Efficacy & Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia

NCT01149655 | Completed Phase 3 Results DMC

• 1 other identifier: 31-09-266
• Study Type: interventional
• Target: 252
• Locations: 7 countries
• Sites: 52

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.

Conditions

Schizophrenia

Keywords

Adolescent; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Overall Relapse Rate (in Percent) From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse.

  The primary efficacy variable was overall relapse rate from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \> 4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content). OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.

  Baseline to Week 52/End of Phase 3 visit.

Secondary Outcomes (4)

• Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.

  Baseline to Week 52/End of Phase 3 visit.

• Percentage of Responders in Each Treatment Group.

  Baseline to Week 52/End of Phase 3 visit

• Percentage of Participants Who Had Achieved Remission.

  Baseline to Week 52/End of Phase 3 visit.

• Percentage of Participants Who Discontinued Due to All Reasons Other Than Sponsor Discontinued Study.

  Baseline to Week 52/End of Phase 3 visit

Other Outcomes (6)

• Mean Change From Baseline to Endpoint in PANSS Total Score.

  Baseline to Week 52/End of Phase 3 visit.

• Mean Change From Baseline to Endpoint in CGI-S Score.

  Baseline to Week 52/End of Phase 3 visit.

• Mean CGI-I Score at Endpoint.

  Baseline to Week 52/End of Phase 3 visit.

Study Arms (3)

Phase 1

EXPERIMENTAL

Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)

Drug: Aripiprazole

Phase 2

EXPERIMENTAL

Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)

Drug: Aripiprazole

Phase 3

PLACEBO COMPARATOR

Aripiprazole (10-mg, 15-mg, 20-mg, 25-mg or 30-mg) or placebo

Drug: Aripiprazole

Interventions

Aripiprazole DRUG

Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)

Phase 1; Phase 2

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (52)

Study Site

Downy, California, 90241, United States

Location

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Glendale, California, 91204, United States

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Miami, Florida, 33155, United States

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Miami Springs, Florida, 33166, United States

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Atlanta, Georgia, 30308, United States

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Bloomfield Hills, Michigan, 48302, United States

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Chapel Hill, North Carolina, 27517, United States

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Bothell, Washington, 98011, United States

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Vijayawada, Andhra Pradesh, 520002, India

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Visakhapatnam, Andhra Pradesh, 530017, India

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Raipur, Chhattisgarh, 492001, India

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Maninagar, Ahmedabad, Gujarat, 380008, India

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Aurangabad, Maharashtra, 431005, India

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Wardha, Maharashtra, 442004, India

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Chennai, Tamil Nadu, 600003, India

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Madurai, Tamil Nadu, 625020, India

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Lucknow, Uttar Pradesh, 226003, India

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Varanasi, Uttar Pradesh, 221005, India

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Guntur, 522001, India

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Kuala Lumpur, Kuala Lumpur, 50603, Malaysia

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Ipoh, Perak, 30450, Malaysia

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Batu Caves, Selangor, 68100, Malaysia

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Johor Bahru, 81200, Malaysia

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Dasmariñas, Cavite, 4114, Philippines

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Bajada, Davao City, 8000, Philippines

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Manila, National Capital Region, 1000, Philippines

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Iloilo City, 5000, Philippines

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Mandaluyong, 1553, Philippines

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Cluj-Napoca, Cluj, 400084, Romania

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Craiova, Dolj, 200620, Romania

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Timișoara, Timiș County, 300239, Romania

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Bucharest, 041914, Romania

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Iași, 700282, Romania

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Arkhangelsk, 163530, Russia

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Kazan', 420061, Russia

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Lipetsk, 399313, Russia

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Moscow, 124617, Russia

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Moscow, 127083, Russia

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Nizhny Novgorod, 603155, Russia

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Novosibirsk, 630091, Russia

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Orenburg, 460000, Russia

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Petrozavodsk, 185001, Russia

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Saint Petersburg, 190005, Russia

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Saint Petersburg, 197376, Russia

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Saratov, 410028, Russia

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Tomsk, 634014, Russia

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Tonnelnyi Township, 357034, Russia

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Yaroslavl, 150003, Russia

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Yekaterinburg, 620030, Russia

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Kaohsiung County, 833, Taiwan

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Taipei, 110, Taiwan

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Taoyuan, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 28838583 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800 562-3974

Study Officials

• Eva Kohegyi, MD

  Otsuka Pharmaceutical Development and Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: June 23, 2010
• Study Start: July 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 2, 2015
• Results First Posted: April 2, 2015

Record last verified: 2015-04

Locations

US (8); PH (5); RO (5); RU (16); MY (4); TW (3); IN (11)