGI-S) ≤ 4 (moderately ill) and 5) CGI-SS ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Percentage of Patients Achieving Remission
A patient was considered to have achieved remission if they had a score of ≤ 3 on each of the following PANSS items, maintained for a period of 6 months: Delusions (P1), unusual thought content (G9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (N1), social withdrawal (N4), and lack of spontaneity (N6).
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the PANSS Total Score
The PANSS consists of 3 subscales (Positive Subscale, 7 constructs, scores ranged from 7-49, Negative Subscale, 7 constructs, scores ranged from 7-49, General Psychopathology Subscale, 16 constructs, scores ranged from 16-112) containing a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30-210 with a higher score indicating more severe symptoms. A negative change score indicates improvement.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score
The severity of illness for each patient was rated using the CGI-S. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. The CGI-S score ranged from 0-7 with a higher score indicating greater illness. A negative change score indicates improvement.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the PANSS Positive Subscale Score
The PANSS Positive Subscale consists of 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Scores on each subscale ranged from 7-49 with a higher score indicating more severe symptoms. A negative change score indicates improvement.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the PANSS Negative Subscale Score
The PANSS Negative Subscale consists of 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Scores on each subscale ranged from 7-49 with a higher score indicating more severe symptoms. A negative change score indicates improvement.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Clinical Global Impression-Improvement (CGI-I) Score
The efficacy of the study medication was rated for each patient using the CGI-I scale. The rater or investigator rated the patient's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the patient's condition at Baseline. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The CGI-I score ranged from 0-7 with a higher score indicating less improvement/worsening.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Time to Discontinuation
Time to discontinuation was defined as the date of randomization to the date of study discontinuation.
Measured: Baseline of the depot maintenance phase to the end of the study (Week 52)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2008 (estimated)
- Study startJul 2008
- Primary completionAug 2010
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 843 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Raymond Sanchez, MD, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00705783
- Sponsor's protocol ID
- 31-07-246
- Acronym
- ASPIRE
- Status last verified
- Jun 2013
- First submitted
- 24 Jun 2008
- Last updated
- 19 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22697189Citrome L, Bell Lynum KS, Zhang Z, Atkins N Jr, Hutson Walker AM, Yildirim M. Aripiprazole Once-Monthly for Patients Diagnosed With Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. J Clin Psychiatry. 2026 May 13;87(2):26m16359. doi: 10.4088/JCP.26m16359.
PubMed 42138587Kane 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. Epub 2015 Feb 24.
PubMed 25711509Fleischhacker 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.
PubMed 23615694
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00705783
- Acronym / sponsor ID
- ASPIRE / 31-07-246
- Conditions
- Schizophrenia
- Keywords
- Aripiprazole, Intramuscular (IM) depot, Schizophrenia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 843 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Aug 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 26 Jun 2008 (estimated)
- Results
- Posted 19 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aripiprazole depot | Experimental | Drug: Aripiprazole depotPatients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks. |
| Placebo depot | Placebo comparator | Drug: Placebo depotPatients received placebo intramuscularly every 28 days for 52 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aripiprazole depotAlso: AbilifyAripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg. | Drug | Aripiprazole depot |
| Placebo depotPlacebo depot was supplied in 400 mg lyophilized vials. | Drug | Placebo depot |
Primary outcome
Time to Exacerbation of Psychotic Symptoms/Impending Relapse
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
A patient experienced an exacerbation of psychotic symptoms/impending relapse if they met any of the following 4 criteria. 1) Clinical Global Impression of Improvement score ≥ 5 and either an increase on any of the following Positive and Negative Syndrome Scale (PANSS) items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score > 4 with an increase of ≥ 2 on that item since randomization or an increase on any of the same PANSS items to a score > 4 and an increase of ≥ 4 on the same combined PANSS items since randomization, 2) Hospitalization due to worsening of psychotic symptoms, 3) Clinical Global Impression of Severity of Suicide (CGI-SS) score of 4 or 5 on Part 1 and/or 6 or 7 on Part 2, or 4) Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage.
9 secondary outcomes
Percentage of Patients Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Percentage of Responders
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Percentage of Patients Achieving Remission
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the PANSS Total Score
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the PANSS Positive Subscale Score
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Change From Baseline in the PANSS Negative Subscale Score
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Mean Clinical Global Impression-Improvement (CGI-I) Score
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Time to Discontinuation
Time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22697189Kane 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.
- Derived from this study: PubMed 42138587Citrome L, Bell Lynum KS, Zhang Z, Atkins N Jr, Hutson Walker AM, Yildirim M. Aripiprazole Once-Monthly for Patients Diagnosed With Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. J Clin Psychiatry. 2026 May 13;87(2):26m16359. doi: 10.4088/JCP.26m16359.
- Derived from this study: PubMed 25711509Kane 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. Epub 2015 Feb 24.
- Derived from this study: PubMed 23615694Fleischhacker 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raymond Sanchez, MD study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
110 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aripiprazole depot in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 110 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 110 sites in United States, Argentina, Russia, Bulgaria, India and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Exacerbation of Psychotic Symptoms/Impending Relapse (time frame: Baseline of the depot maintenance phase to the end of the study (Week 52)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00705783, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2013.