Irritability Associated With Autistic DisorderPhase 4NCT01227668
Long-term Maintenance Study of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder
A Phase 4 study testing Aripiprazole in people with Irritability Associated With Autistic Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 38 sites in United States.
Trial summary
The purpose of this study is to determine whether pediatric participants with irritability associated with autistic disorder who have responded to aripiprazole treatment will experience a relapse significantly later when continuing therapy with aripiprazole than will participants who receive placebo. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Irritability Associated With Autistic Disorder
- What is being tested?
- Aripiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 215 participants
- Where
- 38 sitesUnited States
- Study dates
- 7 Mar 2011to 20 Jun 2012
- Phase
- Phase 4
- 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 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female children or adolescents, 6 to 17 years of age, inclusive, at the time of the baseline visit
- Meets current diagnostic criteria of the Diagnostic and Statistical Manual-of Mental Disorders IV-Text Revised for autistic disorder and displays behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these problems. Diagnosis of autistic disorder will be confirmed by the Autism Diagnostic Interview-Revised.
- Participant or designated guardian or caregiver is able to comprehend and satisfactorily comply with the protocol requirements, in the opinion of the investigator.
- Demonstrates behaviors such as tantrums, aggression, or self-injury or a combination of these problems
- An Aberrant Behavior Checklist Irritability subscale score ≥18 AND a Clinical Global Impressions Severity score ≥4 at the Screening and Baseline Visits.
- Mental age of at least 24 months
Who cannot join
- Treatment resistant to neuroleptic medication, based on lack of therapeutic response to 2 different neuroleptics after treatment for at least 3 weeks each.
- Previous treatment with aripiprazole for at least 3 weeks duration at an adequate daily dose, without demonstrating a clinically meaningful response.
- Lifetime diagnosis of bipolar disorder, psychosis, or schizophrenia, or a current diagnosis of major depressive disorder
- Diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified, Asperger's Syndrome, Rett's Syndrome, childhood disintegrative disorder, or Fragile X Syndrome
- History of neuroleptic malignant syndrome
- At significant risk for suicide based on history or routine psychiatric status examination
Show all 13Show fewer
- A seizure within the past year
- History of severe head trauma or stroke
- History or current evidence of any unstable medical conditions that would expose the patient to undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the course of the trial
- Weight lower than 15 kg
- Known allergy or hypersensitivity to aripiprazole or other dihidrocarbostyrils
- History of a clinically significant low white blood cell count or a drug-induced leukopenia/neutropenia
- Any other medically significant abnormal laboratory test or vital sign result or electrocardiogram finding
Trial locations and contacts
38 sites in 1 country.
38 sites in 1 country
United States38 sites
Neurobehavioral Medicine Group
Bloomfield Hills, Michigan, 48302
Unc Chapel Hill
Chapel Hill, North Carolina, 27517
Cleveland Clinic
Cleveland, Ohio, 44104
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Ericksen Research And Development
Clinton, Utah, 84015
Kootenai Behavioral Health Center
Coeur d'Alene, Idaho, 83814
The Ohio State University Nisonger Center
Columbus, Ohio, 43210
Clinical Innovations, Inc.
Costa Mesa, California, 92626
Insite Clinical Research
DeSoto, Texas, 75115
Harmonex Neuroscience Research, Inc
Dothan, Alabama, 36303
Sarkis Clinical Trials
Gainesville, Florida, 32607
Clinical Research Center Of New Jersey
Gibbsboro, New Jersey, 08026
Behavioral Research Specialists, Llc
Glendale, California, 91206
Cyn3rgy Research
Gresham, Oregon, 97030
Palm Springs Research Institute
Hialeah, Florida, 33012
Holston Medical Group
Kingsport, Tennessee, 37660
Center For Psychiatry And Behavioral Medicine, Inc
Las Vegas, Nevada, 89128
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, 40202
Florida Clinical Research Center, Llc
Maitland, Florida, 32751
Miami Children'S Hospital
Miami, Florida, 33155
Neurocare, Inc.
