Clinical trial NCT01122927: Safety and Tolerability of Aripiprazole in Adolescents With Schizophrenia or Children and Adolescents With Bipolar I Disorder, Manic or Mixed Episode With or Without Psychotic Features.
Official title: A Long-term, Multicenter, Open-Label Study to Evaluate the Safety and Tolerability of Flexible-Dose Oral Aripiprazole (OPC-14597) as Maintenance Treatment in Adolescent Patients With Schizophrenia or Child and Adolescent Patients With Bipolar I Disorder, Manic or Mixed Episode With or Without Psychotic Features
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Adolescent Schizophrenia
Child or Adolescent Bipolar I Disorder, Manic or Mixed Episode With or Without Psychotic Features
Keywords: schizophrenia
adolescent
bipolar
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2010-05-13
Enrollment: 524
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label study consisting of a screening period, a conversion/titration phase (Phase 1), an open-label treatment phase (Phase 2), and a follow-up period.

The study will enroll new subjects (hereafter referred as "de novo" subjects) with schizophrenia, or bipolar I disorder, manic or mixed episode with or without psychotic features, and rollover subjects with schizophrenia from 31-09-266 (hereafter referred to as "Study 266"). All de novo subjects must enter the screening period of the study. Subjects who are screened and are not required to go through Phase 1 will complete a Phase 2 baseline visit prior to their participation in Phase 2.

Study Design: Treatment, Single Group Assignment, Open Label, Active Control, Safety/Efficacy Study


Eligibility criteria: Inclusion Criteria:

* Subjects 13-17 years old (Schizophrenia); Subjects 10-17 years old (Bipolar manic or mixed episode)\* \[\*Bulgaria will enroll Schizophrenia subjects only.\]
* Subjects with a current diagnosis of schizophrenia, and a history of the illness (diagnosis or symptoms) for at least 6 months prior to screening (as per subject, family, or healthcare provider, or by previous medical records).
* Subjects with a current diagnosis of bipolar I disorder, manic or mixed episode with or without psychotic features (diagnosis or symptoms) experiencing symptoms for at least 1 week prior to screening. \* \[\*These subjects will not be eligible to enroll in Bulgaria\]
* 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 antipsychotics other than clozapine, and are not resistant to treatment with other antipsychotics.
* Inpatient or outpatient status, with the exception of acute hospitalization due to psychiatric reasons at the time of screening or before Phase 2.

Exclusion Criteria:

* All subjects: diagnosis of schizoaffective disorder, autism, pervasive developmental disorder (PDD), OCD, or PTSD.
* Subjects with schizophrenia: a current major depressive episode.
* Subjects with bipolar manic or mixed episode: presenting with a clinical picture and/or history that is consistent with a diagnosis of bipolar II disorder or bipolar disorder not otherwise specified.
* 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 any neurological disorder, with the exception of Tourette's syndrome.
* Subjects experiencing major depressive episode at the time of screening other than subjects diagnosed with bipolar I disorder mixed episode.
* Subjects who are currently receiving clozapine or have received clozapine at any time in the past are ineligible for entry into the study.
* 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 medications 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 (defined as fasting blood glucose ≥ 125 mg/dL).

