Safety And Efficacy Of Ziprasidone In Adolescents With Schizophrenia

Six Week, Double-Blind, Placebo Controlled Phase III Trial Evaluating The Efficacy, Safety And Pharmacokinetics Of Flexible Doses Of Oral Ziprasidone In Adolescent Subjects With Schizophrenia

The purpose of this study is to determine if flexibly-dosed ziprasidone is safe and effective for the treatment of adolescents (ages 13-17) with schizophrenia

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: placebo; Drug: Ziprasidone oral capsules

Detailed Description

Termination Reason: 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.

• Study Type: Interventional
• Enrollment (Actual): 284
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia
      • Pfizer Investigational Site
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Pfizer Investigational Site
• Costa Rica
  • San Jose, Costa Rica
    • Pfizer Investigational Site
• India
  • Andhra Pradesh
    • Vijaywada, Andhra Pradesh, India, 520 002
      • Pfizer Investigational Site
  • Andra Pradesh/India
    • Visakhapatnam, Andra Pradesh/India, India, 530 017
      • Pfizer Investigational Site
  • Guj
    • Ahmedabad, Guj, India, 380015
      • Pfizer Investigational Site
  • Karnataka
    • Mangalore, Karnataka, India, 575001
      • Pfizer Investigational Site
  • Maharashtra
    • Aurangabad, Maharashtra, India, 431 005
      • Pfizer Investigational Site
    • Mumbai, Maharashtra, India, 400 058
      • Pfizer Investigational Site
    • Pune, Maharashtra, India, 411 001
      • Pfizer Investigational Site
    • Pune, Maharashtra, India, 411 046
      • Pfizer Investigational Site
  • Punjab
    • Ludhiana, Punjab, India, 141001
      • Pfizer Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 003
      • Pfizer Investigational Site
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Pfizer Investigational Site
  • Kuala Lumpur, Malaysia, 50603
    • Pfizer Investigational Site
  • Kuala Lumpur, Malaysia, 55100
    • Pfizer Investigational Site
  • Kelantan
    • Kubang Kerian, Kelantan, Malaysia, 16150
      • Pfizer Investigational Site
• Peru
  • Lima, Peru, L13
    • Pfizer Investigational Site
  • Lima, Peru, L41
    • Pfizer Investigational Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Pfizer Investigational Site
  • Khotkovo, Moscow Region, Russian Federation, 142601
    • Pfizer Investigational Site
  • Lipetsk Region, Russian Federation, 399313
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 115522
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 107076
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 117152
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 127473
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 143300
    • Pfizer Investigational Site
  • Nizhniy Novgorod, Russian Federation, 603155
    • Pfizer Investigational Site
  • Saratov, Russian Federation, 410012
    • Pfizer Investigational Site
  • Saratov, Russian Federation, 410060
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 192019
    • Pfizer Investigational Site
  • Tver, Russian Federation, 170005
    • Pfizer Investigational Site
  • Yaroslavl, Russian Federation, 150003
    • Pfizer Investigational Site
• Singapore
  • Singapore, Singapore, 229899
    • Pfizer Investigational Site
  • Singapore, Singapore, 539747
    • Pfizer Investigational Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Pfizer Investigational Site
  • Dnipropetrovsk, Ukraine, 49115
    • Pfizer Investigational Site
  • Donetsk, Ukraine, 83037
    • Pfizer Investigational Site
  • Kharkiv, Ukraine, 61068
    • Pfizer Investigational Site
  • Kyiv, Ukraine, 04655
    • Pfizer Investigational Site
  • Lugansk, Ukraine, 91045
    • Pfizer Investigational Site
  • Lviv, Ukraine, 79021
    • Pfizer Investigational Site
  • Odessa, Ukraine, 65006
    • Pfizer Investigational Site
  • Poltava, Ukraine, 36006
    • Pfizer Investigational Site
  • Vinnytsya, Ukraine, 21005
    • Pfizer Investigational Site
  • Crimea
    • Simferopol, Crimea, Ukraine, 95006
      • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35294
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35294-4400
      • Pfizer Investigational Site
  • California
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
    • Stanford, California, United States, 94305
      • Pfizer Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pfizer Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Pfizer Investigational Site
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Pfizer Investigational Site
    • Fort Lauderdale, Florida, United States, 33301
      • Pfizer Investigational Site
    • North Miami, Florida, United States, 33161
      • Pfizer Investigational Site
    • Orange City, Florida, United States, 32763
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33613
      • Pfizer Investigational Site
    • Tavares, Florida, United States, 32778
      • Pfizer Investigational Site
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • Pfizer Investigational Site
    • Tucker, Georgia, United States, 30084
      • Pfizer Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pfizer Investigational Site
  • Illinois
    • Des Plaines, Illinois, United States, 60016
      • Pfizer Investigational Site
    • Oakbrook Terrace, Illinois, United States, 60181
      • Pfizer Investigational Site
    • Schaumburg, Illinois, United States, 60194
      • Pfizer Investigational Site
  • Maryland
    • Pikesville, Maryland, United States, 21208
      • Pfizer Investigational Site
    • Towson, Maryland, United States, 21204
      • Pfizer Investigational Site
    • Towson, Maryland, United States, 21286
      • Pfizer Investigational Site
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Pfizer Investigational Site
  • Mississippi
    • Meridian, Mississippi, United States, 39301
      • Pfizer Investigational Site
  • Missouri
    • Bridgeton, Missouri, United States, 63044-2588
      • Pfizer Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Pfizer Investigational Site
    • Omaha, Nebraska, United States, 68131
      • Pfizer Investigational Site
  • New York
    • Buffalo, New York, United States, 14215
      • Pfizer Investigational Site
    • Buffalo, New York, United States, 14209
      • Pfizer Investigational Site
    • Rochester, New York, United States, 14618
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45229
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45224
      • Pfizer Investigational Site
    • Cleveland, Ohio, United States, 44106
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73101
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73116
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73107
      • Pfizer Investigational Site
  • Texas
    • Arlington, Texas, United States, 76011
      • Pfizer Investigational Site
    • DeSoto, Texas, United States, 75115
      • Pfizer Investigational Site
    • Plano, Texas, United States, 75093
      • Pfizer Investigational Site
  • Washington
    • Bothell, Washington, United States, 98011
      • Pfizer Investigational Site
    • Spokane, Washington, United States, 99204
      • Pfizer Investigational Site
    • Spokane, Washington, United States, 99216
      • Pfizer Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Pfizer Investigational Site
    • West Allis, Wisconsin, United States, 53227
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia: Current symptoms were to be present for at least 7 days before screening.
• At the Screening and Baseline visits, subjects must have had a Brief Psychiatric Rating Scale - Anchored score ≥35 and a score of ≥4 on at least 1 of the following items: unusual thought content (i.e., delusions), hallucinations, suspiciousness, or conceptual disorganization.
• Age 13 - 17 years

