Clinical trial NCT01149655: Efficacy & Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia
Official title: A Long-Term Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aripiprazole (OPC 14597) as Maintenance Treatment in Adolescent Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Adolescent
Schizophrenia
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2010-06-23
Enrollment: 252
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a randomized, double-blind, placebo-controlled study consisting of a screening period, a conversion phase (Phase 1), a stabilization phase (Phase 2), and a double-blind maintenance treatment phase (Phase 3), and a follow up period.

Subjects may be either outpatients or inpatients between screening and through the time they reach stabilization at the end of Phase 2; hospitalization is not a study requirement. However, eligible subjects must be outpatients at the beginning of Phase 3.

Subjects will be assessed weekly during Phase 1, weekly for the first 4 weeks of Phase 2 and 3, and biweekly for the remaining weeks during each of Phases 2 and 3. Subjects will be encouraged to call the investigators with any exacerbation of psychotic symptoms and/or any tolerability issues. The investigator will also have the option to phone the subjects and their guardian(s) at any time to ensure clinical stability.

A data monitoring committee (DMC) will provide oversight for safety monitoring and reviewing the interim analysis. One interim analysis is planned after 75% of the total expected number of impending relapse events (28 events) are achieved and will be conducted by an independent data analysis center. The DMC will make a recommendation about stopping or continuing the study based on safety and efficacy reviews. The results of the interim analysis and individual subject data will remain blinded to the sponsor during the course of the study until the DMC determines that the study will conclude based on the results of the interim analysis, or the study is completed after 37 endpoint events.


Eligibility criteria: Inclusion Criteria:

* Subjects with a current DSM-IV-TR diagnosis of schizophrenia, and a history of the illness (diagnosis or symptoms) for at least 6 months prior to screening.
* Subjects who have shown previous response to antipsychotic treatment (other than clozapine) and are not resistant to treatment with other antipsychotics.
* Subjects who are currently being treated with oral or depot antipsychotics other than clozapine.
* Subjects with a history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment.

Exclusion Criteria:

* Subjects with a current DSM-IV-TR diagnosis other than schizophrenia.
* Subjects with delirium, dementia, amnesia or other cognitive disorders; subjects with psychotic symptoms that are better accounted for by another general medical condition(s) or direct effect of a substance (i.e., medication, illicit drug use, etc.).
* Subjects with attention deficit disorder or attention deficit hyperactivity disorder and/or subjects who were on a stimulant treatment for any period of time over the last one year prior to screening.
* Subjects with any neurodevelopmental disorder, except Tourette's syndrome.
* Subjects experiencing acute depressive symptoms within the past 30 days prior to screening.
* Subjects who meet the DSM-IV-TR criteria for substance dependence (including alcohol and benzodiazepines, but excluding caffeine and nicotine) within the past 180 days prior to screening.
* Subjects who have epilepsy, a history of seizures (except for a single childhood febrile seizure or post-traumatic seizure), or a history of severe head trauma or stroke, or have a history or current evidence of other unstable medical conditions.
* Subjects with a history of subclinical hypothyroidism (TSH ≥ 4.0 mIU/L), known hypothyroidism or hyperthyroidism (unless the condition has been stabilized with medication for at least 90 days prior to entry into Phase 1 or Phase 2).
* Subjects who have a medical history of uncontrolled diabetes, labile or unstable diabetes (brittle diabetes), newly diagnosed diabetes, or clinically significant abnormal blood glucose levels.

