| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Schizophrenia and Schizoaffective Disorder |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039635 |
| E.1.2 | Term | Schizophrenia schizoaffective |
|
| 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 |
| The primary objective of this study is to evaluate change in weight as a result of switching to ziprasidone, in subjects who have failed to achieve a satisfactory clinical response to quetiapine due to lack of efficacy or poor tolerability. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives of this study are to evaluate the effect on additional safety parameters (glucose and lipid metabolism) and efficacy parameters. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
General Inclusion Criteria
1. Males or females, between 18 and 55 years of age, at the time of consent
2. Be a female who is not of child-bearing potential (i.e. surgically sterile or
postmenopausal for at least one year), or be non-pregnant and be established on an
acceptable method of birth control or be one who abstains from sex. Female subjects
must meet all of the following criteria:
a. Agree to avoid pregnancy during the study and
b. Have a negative serum pregnancy test (β-HCG) at screening and
c. Use one of the birth control methods listed below for the duration of the trial.
Preferred methods of birth control include:
• An oral contraceptive agent, implantable contraceptive (e.g., Norplant) or an
injectable contraceptive (e.g., Depo Provera) for at least one month prior to
entering the study or prior to having sexual relations during the study and will
continue its use throughout the study, or
• An intrauterine device, or
• Partner has had a vasectomy at least 3 months prior to study start
Also Allowed:
• A double-barrier method of a diaphragm with spermicide, plus a latex
condom, or
• Agree to abstain from sex for the duration of the trial.
Note: complete abstinence will be considered on a case-by-case basis, but must first be reviewed and approved by the sponsor.
3. Subjects must be willing and able to comply with study treatments, scheduled visits, and laboratory tests.
4. Prior to participation in any study procedures, subjects must have read and understood the informed consent which is then signed and dated, indicating that they have been informed of all pertinent benefits and risks of study participation and study procedures.
Psychiatric Inclusion Criteria
1. Subjects must have a primary diagnosis of schizophrenia, any subtype (295.xx), or
schizoaffective disorder as defined in DSM-IV-TR™
2. Subjects must have been treated with oral doses of quetiapine, consistent with medical practice, at a minimum of 300 mg per day for at least three months
3. Subjects must have failed to respond to quetiapine due to lack of efficacy or intolerable side effects
4. Subjects must be treated as outpatients at the time of enrollment; however, subjects in day hospitals and supervised living situations will be allowed to participate.
Medical Inclusion Criteria
1. Subjects must have normal vital signs, physical examination, ECG, and laboratory
findings except for minor deviations determined and documented to be clinically
insignificant by the investigator or a sub-investigator who is a medical doctor.
2. Subjects must have a negative urine drug screen for illicit drugs. At the discretion of the investigator, subjects positive for cannabinoids may be admitted upon sponsor approval. |
|
| E.4 | Principal exclusion criteria |
Subjects …
• unable to provide informed consent
• with a history of repeated non-compliance with treatment
• with contraindications according to the local prescribing information of Ziprasidone
• meeting criteria for an active DSM-IV-TR™ Axis I diagnosis (including psychoactive substance abuse or dependence) other than schizophrenia or schizoaffective disorder within 1 year of study entry
• known to have ingested phencyclidine within 60 days of study entry
• treated within any of the following psychotropic medications; any oral antipsychotic drug (other than quetiapine), tricyclic antidepressants, MAOIs, modafinil, pregabalin, topiramate and zonisamide. Patients on any of these medications require at least a 7 day washout period prior to baseline (visit 2, week 0), except MAOIs (that require at least 14 day washout).
• who’ve received depot antipsychotic medication within 30 days of study entry. Subjects that received depot neuroleptic treatment may be included as long as the subject terminated treatment with the depot antipsychotic medication and has been treated with quetiapine for at least 3 months prior to screening.
• judged by the investigator (based on history, mental status exam, or clinical impression) as being at significant risk of self-injurious/suicidal or violent/homicidal behavior. Subjects who develop significant depression, acute suicidal ideation, or who attempt suicide during the study, will be discontinued from the study and provided with treatment (or an appropriate referral) by the investigator.
