Clinical Trial Results:
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
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Summary
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EudraCT number |
2010-018911-13 |
Trial protocol |
PL BG HU |
Global end of trial date |
07 Sep 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
09 Apr 2016
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First version publication date |
12 Aug 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
31-09-267
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01122927 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Otsuka Pharmaceutical Development & Commercialization, Inc.
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Sponsor organisation address |
2440 Research Boulevard, Rockville, Maryland, United States, 20850
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Public contact |
Dorota Plewicka , Covance CAPS Ltd, 47 578213 25, dorota.plewicka@covance.com
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Scientific contact |
Dorota Plewicka , Covance CAPS Ltd, 47 578213 25, dorota.plewicka@covance.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000235-PIP02-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Jan 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Sep 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Sep 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The objective of this trial was to further characterize the long-term safety and tolerability of aripiprazole in adolescent subjects with schizophrenia and child and adolescent subjects with bipolar I disorder, manic or mixed episode, with or without psychotic features.
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Protection of trial subjects |
The trial was conducted in compliance with the protocol, International Conference on Harmonisation Good Clinical Practice (ICH-GCP), and applicable local laws and regulatory requirements. Written informed consent was obtained from each participant's legally acceptable representative as applicable for local laws, and informed assent was obtained from all participants, as applicable for local laws. Informed consent/assent, as applicable for local laws, was obtained and documented prior to initiation of any procedures that were performed solely for the purpose of determining eligibility for this trial, including withdrawal from current medications. All participants received copies of their signed and dated Informed consent forms (ICFs).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Aug 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 105
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Country: Number of subjects enrolled |
Bulgaria: 70
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Country: Number of subjects enrolled |
Croatia: 7
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Country: Number of subjects enrolled |
Hungary: 12
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Country: Number of subjects enrolled |
India: 93
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Country: Number of subjects enrolled |
Philippines: 12
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Country: Number of subjects enrolled |
Poland: 24
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Country: Number of subjects enrolled |
Romania: 17
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Country: Number of subjects enrolled |
Russian Federation: 73
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Country: Number of subjects enrolled |
Serbia: 12
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Country: Number of subjects enrolled |
Taiwan: 1
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Country: Number of subjects enrolled |
Ukraine: 98
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Worldwide total number of subjects |
524
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EEA total number of subjects |
130
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
18
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Adolescents (12-17 years) |
493
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Adults (18-64 years) |
13
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This trial was conducted in 524 participants at 118 trial sites in 13 countries. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
524 participants entered this trial (297 participants in the conversion phase and 510 participants in the open-label treatment phase). In the latter, 362 were de novo participants (280 participants entered into the conversion phase) and 148 rolled over from Trial 2010-020987-39. 416 participants had schizophrenia and 94 had bipolar disorder. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Blinding implementation details |
Not applicable for this open-label trial.
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Arms
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Arm title
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All Participants | ||||||||||||||||||||||||
Arm description |
Data for all the participants were analyzed. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Aripiprazole
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Investigational medicinal product code |
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Other name |
Abilify, OPC-14597
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered oral aripiprazole titrated from 10 to 30 milligram per day (mg/day), with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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Baseline characteristics reporting groups
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Reporting group title |
All Participants
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Reporting group description |
Data for all the participants were analyzed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All Participants
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Reporting group description |
Data for all the participants were analyzed. | ||
Subject analysis set title |
Open-label Treatment Phase
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants were administered oral aripiprazole titrated from 10 to 30 milligram per day (mg/day), with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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Subject analysis set title |
Tanner score at Baseline of 1
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who entered this phase had received oral aripiprazole titrated from 10 to 30 mg/day, with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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Subject analysis set title |
Tanner score at Baseline of 2
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who entered this phase had received oral aripiprazole titrated from 10 to 30 mg/day, with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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Subject analysis set title |
Tanner score at Baseline of 3
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who entered this phase had received oral aripiprazole titrated from 10 to 30 mg/day, with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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Subject analysis set title |
Tanner score of Baseline of 4
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who entered this phase had received oral aripiprazole at a target dose of 10 to 30 mg/day, with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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Subject analysis set title |
Tanner score of Baseline of 5
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who entered this phase had received oral aripiprazole titrated from 10 to 30 mg/day, with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations.
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End point title |
Number of participants with adverse events (AEs) [1] | ||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant or participant enrolled in a clinical trial and which did not necessarily have a causal relationship with the study medication. A treatment emergent adverse event (TEAE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study medication, whether or not considered to have a causal relationship with the study medication. A serious-AE or reaction was any untoward occurrence that, at any dose, was fatal, life-threatening, required inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was any other medically significant event that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.
