Efficacy & Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia

Schizophrenia Clinical Trial

— ATTAIN 266  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01149655
• Other study ID #: 31-09-266
• Status: Completed
• Phase: Phase 3
• First received: June 22, 2010
• Last updated: April 1, 2015
• Start date: July 2011
• Est. completion date: December 2013

Study information

• Verified date: April 2015
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRussia: Ministry of Health of the Russian FederationRomania: National Agency for Medicines and Medical DevicesIndia: Drugs Controller General of IndiaTaiwan : Food and Drug AdministrationPhilippines: Bureau of Food and DrugsMalaysia: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: December 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

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

Locations

Country	Name	City	State
India	Study Site	Aurangabad	Maharashtra
India	Study Site	Chennai	Tamil Nadu
India	Study Site	Guntur
India	Study Site	Lucknow	Uttar Pradesh
India	Study Site	Madurai	Tamil Nadu
India	Study Site	Maninagar, Ahmedabad	Gujarat
India	Study Site	Raipur	Chhattisgarh
India	Study Site	Varanasi	Uttar Pradesh
India	Study Site	Vijayawada	Andhra Pradesh
India	Study Site	Visakhapatnam	Andhra Pradesh
India	Study Site	Wardha	Maharastra
Malaysia	Study Site	Batu Caves	Selangor darul Ehsan
Malaysia	Study Site	Ipoh	Perak
Malaysia	Study Site	Johor
Malaysia	Study Site	Kuala Lumpur	Wilayah Persekutuan
Philippines	Study Site	Bajada	Davao City
Philippines	Study Site	Dasmarinas City	Cavite
Philippines	Study Site	Iloilo City
Philippines	Study Site	Mandaluyong City
Philippines	Study Site	Manila City	Metro Manila
Romania	Study Site	Bucharest
Romania	Study Site	Cluj-Napoca	Cluj
Romania	Study Site	Craiova	Dolj
Romania	Study Site	Iasi
Romania	Study Site	Timisoara	Timis
Russian Federation	Study Site	Arkhangelsk
Russian Federation	Study Site	Ekaterinburg
Russian Federation	Study Site	Kazan
Russian Federation	Study Site	Lipetsk
Russian Federation	Study Site	Moscow
Russian Federation	Study Site	Moscow
Russian Federation	Study Site	Nizhniy Novgorod
Russian Federation	Study Site	Novosibirsk
Russian Federation	Study Site	Orenburg
Russian Federation	Study Site	Petrozavodsk
Russian Federation	Study Site	Saratov
Russian Federation	Study Site	St. Petersburg
Russian Federation	Study Site	St. Petersburg
Russian Federation	Study Site	Tomsk
Russian Federation	Study Site	Tonnelnyi Township
Russian Federation	Study Site	Yaroslavl
Taiwan	Study Site	Kaohsiung County
Taiwan	Study Site	Taipei City
Taiwan	Study Site	Taoyuan County
United States	Study Site	Atlanta	Georgia
United States	Study Site	Bloomfield Hills	Michigan
United States	Study Site	Bothell	Washington
United States	Study Site	Chapel Hill	North Carolina
United States	Study Site	Downy	California
United States	Study Site	Glendale	California
United States	Study Site	Miami	Florida
United States	Study Site	Miami Springs	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  India,  Malaysia,  Philippines,  Romania,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean Change From Baseline to Endpoint in PANSS Total Score.	The PANSS consisted of 3 subscales with a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicates (absence of symptoms) and a score of 7 indicates (extremely severe symptoms). The symptom constructs for each subscale were positive subscale, negative subscale and general psychopathology subscale. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).	Baseline to Week 52/End of Phase 3 visit.	No
Other	Mean Change From Baseline to Endpoint in CGI-S Score.	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-s, the Investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0= not assessed; 1= normal, not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.	Baseline to Week 52/End of Phase 3 visit.	No
Other	Mean CGI-I Score at Endpoint.	Baseline for the double-blind maintenance phase was defined as the last visit with available data in the stabilization phase, and the CGI-I scale was completed prior to or on the first dose date in the double-blind maintenance phase. 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.	Baseline to Week 52/End of Phase 3 visit.	No
Other	Mean Change From Baseline to Endpoint in PANSS Positive Subscale.	The PANSS consisted of 3 subscales were a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated (absence of symptoms) and a score of 7 indicated (extremely severe symptoms). The 7 positive symptom constructs were delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).	Baseline to Week 52/End of Phase 3 visit.	No
Other	Mean Change From Baseline to Endpoint in PANSS Negative Subscale.	The PANSS consisted of 3 subscales were a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated (absence of symptoms) and a score of 7 indicated (extremely severe symptoms). The 7 negative symptom constructs were blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).	Baseline to Week 52/End of Phase 3 visit.	No
Other	Mean Change From Baseline to Endpoint in Children's Global Assessment Scale (CGAS).	The CGAS was developed by Schaffer and colleagues to provide a global measure of severity of disturbance in children and adolescents. The CGAS is a rating scale for evaluating the overall functioning of a participant during a specified time period on a continuum from psychological or psychiatric sickness to health. The CGAS is a valid and reliable tool for rating a child's general level of functioning on a health-illness continuum. CGAS score (range 1-100) was a single item score for rating a child's general level of functioning on a health-illness continuum, with higher scores represented better functioning.	Baseline to Week 52/End of Phase 3 visit.	No
Primary	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.	No
Secondary	Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.	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. 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.	No
Secondary	Percentage of Responders in Each Treatment Group.	Percentage of responders in each treatment group (i.e, response defined as meeting stability criteria). Participants stabilized on aripiprazole (trial drug) within the approved dose range of 10 to 30 mg/day and are tolerable based on clinical judgment.	Baseline to Week 52/End of Phase 3 visit	No
Secondary	Percentage of Participants Who Had Achieved Remission.	Percentage of participants who had achieved remission, where remission was defined as a score of = 3 on each of the following specific PANSS items, maintained for a period of 6 months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/ posturing, blunted affect, social withdrawal, and lack of spontaneity.	Baseline to Week 52/End of Phase 3 visit.	No
Secondary	Percentage of Participants Who Discontinued Due to All Reasons Other Than Sponsor Discontinued Study.	Percentage of participants discontinued due to all reasons other than sponsor discontinued study were noted.	Baseline to Week 52/End of Phase 3 visit	No