Safety And Tolerability Of Ziprasidone In Adolescents With Schizophrenia

This study has been terminated.
(Please see Detailed Description for termination reason.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00265382
First received: December 12, 2005
Last updated: December 2, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Ziprasidone oral capsules
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 26-Week Open-Label Extension Study Evaluating The Safety And Tolerability Of Flexible Doses Of Oral Ziprasidone In Adolescent Subjects With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Number of Subjects With Change From Baseline to Each Pubertal Stage of Development as Assessed by the Tanner Adolescent Pubertal Self Assessment [ Time Frame: Baseline, Week 26, Early Termination (ET) ] [ Designated as safety issue: Yes ]
    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 Score [ Time Frame: Baseline, Weeks 2, 6, 18, 26, ET ] [ Designated as safety issue: Yes ]
    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 Score [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ] [ Designated as safety issue: Yes ]
    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): Subscales [ Time Frame: Baseline, Weeks 6 and 26, ET ] [ Designated as safety issue: Yes ]
    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 Index [ Time Frame: Baseline, Weeks 6 and 26, ET ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ] [ Designated as safety issue: Yes ]
    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 Item [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ] [ Designated as safety issue: Yes ]
    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 Score [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ] [ Designated as safety issue: Yes ]
    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 Score [ Time Frame: Baseline, Weeks 2, 6, 18, 26, ET ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Weeks 2, 6, 18, 26, ET ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Weeks 6 and 26, ET ] [ Designated as safety issue: No ]
    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 Situation [ Time Frame: Baseline, Weeks 6 and 26, ET ] [ Designated as safety issue: No ]
    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 Attendance [ Time Frame: Baseline, Weeks 6 and 26, ET ] [ Designated as safety issue: No ]
    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 Performance [ Time Frame: Baseline, Weeks 6 and 26, ET ] [ Designated as safety issue: No ]
    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.


Enrollment: 221
Study Start Date: June 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Open Drug: Ziprasidone oral capsules
Study medications will include oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength. Subjects will be dosed daily for 26 weeks using a flexible dose design with a minimal dose range of 20mg bid to a maximum dose range of 80 mg bid.
Other Name: Geodon, Zeldox

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.

  Eligibility

Ages Eligible for Study:   13 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00265382

  Show 68 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00265382     History of Changes
Other Study ID Numbers: A1281135
Study First Received: December 12, 2005
Results First Received: April 16, 2010
Last Updated: December 2, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Adolescent Subjects

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Ziprasidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on August 28, 2014