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Adverse events were recorded from the time of the informed consent was signed throughout the 24 month treatment period until the follow-up visit 30 (± 3) days after the end of trial.
Secondary outcomes:
measure: Incidence of Laboratory Values of Potential Clinical Relevance
timeFrame: Baseline to Month 24
measure: Incidence of Physical Examination Findings of Potential Clinical Relevance
timeFrame: Baseline to Month 24
measure: Incidence of Vital Signs of Potential Clinical Relevance
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline by Week in Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline by Week in Simpson-Angus Scale (SAS) Total Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline by Week in Barnes Akathisia Rating Scale (BARS) Score
timeFrame: Baseline to Month 24
measure: Number of Participants With Cognitive Impairment for Each New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT)
timeFrame: Baseline to Month 24
measure: Baseline and Post-Baseline Tanner Staging
timeFrame: Baseline to Last Visit
measure: Mean Change From Baseline for Columbia-Suicide Severity Rating Scale (C-SSRS) in Suicidal Ideation Intensity Total Score
timeFrame: Baseline to Month 24
measure: Incidence of Suicidality, Suicidal Behavior and Suicidal Ideation
timeFrame: Baseline to Month 24
measure: Percentage of Participants Who Discontinued Due to All Adverse Events
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in Positive and Negative Symptoms Score (PANSS) Total Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in PANSS Positive Subscale Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in PANSS Negative Subscale Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline to Month 24
measure: Mean Change in Clinical Global Impression-Improvement (CGI-I) Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in Young Mania Rating Scale (YMRS) Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in Clinical Global Impression Scale - Bipolar (CGI-BP) Version Severity Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in Clinical Global Impression Scale - Bipolar Version Improvement Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in General Behavior Inventory (GBI) Scale Total Score for Mania and Depression in Both Parent/Guardian and Subject Version of the Scale
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in the Attention Deficit Hyperactive Disorders Rating (ADHD-RS-IV) Scale Score
timeFrame: Baseline to Month 24
measure: Mean Change From Baseline in Children's Global Assessment Scale (CGAS) in Bipolar (de Novo Participants)
timeFrame: Baseline to Month 24
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Study Site
state: Alabama
city: Downey
country: United States
facility: Study Site
state: California
city: Miami
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: Smyrna
country: United States
facility: Study Site
state: Georgia
city: Oak Brook
country: United States
facility: Study Site
state: Illinois
city: Wichita
country: United States
facility: Study Site
state: Kansas
city: Minneapolis
country: United States
facility: Study Site
state: Minnesota
city: Buffalo
country: United States
facility: Study Site
state: New York
city: Stony Brook
country: United States
facility: Study Site
state: New York
city: Chapel Hill
country: United States
facility: Study Site
state: North Carolina
city: Cincinnati
country: United States
facility: Study Site
state: Ohio
city: Cleveland
country: United States
facility: Study Site
state: Ohio
city: Oklahoma City
country: United States
facility: Study Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Study Site
state: Pennsylvania
city: Houston
country: United States
facility: Study Site
state: Texas
city: San Antonio
country: United States
facility: Study Site
state: Texas
city: The Woodlands
country: United States
facility: Study Site
state: Texas
city: Richmond
country: United States
facility: Study Site
state: Virginia
city: Bellevue
country: United States
facility: Study Site
state: Washington
city: Bothell
country: United States
facility: Study Site
state: Washington
city: Milwaukee
country: United States
facility: Study Site
state: Wisconsin
city: Bourgas
country: Bulgaria
facility: Study Site
city: Pazardjik
country: Bulgaria
facility: Study Site
city: Plovdiv
country: Bulgaria
facility: Study Site
city: Rousse
country: Bulgaria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site 2
city: Targovishte
country: Bulgaria
facility: Study Site
city: Varna
country: Bulgaria
facility: Study Site 1
city: Varna
country: Bulgaria
facility: Study Site 2
city: Rijeka
country: Croatia
facility: Study Site
city: Zagreb
country: Croatia
facility: Study Site 1
city: Zagreb
country: Croatia
facility: Study Site 2
city: Budapest
country: Hungary
facility: Study Site
city: Budapest
country: Hungary
facility: Study Site
city: Gyula
country: Hungary
facility: Study Site
city: Szeged
country: Hungary
facility: Study Site
city: Vijayawada
country: India
facility: Study Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Study Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Study Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Study Site 1
state: Gujarat
city: Ahmedabad
country: India
facility: Study Site 2
state: Gujarat
city: Ahmedabad
country: India
facility: Study Site
state: Gujarat
city: Maninagar, Ahmedabad
country: India
facility: Study Site
state: Gujarat
city: Mangalore
country: India
facility: Study Site
state: Karnataka
city: Calicut
country: India
facility: Study Site
state: Kerala
city: Nasik
country: India
facility: Study Site
state: Maharashtra
city: Ludhiana
country: India
facility: Study Site
state: Punjab
city: Jaipur
country: India
facility: Study Site
state: Rajasthan
city: Chennai
country: India
facility: Study Site
state: Tamil Nadu
city: Maduri
country: India
facility: Study Site
state: Tamil Nadu
city: Kanpur
country: India
facility: Study Site
state: Uttar Pradesh
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: Kuala Lumpur
country: Malaysia
facility: Study Site
state: Wilayah Persekutuan
city: Dasmarinas City
country: Philippines
facility: Study Site
state: Cavite
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: Białystok
country: Poland
facility: Study Site
city: Gdansk Wrzeszcz
country: Poland
facility: Study Site
city: Toruń
country: Poland
facility: Study Site
city: Wrocław
country: Poland
facility: Study Site
city: Wrocław
country: Poland
facility: Study Site
city: Cluj-Napoca
country: Romania
facility: Study Site
state: Cluj
city: Timisoara
country: Romania
facility: Study Site
state: Timis
city: Bucharest
country: Romania
facility: Study Site
city: Craiova, Dolj
country: Romania
facility: Study Site
city: Iasi
country: Romania
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 region
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: Belgrade
country: Serbia
facility: Study Site 1
city: Belgrade
country: Serbia
facility: Study Site 2
city: Novi Sad
country: Serbia
facility: Study Site
city: Taipei City
country: Taiwan
facility: Study Site
city: Dnepropetrovsk
country: Ukraine
facility: Study Site
city: Donetsk
country: Ukraine
facility: Study Site
city: Kharkiv
country: Ukraine
facility: Study Site 1
city: Kharkiv
country: Ukraine
facility: Study Site 2
city: Kherson
country: Ukraine
facility: Study Site
city: Lugansk
country: Ukraine
facility: Study Site
city: Lviv
country: Ukraine
facility: Study Site
city: Odessa
country: Ukraine
facility: Study Site
city: Simferopol Crimea
country: Ukraine
facility: Study Site
city: Temopil
country: Ukraine
facility: Study Site
city: Vinnytsya
country: Ukraine
facility: Study Site
Study officials:
affiliation: Otsuka Pharmaceutical Development and Commercialization, Inc.
name: Eva Kohegyi, MD
role: STUDY_DIRECTOR
References: