| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039626 |
|
| 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 |
1. To establish efficacy of oral ziprasidone compared with placebo in the treatment of adolescent subjects with schizophrenia, as measured by the change from baseline to Week 6in Brief Psychiatric Rating Scale - Anchored (BPRS-A) total score.
2. To evaluate the safety and tolerability of oral ziprasidone over 6 weeks in the treatment of adolescent subjects with schizophrenia. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate efficacy of oral ziprasidone as compared with placebo in the treatment of adolescent subjects with schizophrenia, as measured by
· Change from baseline in Positive and Negative Syndrome Scale (PANSS) - total score, positive and negative subscales.
· Change from baseline in Clinical Global Impression of Severity (CGI-S) score.
· Clinical Global Impression of Improvement (CGI-I) score.
2. To characterize the population pharmacokinetics and pharmacokinetics/pharmacodynamics (PK/PD) of oral ziprasidone in adolescent subjects with schizophrenia, including PK/PD analysis for efficacy (BPRS-A) and safety (QTc) measurements. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| 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 subject (male or female) must be between 13-17 (inclusive) years of age at screening.
3. The subject must have a primary diagnosis of schizophrenia as defined by DSM-IV criteria and confirmed by the KID-SCID.
4. The current symptoms must have been present for at least 7 days prior to Screening. Subjects with a first episode of psychosis are allowed.
5. At the screening and baseline visits, subjects must have a BPRS-A score ≥ 35 and a score of ≥ 4 on at least 1 of the following items: unusual thought content (ie, delusions), hallucinations, suspiciousness, or conceptual disorganization.
6. In the investigator’s opinion, the subject must be likely to benefit from antipsychotic therapy.
7. The subject must have a Body Mass Index (BMI) z-score between –1.65 and +1.65, inclusive.
8. The subject is willing and able to discontinue any medications that are prohibited in this study (see Concomitant Medications table, Section 5.5). Any such medications must be discontinued at least 4 half-lives (or 10 ten days, whichever is less) prior to the administration of double-blinded study medication.
9. 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:
a) Are instructed and agree to avoid pregnancy during the study.
b) Have a negative serum pregnancy test (β-HCG) at screening and baseline.
c) Use one of the following birth control methods:
· an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g. Norplant), transdermal hormonal contraceptive (e.g. Ortho-Evra), or an injectable contraceptive (e.g. 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, e.g., condom and/or diaphragm with spermicide while participating in the study.
· abstinence for at least 3 months before the start of the study and intention to abstain from sexual activity during the study period. |
|
| E.4 | Principal exclusion criteria |
Psychiatric :
1. Subjects who are clinically stable on treatment regimens that are being well tolerated.
2. Subjects with substance-induced psychotic disorder or whose behavioral disturbance is thought to be due to substance abuse.
3. Subjects with DSM-IV defined psychoactive substance or alcohol abuse/dependence (does not apply to nicotine or caffeine) within the preceding 1 month.
4. 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.
5. Subjects who are judged by the investigator as being at imminent risk of homicide
6. Subjects with significant mental retardation (i.e. IQ < 70) that would interfere with study conduct or with the interpretation of the study assessments.
7. Subjects with autism or pervasive developmental disorder.
General Medical;
8. Subjects with any serious, unstable illness including hepatic, renal, gastrointestinal, respiratory, cardiovascular, endocrinologic (including controlled or uncontrolled Type I diabetes), immunologic, hematologic, dermatological, oncological, or neurological disease (including any history of seizure or epilepsy).
9. 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 consciousness.
10. 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).
11. Subjects with uncorrected hypothyroidism or hyperthyroidism or whose thyroid function and medication regimen have been stable less than 1 month.
12. Subjects with any screening laboratory value that deviates significantly from the upper or lower limits of the normal reference range. SGOT and SGPT must be within 2 X and total bilirubin must be within 1.5 X times of the upper limits of the reference range.
13. Subjects with screening K+, Mg++ or Ca++ below the normal range.
14. Subjects with a history of chronic hepatitis, known serologic evidence of acute hepatitis or chronic hepatitis (positive HbsAg), or subjects with known hepatitis C antibodies and elevated LFTs.
15. Subjects known to be HIV positive.
16. Subjects with clinically significant hypokalemia or hypomagnesemia not corrected and stabilized by the addition of dietary supplements or some other corrective measure prior to Baseline.
17. Subjects with a history of significant cardiovascular disease, including conditions that have previously required treatment or acute evaluation, or significant concurrent cardiovascular disease, including uncontrolled hypertension (sitting diastolic pressure >90 mm Hg and/or sitting systolic pressure > 140 mm Hg with or without treatment), hypotension, congestive heart failure, or congenital heart disease.
18. Subjects with a history of cardiac arrhythmias, conduction abnormalities or known personal history of QT prolongation (including congenital long QT syndrome).
19. Subjects with a known genetic risk for prolonged QT syndrome
20. Subjects with a clinically significant ECG abnormality at Screening or Baseline
21. Subjects with persistent QTc (Fridericia) ≥ 460 msec at Screening or Baseline.
Medications;
22. Subjects taking any medications not allowed by the Concomitant Medication Table (Section 5.5). Medications should be avoided that may mask or exacerbate adverse effects, or have psychotropic properties which would exacerbate symptoms (eg, sympathomimetics) or obscure study drug effect (eg, antihistamines).
23. Subjects who have received clozapine within 12 weeks, a depot antipsychotic within 4 weeks or a monoamine oxidase inhibitor within 2 weeks prior to Baseline.
24. Subjects known by medical history or hospitalization records to have used phencyclidine within the 30 days prior to Screening.
25. Subjects requiring treatment with drugs which have been consistently observed to prolong the QT interval (see Section 5.5).
26. Subjects who received an investigational drug within 4 weeks of Baseline.
27. Subjects who received ziprasidone in a previous clinical trial.
28. Subjects known to be allergic to ziprasidone.
29. Subjects with history of antipsychotic-induced EPS that does not respond to antiparkinsonian medication.
30. Subjects with prior episode of neuroleptic malignant syndrome or prior hypersensitivity to antipsychotic agents.
31. Subjects with a history of non-responsiveness to ziprasidone after an adequate treatment period at a dose between 120-160 mg daily. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to Week 6 in Brief Psychiatric Rating Scale - Anchored (BPRS-A) total score. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 6 |
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