Submitted by: Yvette Lopez 2019-05-06 01:03:08 Last Updated by: Yvette Lopez 2019-07-11 10:44:43 Export to PDF

A PHASE 3, MULTICENTER, FOUR-WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP EFFICACY AND SAFETY TRIAL OF FLEXIBLE DOSES OF ORAL ZIPRASIDONE IN CHILDREN AND ADOLESCENTS WITH BIPOLAR I DISORDER (CURRENT OR MOST RECENT EPISODE MANIC)

PHRR190517-002124

A1281198

2019-CT0479

A PHASE 3, MULTICENTER, FOUR-WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP EFFICACY AND SAFETY TRIAL OF FLEXIBLE DOSES OF ORAL ZIPRASIDONE IN CHILDREN AND ADOLESCENTS WITH BIPOLAR I DISORDER (CURRENT OR MOST RECENT EPISODE MANIC)

This will be a Phase 3, multicenter, 4-week, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy, safety, and tolerability of flexibly dosed ziprasidone compared with placebo for the treatment of Bipolar I Disorder (current or most recent episode manic) in children and adolescents aged 10 to 17 years (inclusive). Ziprasidone (or placebo) will be administered as oral capsules given twice daily (BID) with food. Ziprasidone (or placebo) will be titrated over the first 7-14 days of treatment, and then flexibly dosed through the end of the double-blind treatment period (Week 4, Day 29). Approximately 180 subjects (90 ziprasidone: 90 placebo) will be recruited from approximately 60 -70 United States (US) sites.  It is estimated that approximately 300 subjects will be required to be screened to achieve this enrollment target with an anticipated screen failure rate of approximately 40%. The study will begin with a screening visit to determine subject eligibility, followed by a 1-14 day period to allow for wash-out of exclusionary medications. Subjects who qualify will be randomized at baseline to receive either double-blind oral ziprasidone or placebo (randomization ratio 1:1). Eligible subjects will remain in the treatment period for 4 weeks. After completion of the treatment phase, subjects will return for a post-treatment follow-up visit at week 5. Subjects who complete the study or who terminate early may be eligible for continuation of treatment in the open label extension study A1281201. 

Start Date Duration in Months Target Completion Date Actual Completion Date
2019-09-30 1 2019-10-30 2019-05-09

Pending

Awaiting approval and site activation

Institution Classification Region LTO #
Pfizer Inc. Private Business NCR
Institution Classification Region LTO #
ICON Clinical Research Services Inc. Private Business NCR CDRR-NCRCRO-10
Institution Amount Region
Pfizer Inc. N/A NCR
Name E-Mail Phone Number Postal Address
Yvette Lopez Yvette.Lopez@iconplc.com 6322305745 ICON Clinical Research Services Philippines Inc
Name E-Mail Phone Number Postal Address
Yvette Lopez Yvette.Lopez@iconplc.com 6322305745 ICON Clinical Research Services Philippines Inc
Name Expertise Affiliation
Evelyn G. Gapuz, MD Psychiatry Philippine General Hospital
Aida Muncada, MD Psychiatry National Center for Mental Health
Elizabeth Rondain, MD Psychiatry Makati Medical Center
Project Location Institutional Ethics Review Board
Philippine General Hospital Philippine General Hospital Ethics Review Board
National Center for Mental Health National Center for Mental Health Institutional Review Board
Makati Medical Center Makati Medical Center Institutional Review Board

Treatment of children and adolescents aged 10-17 with Bipolar I Disorder (current or most recent episode manic) treatment of children and adolescents aged 10-17 with Bipolar I Disorder (current or most recent episode manic)

The primary endpoint of the study is the change from baseline to Week 4 in the Young Mania Rating Scale (YMRS) total score.

The key secondary endpoint of the study is the change from baseline to Week 4 in the Clinical Global Impression of Severity (CGI-S) score.

 Other secondary endpoints include the:

  •  Change from baseline to Weeks 1, 2, and 3 in the  Young Mania Rating Scale (YMRS) total score;
  •  Change from baseline to Weeks 1, 2 and 3 in the Clinical Global Impression of Severity (CGI-S) score;
  •  Clinical Global Impression of Severity (CGI-I) scores at Weeks 1, 2, 3, and 4.