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End point type |
Primary
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End point timeframe |
Adverse events were recorded from the time of the informed consent was signed until the follow-up visit 30 (± 3) days after the end of trial.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis provided for Number of participants with adverse events (AEs). |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Incidence of laboratory values of potential clinical relevance | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria. Abnormal laboratory values in participants were reported as SAE/AEs and are reported in the SAE/non-serious AE section of this report.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Incidence of physical examination findings of potential clinical relevance | ||||||
End point description |
The physical examination evaluation was one of the parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||
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End point title |
Incidence of vital signs of potential clinical relevance | ||||||||||||||||||||||||||||||||||
End point description |
Vital signs are taken at Baseline, Weeks 1, 2, 3, 4, 6, 8, and Months 3, 4, 6, 9, 12, 15, 18, 21, 24 of Phase 2 (Visits beyond Month 12 only for de novo subjects). Assessments included orthostatic (supine and standing) blood pressure (BP) measured as millimeter of mercury [mmhg]), heart rate and body temperature. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate (measured as beats per minutes [bpm]), systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria. Abnormal vital signs in participants were reported as SAE/AEs and are reported in the SAE/non-serious AE section of this report.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
Mean change from Baseline by Week in Abnormal Involuntary Movement Scale (AIMS) | ||||||||||||||||||||||||||||||||||||
End point description |
The AIMS Scale was an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10). The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Mean change from Baseline by Week in Simpson-Angus Scale (SAS) total score | ||||||||||||||||||||||||||||||||||||
End point description |
The SAS is a rating scale used to measure EPS. The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Mean change from Baseline by Week in Barnes Akathisia Rating Scale (BARS) score | ||||||||||||||||||||||||||||||||||||
End point description |
The BARS was an EPS rating scale. The BARS was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia).
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants with cognitive impairment for each New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) | ||||||||||||||||||||
End point description |
The NY-AACENT is not a validated scale. It was included in this trial because of concerns that regulatory authorities (the European Committee for Medicinal Products for Human Use [CHMP] and the Paediatric Sub-Committee of the European Medicinal Agency [PDCO]) had regarding drug induced cognitive impairment. No validated scale addressing these issues was available at the time of the trial. The NY-AACENT was used to detect changes in cognitive function subsequent to pharmacological or similar treatments for neurological or psychiatric problems. It was specifically designed to be used in paediatric populations (ages 12 to 17), but could have been utilized with other age groups, as appropriate.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Baseline and Post-Baseline Tanner Staging | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Tanner staging was completed together with the physical examination by the same trial-affiliated clinician in the most inconspicuous manner for the participant as possible. Tanner staging assessment consisted of 2 domains (pubic hair and breast development) for girls and 3 domains (pubic hair, penis development, and testes development) for boys. A participant who reached Stage 5 (both in pubic hair and genitalia) did not need to continue with Tanner Staging assessment and the Tanner Staging scales of this participant were imputed as 5 for all of the following scheduled time points up to and including the completion visit/early termination (ET) visit. The clinician arrived at a single score summarizing the domains (not individual domain scores) when evaluating the participant. The total shift data for last visit is presented below.
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End point type |
Secondary
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End point timeframe |
Baseline to Last Visit
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Mean change from Baseline for Columbia-Suicide Severity Rating Scale (C-SSRS) in Suicidal Ideation Intensity Total Score | ||||||||||||||||||||||||||||||||||||||||
End point description |
Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Suicidal ideation was defined as reporting any type of suicidal ideation. The suicidal ideation intensity total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) which leads to the range of the total score from 0 to 25. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of participants who discontinued due to all adverse events | ||||||||||||
End point description |
The time to discontinuations due to all causes other than sponsor terminating the trial was measured from the date of entering the open-label treatment phase to the date of ET for discontinued participants in the open-label treatment phase (ie, time to discontinuation = date of discontinuation [or date of completion for completed participants] − date of participant entering the open-label treatment phase + 1). If the participants completed the trial or were discontinued due to the sponsor terminating the trial, they were censored at the time of completion or trial termination, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in Positive and Negative Symptoms Score (PANSS) total score | ||||||||||||
End point description |
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in PANSS positive subscale score | ||||||||||||
End point description |
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in PANSS negative subscale score | ||||||||||||
End point description |
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in Clinical Global Impression-Severity (CGI-S) Score | ||||||||||||
End point description |
The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician 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 ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean in Clinical Global Impression-Improvement (CGI-I) score | ||||||||||||