Primary outcomes:
measure: Overall Relapse Rate (in Percent) From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
Secondary outcomes:
measure: Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Percentage of Responders in Each Treatment Group.
timeFrame: Baseline to Week 52/End of Phase 3 visit
measure: Percentage of Participants Who Had Achieved Remission.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Percentage of Participants Who Discontinued Due to All Reasons Other Than Sponsor Discontinued Study.
timeFrame: Baseline to Week 52/End of Phase 3 visit
Other outcomes:
measure: Mean Change From Baseline to Endpoint in PANSS Total Score.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Mean Change From Baseline to Endpoint in CGI-S Score.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Mean CGI-I Score at Endpoint.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Mean Change From Baseline to Endpoint in PANSS Positive Subscale.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Mean Change From Baseline to Endpoint in PANSS Negative Subscale.
timeFrame: Baseline to Week 52/End of Phase 3 visit.
measure: Mean Change From Baseline to Endpoint in Children's Global Assessment Scale (CGAS).
timeFrame: Baseline to Week 52/End of Phase 3 visit.
Locations:
city: Downy
country: United States
facility: Study Site
state: California
city: Glendale
country: United States
facility: Study Site
state: California
city: Miami Springs
country: United States
facility: Study Site
state: Florida
city: Miami
country: United States
facility: Study Site
state: Florida
city: Atlanta
country: United States
facility: Study Site
state: Georgia
city: Bloomfield Hills
country: United States
facility: Study Site
state: Michigan
city: Chapel Hill
country: United States
facility: Study Site
state: North Carolina
city: Bothell
country: United States
facility: Study Site
state: Washington
city: Vijayawada
country: India
facility: Study Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Study Site
state: Andhra Pradesh
city: Raipur
country: India
facility: Study Site
state: Chhattisgarh
city: Maninagar, Ahmedabad
country: India
facility: Study Site
state: Gujarat
city: Aurangabad
country: India
facility: Study Site
state: Maharashtra
city: Wardha
country: India
facility: Study Site
state: Maharastra
city: Chennai
country: India
facility: Study Site
state: Tamil Nadu
city: Madurai
country: India
facility: Study Site
state: Tamil Nadu
city: Lucknow
country: India
facility: Study Site
state: Uttar Pradesh
city: Varanasi
country: India
facility: Study Site
state: Uttar Pradesh
city: Guntur
country: India
facility: Study Site
city: Ipoh
country: Malaysia
facility: Study Site
state: Perak
city: Batu Caves
country: Malaysia
facility: Study Site
state: Selangor darul Ehsan
city: Kuala Lumpur
country: Malaysia
facility: Study Site
state: Wilayah Persekutuan
city: Johor
country: Malaysia
facility: Study Site
city: Dasmarinas City
country: Philippines
facility: Study Site
state: Cavite
city: Bajada
country: Philippines
facility: Study Site
state: Davao City
city: Manila City
country: Philippines
facility: Study Site
state: Metro Manila
city: Iloilo City
country: Philippines
facility: Study Site
city: Mandaluyong City
country: Philippines
facility: Study Site
city: Cluj-Napoca
country: Romania
facility: Study Site
state: Cluj
city: Craiova
country: Romania
facility: Study Site
state: Dolj
city: Timisoara
country: Romania
facility: Study Site
state: Timis
city: Bucharest
country: Romania
facility: Study Site
city: Iasi
country: Romania
facility: Study Site
city: Arkhangelsk
country: Russian Federation
facility: Study Site
city: Ekaterinburg
country: Russian Federation
facility: Study Site
city: Kazan
country: Russian Federation
facility: Study Site
city: Lipetsk
country: Russian Federation
facility: Study Site
city: Moscow
country: Russian Federation
facility: Study Site
city: Moscow
country: Russian Federation
facility: Study Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Study Site
city: Novosibirsk
country: Russian Federation
facility: Study Site
city: Orenburg
country: Russian Federation
facility: Study Site
city: Petrozavodsk
country: Russian Federation
facility: Study Site
city: Saratov
country: Russian Federation
facility: Study Site
city: St. Petersburg
country: Russian Federation
facility: Study Site
city: St. Petersburg
country: Russian Federation
facility: Study Site
city: Tomsk
country: Russian Federation
facility: Study Site
city: Tonnelnyi Township
country: Russian Federation
facility: Study Site
city: Yaroslavl
country: Russian Federation
facility: Study Site
city: Kaohsiung County
country: Taiwan
facility: Study Site
city: Taipei City
country: Taiwan
facility: Study Site
city: Taoyuan County
country: Taiwan
facility: Study Site
Study officials:
affiliation: Otsuka Pharmaceutical Development and Commercialization, Inc.
name: Eva Kohegyi, MD
role: STUDY_DIRECTOR
References:
citation: Correll CU, Kohegyi E, Zhao C, Baker RA, McQuade R, Salzman PM, Sanchez R, Nyilas M, Carson W. Oral Aripiprazole as Maintenance Treatment in Adolescent Schizophrenia: Results From a 52-Week, Randomized, Placebo-Controlled Withdrawal Study. J Am Acad Child Adolesc Psychiatry. 2017 Sep;56(9):784-792. doi: 10.1016/j.jaac.2017.06.013. Epub 2017 Jul 8.