Pending

  • Philippines

Clinical Trial

20190109112753

2019-04-12

Date Amendment Classification Reason
2019-06-07 Amendments related to the protocol Design of trial

Inclusion Criteria

  1. Evidence of personally signed and dated informed consent document by the legal representative and an assent document by the subject indicating that the subject and a legal representative have been informed of all pertinent aspects of the stud
  2.  Subjects and their legal guardians who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study
  3.  In-patient and/or out-patient male and female subjects aged 10-17 (inclusive) at
  4. Primary diagnosis of Bipolar I Disorder (current or most recent episode manic), as defined by DSM-V criteria and confirmed by the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS). Current symptoms supporting the diagnosis must have been present for at least 7 days prior to
  5.  YMRS score ³17 at the screening and baseline visits.
  6.  In the investigator’s opinion, the subject must be likely to benefit from therapy with an atypical antipsychotic
  7. Body Mass Index (BMI) z-score between –1.65 and +2.00, inclusive.
  8.  Subject must be willing and able to discontinue any medications that are prohibited in this study. Any such medications must be discontinued (according to the timeframes in Section 5.5) prior to baseline.

 Subjects who are receiving prohibited medications are to be considered for the protocol only if discontinuation of the medication does not compromise the welfare of the subject and/or alternative medication that is allowed by the protocol is available and appropriate for the subject.

 Psychotropic medications should be tapered down per accepted medical practice and the specific package insert instead of being abruptly discontinued

 If psychotherapy has been ongoing for 3 months prior to the screening visit, it can be continued during the study provided there is no increase in the frequency or duration of the psychotherapy or change in the type of psychotherapy being provided.

      9.  All male and female subjects who are sexually active and/or their legal guardians, as appropriate, must agree that a highly effective method of contraception be used throughout the study and for 28 days after the last dose of assigned treatment.

Exclusion Criteria

Subjects presenting with any of the following will not be included in the study:

  1.  Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the t
  2. Subjects who are clinically stable on treatment regimens that are being well tolerated.
  3.  Subjects with substance-induced psychotic disorder or whose behavioral disturbance is thought to be due to substance
  4.  Subjects with DSM-V defined Substance Use Disorder (including psychoactive substance or alcohol use disorders) within the preceding 1 month of screening (does not apply to nicotine or caffeine).
  5.  Subjects who are judged by the investigator as being at imminent risk of suicide.
  6.  Subjects who are judged by the investigator as being at imminent risk of homicide.
  7.  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 any of the screening instruments or other screening information based on the investigator’s judgment indicate:
    • A suicide ideation associated with actual intent and a method or plan at any time in their lifetime such that a positive response (‘Yes’) is made on items 4 or 5 of the suicidal ideation subscale of the C-SSRS; or
    • Any lifetime history of suicide behaviors such that a determination of ‘yes’ is made to any of the suicide behavior items of the C-SSRSSubjects with significant Intellectual Disability (ie, Intelligence Quotient (IQ) <70) that would interfere with study conduct or with the interpretation of the study assessments
  8. Subjects with Autism Spectrum Disorder (including autistic disorder, Rett syndrome, childhood disintegrative disorder, pervasive developmental disorder – not otherwise specified (PDD-NOS), Asperger syndrome).
  9. Subjects with Disruptive Mood Dysregulation
  10.  Subjects with schizophrenia, schizoaffective disorder, schizophreniform disorder, or delusional disorder.
  11.  Other severe acute or chronic medical or psychiatric condition 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.
  12.  Subjects with controlled or uncontrolled Type 1 diabetes.
  13.  Subjects with Type 2 diabetes unless diagnosed ≥6 months prior to screening and on a stable, well controlled treatment regimen (ie, diet and/or oral hypoglycemic agents; insulin use is considered exclusionary).
  14. Subjects with a history of seizure or epilepsy

Subjects with a history of febrile seizures are eligible if no seizures have occurred during the last 3 years.

15. Subjects with a history of syncopal episodes (sudden loss of consciousness with loss of postural tone and not preceded by a pre-syncopal phase) or unexplained loss of

 Subjects with a history of occasional syncopes of probable vasovagal origin (onset not sudden but preceded by a pre-syncopal phase, presence of predisposing factors such as blood sampling procedure, standing, hot shower, hair curling, etc) are eligible.

16. Subjects with any medical condition or dietary habit that has a significant potential to alter the absorption of the study drug; or subjects taking any medication that may alter drug absorption (eg, anorexia nervosa, bulimia, chronic use of laxatives).