End point description |
The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 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.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in Young Mania Rating Scale (YMRS) score | ||||||||||||
End point description |
The YMRS consists of 11 items assessing the core symptoms of mania and was used to assess participants with bipolar I disorder, manic and mixed episodes with or without psychotic features: elevated mood, increased motor activity - energy, sexual interest, sleep, irritability, speech (rate and amount), language - thought disorder, content, disruptive - aggressive behavior, appearance, and insight. Each item had 5 or 9 grades of severity, with lower scores indicating milder symptoms. The number of raters within each trial center was to be kept to a minimum. The YMRS Total Score (range 0 to 44) is the sum of the rating scores for 11 items for assessing the core symptoms of mania. A missing value for any YMRS assessment item(s) could have resulted in a missing YMRS Total Score. A higher YMRS Total Score represents greater severity. In this study, 94 participants had bipolar disorder, this explains the N=94 in the table below and these were de novo participants.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in Clinical Global Impression Scale - Bipolar (CGI-BP) version severity score | ||||||||||||
End point description |
The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rated the subject’s Severity of Illness (CGI-BP-Severity: mania, depression, and overall bipolar illness) and Change From Preceding Phase (CGI-BP-Improvement: mania, depression, and overall bipolar illness) based on a 7- or 8-point scale. Severity of Illness (CGI-BP-Severity) was rated at all visits. At each visit other than Day 0 (Baseline), the Change From Preceding Phase (CGI-BP-Improvement) was judged with respect to participant's condition at Baseline. The CGI-BP Severity Scores (range 1 to 7), as well as CGI-BP Improvement Scores (range 1 to 7) are single-item rating scores, with higher scores representing greater severity or less improvement. Data for 94 de novo participants were available with bipolar disorder.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in Clinical Global Impression Scale - Bipolar version improvement score | ||||||||||||
End point description |
The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rated the subject’s Severity of Illness (CGI-BP-Severity: mania, depression, and overall bipolar illness) and Change From Preceding Phase (CGI-BP-Improvement: mania, depression, and overall bipolar illness) based on a 7- or 8-point scale. Severity of Illness (CGI-BP-Severity) was rated at all visits. At each visit other than Day 0 (Baseline), the Change From Preceding Phase (CGI-BP-Improvement) was judged with respect to participant's condition at Baseline. The CGI-BP Severity Scores (range 1 to 7), as well as CGI-BP Improvement Scores (range 1 to 7) are single-item rating scores, with higher scores representing greater severity or less improvement. Only 40 participants had data at Baseline to explain the N=40 in the table below and these were de novo participants.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in General Behavior Inventory (GBI) Scale Total Score for Mania and Depression in both Parent/Guardian and Subject versions of the scale | ||||||||||||
End point description |
The GBI is a self-report inventory with 73 items focusing on mood-related behaviors, including depressive, hypomanic, and biphasic symptoms. For this trial, two 20-item subscales were utilized: one was completed by the parent/guardian or legal representative, as applicable for local laws, and the other was completed by the participant. Responses were given on a 4-point Likert scale, with 0 being never or hardly ever and 3 being very often or almost constantly. The GBI Total Score for mania (range 0 to 30) is the sum of scores for items 1 to 10 and the GBI Total Score for depression (range 0 to 30) is the sum of scores for items 11 to 20 in the GBI Parent/Guardian or Subject Version panel. Scores from the Parent/Guardian and participant Versions were summarized separately. A missing value for any GBI assessment items could have resulted in a missing GBI Total Score. High scores represent greater psychopathology. Data was only available for 80 de novo participants with bipolar disorder.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in the Attention Deficit Hyperactive Disorders Rating (ADHD-RS-IV) scale score | ||||||||||||
End point description |
The ADHD-RS-IV is a reliable and easy-to-administer instrument both for diagnosing ADHD in children and adolescents and for assessing treatment response. Containing 18 items, the scale was linked directly to DSM-IV-TR diagnostic criteria for ADHD. There were 3 versions of the scale: a parent questionnaire on home behaviors (English), a parent questionnaire on home behaviors (Spanish), and a teacher questionnaire on classroom behaviors. For this trial, the parent questionnaire on home behaviors (English) was utilized. The ADHD-RS-IV Total Score (range 0 to 54) is the sum of rating scores for 18 items, with higher scores representing greater severity. A missing value for any ADHD-RS-IV assessment items could have resulted in a missing ADHD-RS-IV Total Score. Data were only available for 82 participants with bipolar disorder and these were de novo participants.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in Children's Global Assessment Scale (CGAS) in Bipolar (de novo participants) | ||||||||||||
End point description |
The CGAS is a 100-point rating scale measuring psychological, social, and school functioning for children aged 6 to 17. It was adapted from the Adults Global Assessment Scale. The Global Assessment Scale was 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. The CGAS was developed by Schaffer and colleagues to provide a global measure of severity of disturbance in children and adolescents. The CGAS Score (range 1 to 100) is a single-item score for rating a child’s general level of functioning on a health-illness continuum, with higher scores representing better functioning.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Incidence of suicidality, suicidal behaviour and suicidal ideation | ||||||||||||||||||||||||
End point description |
Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Suicidal ideation was defined as reporting any type of suicidal ideation. The below reported N value is the number of participants with specified suicidal ideation/behavior at the given time point.
