Clinical trial NCT03768726: Extension Study Evaluating The Safety And Tolerability Of Flexible Doses Of Oral Ziprasidone In Children And Adolescents With Bipolar I Disorder
Official title: 26-WEEK OPEN-LABEL EXTENSION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF FLEXIBLE DOSES OF ORAL ZIPRASIDONE IN CHILDREN AND ADOLESCENTS WITH BIPOLAR I DISORDER (MOST RECENT EPISODE MANIC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bipolar Disorder
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-12-07
Enrollment: 23
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Subjects would completed A1281198 will be transitioned under double blind conditions to 26 weeks of treatment with flexibly dosed opened label ziprasidone.
Primary purpose: TREATMENT

Brief summary: This 26-week open-label extension study is designed to provide information on the safety and tolerability of oral ziprasidone (20-80 mg BID (twice daily) with meals) during long-term administration in children and adolescents with Bipolar I Disorder (current or most recent episode manic).

Detailed description: Study A1281201 is a 6 month, open label extension study of the ongoing double blind, randomized, placebo controlled study of ziprasidone in pediatric Bipolar Disorder (Study A1281198). Study A1281201 will enroll adolescents aged 10 to 17 years with Bipolar I Disorder who have participated in double blind Study A1281198. In order to be enrolled in this open label extension trial, subjects must have met the enrollment criteria for Study A1281198, and must meet the inclusion and exclusion criteria for Study A1281201 at the extension study Baseline visit (last visit in the double blind study).

The purpose of adding this extension study to the ongoing Geodon pediatric bipolar program is to obtain additional longer term safety data in children and adolescents with Bipolar I disorder treated with ziprasidone.

Eligibility criteria: Inclusion Criteria

* Evidence of personally signed and dated informed consent document by the legal representative and an assent document by the subject .
* Subjects and their legal guardians who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* The subjects must have received investigational product in Study A1281198 before entering this open label extension.
* In the investigator's opinion, the subject must be likely to benefit from antipsychotic therapy .
* All fertile male subjects and female subjects of childbearing potential who are sexually active and/or their legal guardians, as appropriate, must agree that a highly effective method of contraception

Exclusion Criteria

* Any subjects from the preceding double blind trail who experienced a serious adverse event which required study medication to be discontinued and the subject to be withdrawn from the study. Subjects who experienced cardiac arrhythmias, conduction abnormalities, or QTc prolongation (confirmed and persistent Fridericia's correction (QTcF) \>480 msec or increase from baseline QTcF \>60 msec) during the preceding study.
* Subjects requiring any medications not allowed by the Concomitant Medication Table 12 (see "Concomitant Treatment(s)").
* Subjects who require treatment with drugs that are known to consistently prolong the QT interval (see Concomitant Medication Table 12).
* Subjects who are judged by the investigator as being at imminent risk of suicide.
* Subjects living in the same home as another study participant or having the same caregiver during the same enrollment period (Such subjects can be enrolled in the study at different times but may not be in the study at the same time).
* Subjects should be excluded or a risk assessment should be done to verify that it is safe for the subject to participate in the trial if the subject's responses on the C SSRS or other information based on the investigator's judgment indicate:

  * Suicide ideation associated with actual intent and a method or plan such that a positive response ('Yes') is made on items 4 or 5 of the suicidal ideation subscale of the C SSRS; or
  * Any suicide behaviors such that a determination of 'yes' is made to any of the suicide behavior items of the C SSRS.
* Pregnant female subjects, breastfeeding female subjects.
* Participation in other studies other than the preceding Study.
* Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: A1281201: Day 1 up to 35 days after last dose of study medication (maximum up to 31 Weeks)
Secondary outcomes:
measure: Number of Participants With Laboratory Abnormalities
timeFrame: A1281201: Day 1 up to 1 Week after last dose of study medication (maximum up to 27 Weeks)
measure: Number of Participants With Physical Examination Abnormalities at Baseline and Week 26
timeFrame: Baseline (last measurement from A1281198), Week 26 of A1281201
measure: Change From Baseline in Blood Pressure at Week 1, 2, 4, 6, 10, 14, 18, 22, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Pulse Rate at Week 1, 2, 4, 6, 10, 14, 18, 22, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Height and Waist Circumference at Week 6, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 6, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Body Weight at Week 6, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 6, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Body Mass Index (BMI) at Week 6, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 6, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Body Mass Index (BMI) Z-score at Week 6, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 6, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Heart Rate at Day 1, Week 1, 2, 4, 6, 14, 22, 26 and Follow-up Visit
timeFrame: Baseline of A1281198, Day 1 (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 14, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Electrocardiogram (ECG) Parameters at Day 1, Week 1, 2, 4, 6, 14, 22, 26 and Follow-up Visit
timeFrame: Baseline of A1281198, Day 1 (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 14, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Global Clinical Assessment of Akathisia Subscale Score of Barnes Akathisia Rating Scale (BAS) at Week 1, 2, 4, 6, 10, 14, 18, 22, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Movement Cluster Subscale Score of Abnormal Involuntary Movement Scale (AIMS) at Week 1, 2, 4, 6, 10, 14, 18, 22, 26 and Follow-up Visit
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26, and Follow-up Visit (1 Week from last dose of study medication, anytime maximum up to Week 27)
measure: Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Week 26
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 26
measure: Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 1, 2, 6, 14, 22, 26
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 6, 14, 22, 26
measure: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 1, 2, 4, 6, 10, 14, 18, 22, 26
measure: Change From Baseline in Children's Global Assessment Scale (CGAS) Total Score at Week 26
timeFrame: Baseline (last measurement from A1281198), A1281201: Week 26
Other outcomes:
Locations:
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Fayetteville
country: United States
facility: Inova Clinical Trials and Research Centre
state: Georgia
city: Smyrna
country: United States
facility: Attalla Consultants, LLC dba Institute for Behavioral Medicine
state: Georgia
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Plano
country: United States
facility: AIM Trials, LLC
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of the Woodlands
state: Texas
city: Everett
country: United States
facility: Eastside Therapeutic Resource Inc dba Core Clinical Research
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Atkinson S, Bachinsky M, Raiter Y, Abreu P, Ianos C, Chappell P, Findling RL. 26-Week Open-Label Extension Study Evaluating the Safety and Tolerability of Flexible Doses of Oral Ziprasidone in Children and Adolescents with Bipolar I Disorder (Most Recent Episode Manic). J Child Adolesc Psychopharmacol. 2022 Oct;32(8):453-458. doi: 10.1089/cap.2022.0030.
citation: Findling RL, Atkinson S, Bachinsky M, Raiter Y, Abreu P, Ianos C, Chappell P. Efficacy, Safety, and Tolerability of Flexibly Dosed Ziprasidone in Children and Adolescents with Mania in Bipolar I Disorder: A Randomized Placebo-Controlled Replication Study. J Child Adolesc Psychopharmacol. 2022 Apr;32(3):143-152. doi: 10.1089/cap.2021.0121. Epub 2022 Apr 7.