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Safety And Tolerability Of Ziprasidone In Adolescents With Schizophrenia

Phase 3
Terminated
Conditions
Schizophrenia
Interventions
Registration Number
NCT00265382
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Brief Summary

The purpose of this study is to assess the safety and tolerability of ziprasidone during long-term open-label administration in adolescents (ages 13-17) with schizophrenia.

Detailed Description

On March 24, 2009, Pfizer Inc. stopped late stage Geodon pediatric clinical trials in schizophrenia (A1281134 - placebo controlled; A1281135 - open label). As recommended by the DSMB, these studies were stopped due to lack of efficacy. No safety concerns were identified.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
221
Inclusion Criteria
  • Participation in double-blind treatment study A1281134, meeting specific criteria of duration and safety
Exclusion Criteria
  • Imminent risk of suicide or homicide, as judged by the site investigator
  • Serious adverse event related to study medication in study A1281134
  • Significant prolongation of QT interval in study A1281134

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
OpenZiprasidone oral capsules-
Primary Outcome Measures
NameTimeMethod
Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)26 weeks

All observed or volunteered treatment-emergent AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.

Secondary Outcome Measures
NameTimeMethod
Number of Subjects With Change From Baseline to Each Pubertal Stage of Development as Assessed by the Tanner Adolescent Pubertal Self AssessmentBaseline, Week 26, Early Termination (ET)

Tanner Adolescent Pubertal Staging Questionnaire: used to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; males pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size).

Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total ScoreBaseline, Weeks 2, 6, 18, 26, ET

CPBAQ: 19-item parent or legal guardian completed questionnaire to rate the child's verbal (such as yelling or cursing) and physical aggression (such a fighting with peers or being cruel to an animal) during the past week. Behavior was rated on a 4-point scale; range 0 (behavior did not occur or was not a problem) to 3 (behavior occurred a lot or was severe problem). Total score range 0 to 57; higher scores indicate a greater frequency and severity of aggression.

Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total ScoreBaseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET

CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment). Total score calculated as sum of the 17 items (range 1 to 119); higher score indicates greater impairment.

Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): SubscalesBaseline, Weeks 6 and 26, ET

Computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, sustained attention. Computerized 7- point sedation item (0 \[not sleepy\] to 10 \[very sleepy\]) was completed prior to test battery. Neurocognitive index score was derived from subtest scores per an algorithm. Index score and subtest scores assessed the subject's changes in cognition. Scores were rated as above average (score \>109), average (90 to 109), below average (80 to 89), or well below average (70 to 79).

Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive IndexBaseline, Weeks 6 and 26, ET

Computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, sustained attention. Computerized 7- point sedation item (0 \[not sleepy\] to 10 \[very sleepy\]) was completed prior to test battery. Neurocognitive index score was derived from subtest scores per an algorithm. Index score and subtest scores assessed the subject's changes in cognition. Scores were rated as above average (score \>109), average (90 to 109), below average (80 to 89), or well below average (70 to 79).

Change From Baseline in Simpson-Angus Rating Scale (SARS)Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET

SARS: 10-item clinician rated instrument to assess parkinsonian symptoms (7 items) and related extrapyramidal side effects (3 items): gait, arm dropping, shoulder shaking, elbow rigidity, leg pendulousness, glabellar tap, tremor, and salivation. Head dropping (modified SARS item 7) substituted for head rotation. Anchored 5-point scale: range 0 (absence of condition, normal) to 4 (most extreme form of condition). Total score is sum of individual item scores (range 0 to 40); higher score indicates more affected.

Change From Baseline in Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment ItemBaseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET

BAS: clinician rated scale to assess akathisia to determine the degree of subjective restlessness and distress associated with restlessness. First 3 items (Objective, Subjective, and Distress related to restlessness) rated on a 4-point scale with range 0 (no symptoms) to 3 (increased severity of symptoms). Item 4 Global Clinical Assessment of Akathisia rated on a 6- point scale range 0 (no symptoms) to 5 (increased severity of symptoms); higher score indicates increased severity. All rating are anchored. Only the Global Clinical Assessment of Akathisia was to be analyzed.

Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Cluster ScoreBaseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET

AIMS: clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe) (total possible score 0 to 40; higher score indicates greater severity); items 11 to 14 are No or Yes response to dental status and sleep movements. Only the sum of the first 7 items to be analyzed (AIMS Movement Cluster score). Total score 0 to 28; higher score indicates greater severity.

Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total ScoreBaseline, Weeks 2, 6, 18, 26, ET

BPRS-A: 18-item clinician rated scale to assess somatic concern, anxiety, emotional withdrawal, disorganization, hallucinatory behavior, guilt feelings, suspiciousness, disorientation, tension, mannerisms, posturing, grandiosity, depressive mood, hostility, motor retardation, uncooperativeness, unusual thought content, blunted affect, excitement. Ratings anchored to improve consistency for single rater over time or between raters. Items rated on 7-point scale 0 (not present) to 6 (extremely severe). Total score=sum of items (range 0 to 108); higher scores indicate increased pathology.

Change From Baseline in Children's Global Assessment Scale (CGAS)Baseline, Weeks 2, 6, 18, 26, ET

CGAS: clinician-rated global assessment item for children based on symptoms and social functioning in home, school, and community settings. Scores on this single item range from 1 to 100 (higher levels indicate greater health) with descriptive anchors for every 10-point interval. Scores above 70 on this scale are considered within the "normal" range; lower score indicates need for increased supervision.

Change From Baseline in Child Health Questionnaire (CHQ)Baseline, Weeks 6 and 26, ET

CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.

Number of Subjects Per Response on the School Placement Questionnaire: School SituationBaseline, Weeks 6 and 26, ET

School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.

Number of Subjects Per Response on the School Placement Questionnaire: School AttendanceBaseline, Weeks 6 and 26, ET

School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.

Number of Subjects Per Response on the School Placement Questionnaire: Overall School PerformanceBaseline, Weeks 6 and 26, ET

School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇦

Vinnytsya, Ukraine

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