Newton, Massachusetts, 02459
Childrens Specialty Gr., Pllc
Norfolk, Virginia, 23510
Cutting Edge Research Group
Oklahoma City, Oklahoma, 73116
Ou Physician'S Child Study Center
Oklahoma City, Oklahoma, 73117
Abbey Neuropsychology Clinic
Palo Alto, California, 94306
Drexel University College Of Medicine
Philadelphia, Pennsylvania, 19124
Southwest Autism Research And Resource Center
Phoenix, Arizona, 85006
Western Psychiatric Institute And Clinic
Pittsburgh, Pennsylvania, 15203
Virginia Treatment Center For Children
Richmond, Virginia, 23298
Ucsf - Lppi
San Francisco, California, 94143
Lsu Health Sciences Center
Shreveport, Louisiana, 71103
Institute For Behavioral Medicine, Llc
Smyrna, Georgia, 30080
Stanford University School Of Medicine
Stanford, California, 94305
Stony Brook University School Of Medicine
Stony Brook, New York, 11794
University Of South Florida
Tampa, Florida, 33613
Children'S Specialized Hosp
Toms River, New Jersey, 08755
Tulsa Clinical Research, Llc
Tulsa, Oklahoma, 74104
Children'S National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Safety and Efficacy of Aripiprazole in the Long-term Maintenance Treatment of Pediatric Patients With Irritability Associated With Autistic Disorder
The purpose of this study is to determine whether pediatric participants with irritability associated with autistic disorder who have responded to aripiprazole treatment will experience a relapse significantly later when continuing therapy with aripiprazole than will participants who receive placebo.
- Being tested
- Aripiprazole, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AripiprazoleDrug
Also called BMS-337039, Abilify
Tablets, oral, 2-15 mg, once daily, 13-42 weeks
PlaceboDrug
Tablets, oral, 0 mg, once daily, 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Aripiprazole | Experimental | Not described Receives: Drug: Aripiprazole |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Relapsing by Week 16
Time of relapse=date when patient meets relapse criteria. There are 4 definitions for relapse: 1. Patient meets the following criteria for 2 consecutive visits: (a) Aberrant Behavior Checklist Irritability score ≥25% than score at end of Phase 1 AND (b) Clinical Global Impression Improvement scale rating of 'Much Worse' or 'Very Much Worse' relative to rating at end of Phase 1. If relapse criteria met at 1 visit, 2nd visit should occur in about 1 week to reevaluate whether relapse criteria are still met. 2. Patient discontinues for "Lost to Follow-up" after a visit in which he or she met Definition 1 criteria (a\&b). 3. Patient begins a prohibited drug (whether a study investigator or outside source prescribed) to treat worsening symptoms of irritability of autistic disorder after a visit where patient met Definition 1 criteria (a\&b). 4. Patient discontinues due to hospitalization for worsening symptoms of irritability or due to lack of efficacy based on investigator's assessment.
Measured: From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment
Secondary outcomes (3)
Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])
ABC is an informant-based checklist used to assess and classify problem behaviors of children and adolescents with mental retardation. The 58 items are rated on a 4-point scale (0=not at all a problem to 3=the problem is severe in degree), and resolve into 5 subscales: 1) irritability, agitation; 2) lethargy, social withdrawal; 3) stereotypic behavior; 4) hyperactivity, noncompliance; and 5) inappropriate speech. The ABC can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others knowing the participant. Psychometric assessment of the ABC indicates that its subscales have high internal consistency, adequate reliability, and established validity. The ABC-I Subscale Score ranges from 0 to 45, with a negative change in score signifying improvement. LOCF data set includes data recorded at a given visit or, if no observation was recorded at that visit, data carried forward from the prior visit. chg=change; BL=baseline; APR=aripiprazole; vs=versus.
Measured: From Baseline (end of Phase 1) to Week 16 of Phase 2
Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])
CG-I rating scale permits global evaluation of patient's improvement over time. At baseline (BL), CGI Severity of Illness assessment is performed, in which the clinician rates severity of patient's condition on a 7-point scale ranging from 1=no symptoms to 7=very severe symptoms. Higher total score=worse symptoms. At subsequent visits, clinician assesses patient's improvement relative to symptoms at baseline on CGI-I 7-point scale ranging from 1=very much improved to 7=very much worse. Since the drug targets irritability symptoms, the CGI focuses on severity of irritability secondary to autistic disorder. Lower score=more improved symptoms. LOCF data set includes data recorded at a given visit or, if nothing recorded, data areccarried forward from the prior visit. For secondary endpoints (endpt), hierarchical testing was used to keep overall experiment-wise type I error rate to <=0.05. diff=difference; IS=irritability scale; PA=primary analysis; signif=significance/significantly.
Measured: From Baseline (end of Phase 1) to Week 16 of Phase 2
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Measured: Up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study start7 Mar 2011
- Primary completion20 Jun 2012
- Study completion20 Jun 2012
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 (2)Papers the sponsor has linked to this study.
- Other trials for Irritability Associated With Autistic DisorderStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 215 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01227668
- Sponsor's protocol ID
- CN138-603
- Status last verified
- Oct 2026
- First submitted
- 22 Oct 2010
- Last updated
- 3 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711Findling RL, Mankoski R, Timko K, Lears K, McCartney T, McQuade RD, Eudicone JM, Amatniek J, Marcus RN, Sheehan JJ. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder. J Clin Psychiatry. 2014 Jan;75(1):22-30. doi: 10.4088/jcp.13m08500.