• with a history of treatment resistance, defined as the presence of severe symptoms despite adequate trials with more than two typical or atypical antipsychotics (other than quetiapine), or subjects who have been treated with clozapine.
• who are receiving quetiapine at a dose of less than 300 mg/day, or any dose for less than 3 months.
• ever discontinued from ziprasidone treatment due to significant adverse event(s).
• Females who are pregnant, breast feeding, or lactating at screening.
• Females of childbearing potential who are unwilling or unable to use adequate contraception to prevent pregnancy during the study.
• having a history of chronic hepatitis
• with a known history of AIDS, or who have previously tested seropositive for HIV antibody or antigen.
• having used, or are schedule to receive, any medications not allowed by Appendix C
• with any medical condition, medication, or dietary habit that may confound the evaluation of the study drug
• with any unstable or untreated medical illness
• who have a medical condition that would interfere with assessments of efficacy or safety, or expose them to an increased risk of significant adverse events, including but not limited to cardiovascular, neurologic, endocrine, hepatic, respiratory, renal, or hematologic disease per investigator judgment.
• with a history of seizures (except febrile seizures of childhood), epilepsy, or a history of a clinically significant abnormal EEG, or if currently being treated for a seizure disorder.
• with thyroid pathology, or any thyroid hormone test abnormality (including but not limited to hypothyroidism or hyperthyroidism), unless the subject has been stabilized on medications for the past 3 months. The entry into the study of subjects who have minor thyroid hormone test abnormalities must first be discussed with the sponsor.
• with a QTc interval >500 msec (Bazett correction) at the screening or baseline visit; or subjects with a known history of prolongation of QTc interval (including congenital long QT syndrome), acute myocardial infarction (within the past 6 months), or uncompensated heart failure.
• with bradycardia, hypokalemia, hypomagnesemia, or concomitant use of other QTc prolonging drugs, or any other circumstance that could contribute to QTc prolongation.
• with a history of mild, moderate, or severe hepatic insufficiency.
• with any clinically significant abnormal laboratory findings. Note: Subjects with a serum potassium or magnesium level below the normal limit at screening will be excluded from participation. Subjects excluded for this reason can be retested once repleted and entered at a later date if their serum potassium or magnesium normalizes. The sponsor must be notified before a retest is performed.
• with a history of allergy or hypersensitivity to antipsychotic compounds, including ziprasidone, or a history of neuroleptic malignant syndrome.
• who have participated in a clinical trial with an investigational drug or device in the past 30 days, or in more than one trial in the past year.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Unless otherwise specified, endpoints are calculated as the change in a parameter between Baseline and Week 16.
The primary endpoint of the study is the change in weight (kg) at Week 16.
Secondary safety endpoints consist of the following:
• Fasting lipid profile (total cholesterol)
• HDL, LDL and Triglycerides
• Hb A1c
• Fasting glucose and insulin
• Waist and hip circumference
• Abnormal Involuntary Movement Scale (AIMS)
• Spontaneously reported adverse events during the study
- Subjects reporting any adverse event during the study
- Subjects reporting a mild, moderate, or severe adverse event during the study
- Subjects discontinuing due to an adverse event during the study
• Subjects who develop clinically significant abnormalities in blood chemistries, hematologies, or ECG parameters during the study
Secondary efficacy endpoints consist of the following:
• Positive and Negative Symptoms of Schizophrenia (PANSS) total score and
positive and negative subscale scores
• Clinical Global Impression, Improvement Scale (CGI-I) change from Clinical Global
Impression, Severity Scale (CGI-S)
• Calgary Depression Scale for Schizophrenia (CDSS)
• Schizophrenia Cognition Rating Scale (SCoRS)
• Global Assessment of Function Scale (GAF)
• Treatment Satisfaction Questionnaire for Medication (TQSM)
|
|
| 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 | 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 | 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| 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.8.3 |
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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| 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
|
End of Trial is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the trial as stated in the regulatory application. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the trial in that Member State.
End of Trial in all participating countries is defined as Last Subject Last Visit.
|
|
| 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 | 5 |
| 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 | 5 |
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