E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10004939 |
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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 aim of this study is to compare the efficacy and tolerability of ziprasidone versus olanzapine in the treatment of acute mania. |
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E.2.2 | Secondary objectives of the trial |
An open label extension study will further evaluate the efficacy, safety, and tolerability of ziprasidone compared with olanzapine over a period of 6 months in patient responding to acute treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Demographic and General Inclusion Criteria Subjects must: 1.Personally sign the written informed consent after the scope and nature of the investigation has been explained to them before any study-specific procedure/evaluation is initiated or performed. 2. Be either male or female. 3. Be at least 18 years of age and at the age of legal consent, and no older than 65 years of age. 4. If female be not of child-bearing potential (i.e. surgically sterile or postmenopausal for at least one year), or be non-pregnant and using an acceptable method of birth control (such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner) for at least one month prior to the screening visit if necessary, and for the duration of the study period. 5. Be likely to comply with the protocol and medication regimen. 6. Be fluent in the language of the investigator and study staff (including raters). 7. Be either an in- or out-patient.
Psychiatric Inclusion Criteria 1. Have a primary diagnosis of Bipolar I Disorder, current episode manic (DSM-IV 296.4x) or mixed (DSM-IV296.6x) as determined by the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-P) at screening. 2. A minimum score of 20 on the YMRS at the randomisation visit.
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E.4 | Principal exclusion criteria |
Psychiatric 1. A primary diagnosis other than Bipolar I Disorder. 2. Patients diagnosed with rapid cycling of Bipolar I Disorder. 3. Patients who are an imminent risk of self harm or harm to others. 4. Have a diagnosis of learning disability or organic brain syndrome. 5. Have a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse. 6. Have a current (within 2 months prior to screening) DSM-IV-TR defined substance abuse/dependence (excluding nicotine and caffeine). 7. Have used phencyclidine at any time during the 30-day period preceding screening. 8. Participation in a clinical trial within 1 month before study entry. 9. Have received clozapine within 4 weeks, a depot antipsychotic within 4 weeks or a monoamine oxidase inhibitor within 2 weeks prior to baseline. 10. Have been judged by the investigator to be medically non-compliant in the management of their disease. 11. Patients currently treated with olanzapine or ziprasidone at study start. 12. Ziprasidone or olanzapine treatment had been withdrawn because of clinically important and/or intolerable adverse events or who exhibited a lack of treatment response when these drugs had been given at therapeutic doses and there was good compliance from the patient. 13. Documented history of intolerance to olanzapine or ziprasidone.
Medical exclusion criteria Subjects must not: 1. Have an uncontrolled, unstable clinically significant medical condition (e.g. renal, hepatic, endocrine, respiratory, cardiovascular, heamatologic, immunologic, cerebrovascular disease, or malignancy), including diabetic subjects taking insulin, extreme obesity (BMI >35 kg/m2) or anorexia (BMI <18.5 kg/m2), which, in the opinion of the investigator, may interfere with the interpretation of safety or efficacy evaluations. 2. Have hypokalemia or hypomagnesaemia at screening: These subjects may not be entered into the trial until these electrolytes have been repleted and the laboratory values for potassium and magnesium are within normal limits. 3. Have severe dehydration or sodium depletion. These subjects may not be entered into the trial until these electrolytes have been repleted and the laboratory values for sodium are within normal limits. 4. Have ALT or AST ≥2X, alkaline phosphatase ≥ 1.2X or total bilirubin ≥ 1.5X times the upper limits of the reference range at the Screening assessment. 5. Have serologic evidence of acute hepatitis or chronic hepatitis (positive HBsAg). Subjects with known hepatitis C antibodies and elevated liver function enzymes will be excluded from study participation. 6. Have a history of significant cardiovascular disease or significant concurrent cardiovascular disease, including uncontrolled hypertension (sitting diastolic pressure >95 mm Hg and/or sitting systolic pressure > 170 mm Hg with or without treatment), hypotension, congestive heart failure, angina pectoris, bypass surgery, history of myocardial infarction or ischemic heart disease, uncompensated heart failure or recent acute myocardial infarction (within the past 6 months). · Controlled essential hypertension (stable for at least 2 months by diet and/or pharmacotherapy) and non-clinically significant sinus bradycardia and sinus tachycardia will not be considered significant medical illnesses and will not exclude a subject from the study. 7. Have a clinically significant ECG abnormality at Screening, a history of cardiac arrhythmias, conduction abnormalities or known history of QT prolongation (including congenital long QT syndrome) or QTc ≥ 500 msec at screening or baseline. 8. Have a positive result on the urine pregnancy test at screening, or the intention to become pregnant or breastfeed during the course of the trial. Because the effects of ziprasidone on the foetus and developing infant are not known, patients who are pregnant or breast-feeding will be excluded from the study. 9. Have known serological evidence of HIV antibodies. 10. Have a seizure disorder beyond childhood or taking any anticonvulsants to prevent seizures. 11. Have a history of neuroleptic malignant syndrome. 12. Have a history of tardive dyskinesia that did not respond to treatment. 13. Have taken another investigational drug within 30 days prior to baseline.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the mean reduction, after 4 weeks of treatment, in the YMRS score during the double blind phase. |
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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 | Yes |
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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 50 |
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 |
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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
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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 | 8 |
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 | 8 |