E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Mental condition marked by alternating periods of elation and depression |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of oral ziprasidone (40-80 milligram [mg] twice a day[BID]) during long-term, open-label administration in children and adolescents with Bipolar I Disorder - Single Manic Episode; Bipolar I Disorder – Most Recent Episode Manic, or Bipolar I Disorder – Most Recent Episode Mixed |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject and the authorized legal representative must understand the nature of the study and be able to comply with protocol requirements. The representative must sign an Informed Consent Document and the subject must provide Written Assent.
2. The subjects must have received study medication in Study A1281132. In general, subjects should have completed at least 3 weeks of double-blind treatment before entering this open-label extension. However, subjects who have insufficient treatment response and have reached their maximum tolerated dose may enroll in the open-label extension as early as 1 week after the end of their titration.
3. In the investigator’s opinion, the subject must be likely to continue to benefit from antipsychotic therapy and must have been free from any clinically significant safety concerns during the preceding double-blind study (ie, in the opinion of the investigator, the benefits that the subject is likely to derive from continued participation must outweigh the risks).
4.Females of childbearing potential may be included provided that they are not pregnant, not nursing, and are practicing effective contraception and meet all of the following criteria:
• Are instructed and agree to avoid pregnancy during the study.
• Have a negative serum pregnancy test (-hCG) at the baseline visit.
• Use one of the following birth control methods:
• an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (eg, Norplant), transdermal hormonal contraceptive (Ortho-Evra), or an injectable contraceptive (eg, Depo-Provera) for at least one month prior to entering the study and will continue its use throughout the study; or
• a barrier method of contraception, eg, condom and/or diaphragm with spermicide while participating in the study; or abstinence during the preceding double-blind study and intention to abstain from sexual activity throughout this extension study. |
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E.4 | Principal exclusion criteria |
1. Subjects who experienced a serious adverse event considered related to study medication during the preceding double-blind trial.
2. Subjects who experienced cardiac arrhythmias, conduction abnormalities, or QTc prolongation (confirmed and persisting QT interval corrected using Fridericia’s formula (QTcF) greater than or equal to () 460 millisecond (msec) or increase from baseline of QTcF 60 msec) during the preceding study (subjects with an increase in QTcF of 60 msec but with QTcF less than or equal to (≤) 400 msec will be reviewed on a case-by-case basis by the sponsor for possible inclusion in the study).
3. Subjects requiring any medications not allowed by the Concomitant Medication Table.
4. Subjects who require treatment with drugs that are known to consistently prolong the QT interval.
5. Subjects with a rating of 7 on the single Suicidal Ideation item (item #13) from the CDRS-R, or who are otherwise 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 during the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Young Mania Rating Scale (YMRS) Total Score Change From Baseline
- Clinical Global Impression of Severity (CGI-S) Change From Baseline
- Incidence of Lab Abnormalities
- Change in Low-Density Lipoprotein (LDL) Cholesterol and Fasting Cholesterol
- Change in Hormones
- Mean Change From Baseline in Supine Systolic Blood Pressure
- Mean Change From Baseline in Supine Diastolic Blood Pressure
- Mean Change From Baseline in Supine Pulse Rates
- Mean Change From Baseline in Standing Systolic Blood Pressure
- Mean Change From Baseline in Standing Diastolic Blood Pressure
- Mean Change From Baseline in Standing Pulse Rates
- Mean Change From Baseline for Body Weight
- Mean Change From Baseline for Body Mass Index (BMI) Z-Score
- Body Mass Index (BMI) Z-score Frequency
- Body Mass Index (BMI) Z-score Frequency
- Mean Change From Baseline for QTcF Intervals
- Frequency of Largest Categorical Increases in QTcF for Males
- Frequency of Largest Categorical Increases in QTcF for Females
- Frequency of Largest Categorical Increases in QTcF - All Subjects |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- baseline and 26 Weeks; 26 Weeks Last Observation Carried Forward (LOCF)
- baseline and 26 Weeks; 26 Weeks LOCF
- Week 26
- Week 6, Week 26
- Week 6, Week 26
- Week 6, Week 26
- Week 1 through Week 26
- Week 1 through Week 26
- Week 1 through Week 26
- Week 1 through Week 26
- Week 1 through Week 26
- Week 1 through Week 26
- Week 6, Week 26
- Week 6, 26, early termination
- Week 6
- Week 26
- Baseline to Week 26 (end of study)
- Week 26 (end of study)
- Week 26 (end of study)
- Week 26 (end of study) |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 8 |