Exclusion Criteria:

• Imminent risk of suicide or homicide, as judged by the site investigator
• Any history of serious or unstable medical illness, including risk for QT prolongation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2.0	Drug: placebo; Placebo matching the oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength or matching placebo. Subjects will be dosed daily for 6 weeks using a flexible dose design with a minimal dose range of 40mg twice a day (BID) to a maximum dose range of 80 mg BID. For subjects weighing <45 kg, the doses will range from 20 mg BID to 40 mg BID.
Active Comparator: 1.0	Drug: Ziprasidone oral capsules; Oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength or matching placebo. Subjects will be dosed daily for 6 weeks using a flexible dose design with a minimal dose range of 40mg BID to a maximum dose range of 80 mg BID. For subjects weighing <45 kg, the doses will range from 20 mg BID to 40 mg BID.; Other Names: Geodon, Zeldox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score at Week 6	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, and excitement. Ratings anchored to improve consistency for a 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.	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 6	CGI-S: single-item clinician rated scale to rate the severity of a subject's illness over time. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects); higher score indicates more affected.	Baseline, Week 6
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 6	PANSS: 30-item clinician-rated scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Items scored on anchored Likert scale rated 1 (absent symptoms) to 7 (extreme); scores above 1 indicate clinical symptom is present; scores from 2 to 7 indicate increased severity. Total score range 30 to 210: higher score indicates greater severity.	Baseline, Week 6
Change From Baseline in PANSS: Positive and Negative Subscales at Week 6	PANSS: 30-item clinician-rated scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Items scored on anchored Likert scale rated 1 (absent symptoms) to 7 (extreme); scores above 1 indicate clinical symptom is present; scores from 2 to 7 indicate increased severity. Total score range 30 to 210: higher score indicates greater severity.	Baseline, Week 6
Clinical Global Impression of Improvement (CGI-I) Score at Week 6	CGI-I: single-item clinician rated scale used to assess the subject's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.	Baseline, Week 6
Change From Baseline in Children's Global Assessment Scale (CGAS)	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.	Baseline, Week 2, Week 4, Week 6, Early termination (ET)
Change From Baseline in Child Health Questionnaire (CHQ)	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.	Baseline, Week 6, ET
Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score	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.	Baseline, Week 1 through Week 6
Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score	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.	Baseline, Week 1 through Week 6
Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13	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. Suicide Ideation (Item 13) detects changes in suicidality over time. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).	Baseline, Week 1 through Week 6
Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Impaired Schoolwork Item 1	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 resolved by using most impaired rating given by valid informant. Impaired Schoolwork (Item 1) assesses school function for the subgroup of subjects reported to be in school. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).	Baseline, Week 2, Week 6
Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales	A computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, and sustained attention. A computerized 7-point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. The Neurocognitive index score was derived from subtest scores per an algorithm. The 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).	Baseline, Week 6, ET
Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index	A computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, and sustained attention. A computerized 7-point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. The Neurocognitive index score was derived from subtest scores per an algorithm. The 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).	Baseline, Week 6, ET
Change From Baseline in Movement Disorder Scales: Simpson-Angus Rating Scale (SARS)	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.	Baseline, Week 1 through Week 6
Change From Baseline in Movement Disorder Scales: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item	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.	Baseline, Week 1 through Week 6
Change From Baseline in Movement Disorder Scales: Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score	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.	Baseline, Week 1 through Week 6
Number of Subjects Per Response on the School Placement Questionnaire: School Situation	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.	Baseline, Week 2, Week 6, ET
Number of Subjects Per Response on the School Placement Questionnaire: School Attendance	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.	Baseline, Week 2, Week 6, ET
Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance	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.	Baseline, Week 2, Week 6, ET

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Findling RL, Cavus I, Pappadopulos E, Vanderburg DG, Schwartz JH, Gundapaneni BK, DelBello MP. Ziprasidone in adolescents with schizophrenia: results from a placebo-controlled efficacy and long-term open-extension study. J Child Adolesc Psychopharmacol. 2013 Oct;23(8):531-44. doi: 10.1089/cap.2012.0068. Epub 2013 Oct 10.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: November 21, 2005
• First Submitted That Met QC Criteria: November 21, 2005
• First Posted (Estimate): November 22, 2005

Study Record Updates

• Last Update Posted (Actual): March 25, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Adolescent Subjects With Schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Ziprasidone
• Other Study ID Numbers: A1281134