 17. Subjects with uncorrected hypothyroidism or hyperthyroidism or whose thyroid function and medication regimen have been stable less than 1 month prior to screening.

 18. Alanine aminotransferase (ALT)/ Aspartate aminotransferase (AST) values ≥2x and total bilirubin values ≥1.5x the upper limits of normal.

 Subjects with an isolated increase of unconjugated bilirubin (Gilbert’s syndrome) are eligible.

 19. Subjects with a history of chronic hepatitis, known serologic evidence of acute hepatitis or chronic hepatitis (positive hepatitis B virus surface antigen (HbsAg)), or subjects with known hepatitis C antibodies and elevated

 20. Subjects known to be Human Immunodeficiency Virus (HIV)

 21. Subjects with clinically significant hypokalemia or hypomagnasemia not corrected and stabilized by the addition of dietary supplements or some other corrective measure prior to baseline.

 22. Subjects with a history of significant cardiovascular disease, including conditions that have previously required treatment or acute evaluation, or significant concurrent cardiovascular disease, including hypotension, congestive heart failure, or congenital heart

 Non-clinically significant sinus bradycardia or sinus tachycardia will not be considered significant medical illnesses and would not exclude a subject from the study.

 Isolated atrial septal defect (ASD), ventricular septal defect (VSD, or patent ductus arteriosus (PDA) will not be considered significant medical illnesses if they are surgically corrected.

 23. Subjects with a history of cardiac arrhythmias, conduction abnormalities or known personal history of QT prolongation (including congenital long QT syndrome).

 24. Subjects with a known genetic risk for prolonged QT syndrome

 25. Subjects with a clinically significant ECG abnormality at screening or baseline.

26. Subjects with a QTc (Fridericia) ³450 msec at screening or baseline, which is still prolonged on repeat ECG.

27. Subjects taking any medications that are prohibited.

28. Subjects who are taking or have previously received clozapine.

29. Use of a depot antipsychotic within 4 weeks, or a monoamine oxidase inhibitor, Abilify® (aripiprazole) or Prozac® (fluoxetine) within 2 weeks prior to baseline.

30. Subjects known by medical history or hospitalization records to have used phencyclidine within the 30 days prior to screening.

 31. Subjects requiring treatment with drugs which have been consistently observed to prolong the QT interval (see Section 5.5).

 32. Subjects with history of antipsychotic-induced EPS that does not respond to anti-parkinsonian medication.

 33. Subjects with a prior episode of neuroleptic malignant syndrome or prior hypersensitivity to antipsychotic agents.

 34. Subjects known to be allergic to ziprasidone

 35. Subjects with a history of non-responsiveness to ziprasidone after an adequate treatment period at a dose between 40-80 mg daily for subjects weighing

 36. Subjects currently receiving ziprasidone 30 days prior to

 37. Participation in other studies involving investigational drug(s) (Phase 1-4) within 30 days before the current study begins and/or during study participation.

 38. Pregnant females; breastfeeding females; males and females who are sexually active who are not using highly effective contraception or not agreeing to continue highly effective contraception for 28 days after last dose of assigned treatment. If a subject is not sure whether they might be pregnant at the time of screening, ie, they have had unprotected sex within the last 2 weeks prior to screening, then that subject would be required to have 2 negative pregnancy tests two weeks apart before they could receive study drug.

 39. Siblings, or other subjects living in the same home or having the same caregiver during the same enrollment period.

Observational

Unspecified

Unspecified

Randomized

Double Blind

The study will begin with a screening visit to determine subject eligibility, followed by a 1-14 day period to allow for wash-out of exclusionary medications. Subjects who qualify will be randomized at baseline to receive either double-blind oral ziprasidone or placebo (randomization ratio 1:1).

Parallel

Primary Objectives

 The primary objectives of the study are:

  1.  To assess the efficacy of oral ziprasidone compared with placebo in the treatment of children and adolescents aged 10-17 with Bipolar I Disorder (current or most recent episode manic), as measured by the change from baseline to Week 4 in the Young Mania Rating Scale (YMRS) total score
  2.  To evaluate the safety and tolerability of oral ziprasidone over 4 weeks in the treatment of children and adolescents with Bipolar I Disorder (current or most recent episode manic).

Phase III

10

Unspecified

Unspecified

30 Sep 2019

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