PubMed 24502859
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Aripiprazole in the Long-term Maintenance Treatment of Pediatric Patients With Irritability Associated With Autistic Disorder
- ClinicalTrials.gov ID
- NCT01227668
- Acronym / sponsor ID
- CN138-603
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Mar 2011 (actual)
- Primary completion
- 20 Jun 2012 (actual)
- Study completion
- 20 Jun 2012 (actual)
- First posted
- 25 Oct 2010 (estimated)
- Results
- Posted 2 May 2014
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 this study is to determine whether pediatric participants with irritability associated with autistic disorder who have responded to aripiprazole treatment will experience a relapse significantly later when continuing therapy with aripiprazole than will participants who receive placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aripiprazole | Experimental | Drug: Aripiprazole |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male or female children or adolescents, 6 to 17 years of age, inclusive, at the time of the baseline visit
- Meets current diagnostic criteria of the Diagnostic and Statistical Manual-of Mental Disorders IV-Text Revised for autistic disorder and displays behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these problems. Diagnosis of autistic disorder will be confirmed by the Autism Diagnostic Interview-Revised.
- Participant or designated guardian or caregiver is able to comprehend and satisfactorily comply with the protocol requirements, in the opinion of the investigator.
- Demonstrates behaviors such as tantrums, aggression, or self-injury or a combination of these problems
- An Aberrant Behavior Checklist Irritability subscale score ≥18 AND a Clinical Global Impressions Severity score ≥4 at the Screening and Baseline Visits.
Key exclusion criteria (13 listed)
- Treatment resistant to neuroleptic medication, based on lack of therapeutic response to 2 different neuroleptics after treatment for at least 3 weeks each.
- Previous treatment with aripiprazole for at least 3 weeks duration at an adequate daily dose, without demonstrating a clinically meaningful response.
- Lifetime diagnosis of bipolar disorder, psychosis, or schizophrenia, or a current diagnosis of major depressive disorder
- Diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified, Asperger's Syndrome, Rett's Syndrome, childhood disintegrative disorder, or Fragile X Syndrome
- History of neuroleptic malignant syndrome
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 |
|---|---|---|
| AripiprazoleAlso: BMS-337039, AbilifyTablets, oral, 2-15 mg, once daily, 13-42 weeks | Drug | Aripiprazole |
| PlaceboTablets, oral, 0 mg, once daily, 16 weeks | Drug | Placebo |
Primary outcome
Percentage of Patients Relapsing by Week 16
Time frame: From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment
Time of relapse=date when patient meets relapse criteria. There are 4 definitions for relapse: 1. Patient meets the following criteria for 2 consecutive visits: (a) Aberrant Behavior Checklist Irritability score ≥25% than score at end of Phase 1 AND (b) Clinical Global Impression Improvement scale rating of 'Much Worse' or 'Very Much Worse' relative to rating at end of Phase 1. If relapse criteria met at 1 visit, 2nd visit should occur in about 1 week to reevaluate whether relapse criteria are still met. 2. Patient discontinues for "Lost to Follow-up" after a visit in which he or she met Definition 1 criteria (a\&b). 3. Patient begins a prohibited drug (whether a study investigator or outside source prescribed) to treat worsening symptoms of irritability of autistic disorder after a visit where patient met Definition 1 criteria (a\&b). 4. Patient discontinues due to hospitalization for worsening symptoms of irritability or due to lack of efficacy based on investigator's assessment.
3 secondary outcomes
Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])
Time frame: From Baseline (end of Phase 1) to Week 16 of Phase 2
Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])
Time frame: From Baseline (end of Phase 1) to Week 16 of Phase 2
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1
Time frame: Up to 26 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
- Derived from this study: PubMed 24502859Findling RL, Mankoski R, Timko K, Lears K, McCartney T, McQuade RD, Eudicone JM, Amatniek J, Marcus RN, Sheehan JJ. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder. J Clin Psychiatry. 2014 Jan;75(1):22-30. doi: 10.4088/jcp.13m08500.
- Otsuka Clinical Trial WebsiteLink provided by the sponsor.
- Otsuka Clinical Trial TransparencyLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aripiprazole in people with Irritability Associated With Autistic Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 38 sites in United States.
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 6 inclusion and 13 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 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 2 May 2014). 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?
Percentage of Patients Relapsing by Week 16 (time frame: From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment). 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 NCT01227668, which also lists 2 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 3 Nov 2026.