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.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005501-28-DE
• Date of registration: 29/08/2006
• Prospective Registration: No
• Primary sponsor: Pfizer Pharma GmbH
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 21/04/2006
• Target sample size: 276
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005501-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Sweden

Key inclusion & exclusion criteria

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 +2.00, 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 of the protocol). 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.
Patients 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 patient and/or alternative medication that is allowed by the protocol is available and appropriate for the patient. Psychotropic medications should be tapered down per accepted medical practice and the specific package insert instead of being abruptly discontinued.
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 (ß-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 (eg, Norplant®), transdermal hormonal contraceptive (eg, 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.
• abstinence for at least 3 months before the start of the study and intention to
abstain from sexual activity during the study period.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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. At the discretion of the investigator and after discussion with Pfizer, subjects with a positive urine drug screen may be eligible for admission.
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 (ie, 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). Subjects with a history of febrile seizures are eligible if no seizures have occurred during the last 3 years.
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. 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.
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. Subjects with an isolated increase of unconjugated bilirubin (Gilbert’s syndrome) are eligible.
13. 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.
14. Subjects known to be HIV positive.
15. 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.
Cardiovascular
16. 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 congen

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Schizophrenia
MedDRA version: 9.1 Level: LLT Classification code 10039626 Term: Schizophrenia

Intervention(s)

Trade Name: Zeldox 20 mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ziprasidone
CAS Number: 146939-27-7
Current Sponsor code: CP-88,059-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Zeldox 40 mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ziprasidone
CAS Number: 146939-27-7
Current Sponsor code: CP-88,059-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Zeldox 60 mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ziprasidone
CAS Number: 146939-27-7
Current Sponsor code: CP-88,059-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Zeldox 80 mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ziprasidone
CAS Number: 146939-27-7
Current Sponsor code: CP-88,059-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 1. To establish efficacy of oral ziprasidone compared to placebo in the treatment of adolescent subjects with schizophrenia, as measured by the change from baseline to Week 6 in 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.

Primary end point(s): Change from baseline to Week 6 in Brief Psychiatric Rating Scale - Anchored (BPRS-A) total score.

Secondary Objective: 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.

Secondary ID(s)

2005-005501-28-SE

A1281134