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End point type |
Secondary
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End point timeframe |
Baseline to Month 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were reported from the signing of the informed consent until the follow-up visit 30 (± 3) days after the end of trial.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Conversion Phase
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Reporting group description |
Participants who entered this phase were converted from his or her antipsychotic to the minimum target dose of 10 mg/day aripiprazole monotherapy and continue to increase the dose up to a maximum of 30 mg/day, or for tolerability reasons, to reduce the aripiprazole dose to no less than 5 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Open-label Treatment Phase
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Reporting group description |
Participants who entered this phase had received oral aripiprazole at a target dose of 10 to 30 mg/day, with a minimum dose of 5 mg/day, based on individual participant's response and tolerability considerations. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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13 Aug 2010 |
In protocol amendment 1, provided instructions for titrating de novo subjects who were treated with a marketed long-acting intramuscular depot antipsychotic for <1 cycle plus 14 days or <60 days prior to screening. Updated the number of participants expected to rollover from Trial 31-09-266 from 180 to 63. Added child and adolescent participants with bipolar I disorder, manic or mixed episode with or without psychotic features to the trial population. Added the restrictions on treatment with benzodiazepines or propranolol within 8 hours or treatment with anticholinergic agents within 12 hours prior to all trial assessments during any phase of the trial. Added sections on YMRS, CGI-BP, GBI, ADHD-RS-IV, and K-SADS-PL to instruct investigators on these assessments. Instructed investigators to identify and to report participants (within 24 hours) who met the criteria for potential drug induced liver damage (Hy’s Law). Provided additional instructions on how long birth control was to be used for female participants of childbearing potential and female partners of male participants and included birth control depot injections as an acceptable form of birth control. Provided time windows for prohibited concomitant antidepressants prior to entry into the conversion phase or the open-label treatment phase. Clarified that all participants require a K-SADS-PL assessment prior to entering the conversion phase or the open-label treatment phase of Trial 31-09-267. |
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14 Dec 2010 |
In protocol amendment 2, Changed the trial designation from Phase 4 to Phase 3. Added 3 safety rating scales to the protocol: the Clinician Pediatric Adverse Event Rating Scale (PAERS), Sexual Adverse Event Scale (SAES), and NY-AACENT scales. Excluded participants who used clozapine at any time. Excluded participants with a positive cannabis test at screening. Excluded participants who used an intramuscular depot long-acting antipsychotic within 6 months of beginning trial treatment. Excluded participants with evidence of subclinical hypothyroidism. Updated the number of participants required to be screened. Changed the wording for parent or guardian to parent/guardian or legal representative, as applicable for local laws. |
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28 Mar 2011 |
In protocol amendment 3, Changed the exclusionary QTc value from ≥ 420 to ≥450 msec. Clarified that a clinically significant fasting blood glucose level, requiring trial exclusion was ≥125 mg/dL. Added statement that participants who previously screen failed due to QTc ≥ 420 msec were allowed to be rescreened. Changed second hypothyroidism to hyperthyroidism in the inclusion criteria 12. Added procedure at ET or completion visits that participants were discontinued in the Interactive voice response system/Interactive web response system (IVRS/IWRS). Added documentation of birth control status at the follow-up visit. Changed Phase 3 to Phase 2 in the following sentence: “The incidence of the symptom items recorded in the three adverse event scales at each visit will be summarized for the Phase 2 Safety Sample by disease under study and by treatment group (aripiprazole and placebo) for the Phase 3 Safety Sample.” Removed the planned summary of Tanner Staging scores using their cross frequencies at baseline and postbaseline by treatment group. Added protocol dates to the footer and added the Investigational New Drug (IND) number to the title page and protocol synopsis. Removed all references to the SAES and PAERS from the protocol. Updated the ECG language. Clarified which medications are prohibited. Changed the number of trial sites from up to 75 to approximately 75 sites. Clarified the titration requirements for rollover subjects from Trial 31-09-266. Clarified the use of titration cards for participants on < 5 and 5 mg/day of branded aripiprazole. Clarified that oral aripiprazole was not to be dispensed at Week 6/end of the conversion phase. Clarified that a rollover participants CGI-I baseline score was based on the participants status at the last visit of Trial 31-09-266. |
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21 Mar 2012 |
In protocol amendment 4, Increased the sample size to meet the requirement set forth as a key binding element of the European Medicines Agency (EMA) P/99/2011 Aripiprazole Paediatric Investigational Plan to provide 2 years of safety data for at least 100 subjects, including Tanner Staging and cognitive AEs. Adjusted the assumptions for screening failure rate and the discontinuation rate in the conversion phase based on actual trial data. Updated the amendment with new safety information and aripiprazole Investigator Brochure, Version No. 15. Deleted the version of MedDRA that was to be used to code AEs. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
