| 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 | 10004939 |
|
| 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 achieve a long-term maintenance indication for bipolar disorder by comparing the time to intervention for a mood episode (TIME) in subjects receiving double-blind ziprasidone plus a mood stabilizer vs. subjects receiving placebo plus a mood stabilizer. |
|
| E.2.2 | Secondary objectives of the trial |
| Evaluate time to discontinuation for any reason and changes in CGI-S, CGI-I, MRS, MADRS and PANSS. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Demographic and General Inclusion Criteria
Subject 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 male or female.
3. Be at least 18 years of age and the age of legal consent.
4. Be a female who is not of child-bearing potential (ie, surgically sterile or postmenopausal for at least one year), or be non-pregnant and using an acceptable method of birth control for at least one month prior to the screening visit or prior to having sexual relations during the study or be one who abstains from sex.
Subject must meet all of the following criteria:
· Agree to avoid pregnancy during the study and
· Have a negative serum pregnancy test (-HCG) at screening and
· Use one of the birth control methods listed below for the duration of
the trial:
• Preferred methods:
1. An oral contraceptive agent, implantable contraceptive (eg, Norplant)
or an injectable contraceptive (eg, 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
2. An intrauterine device, or
3. Partner has had a vasectomy at least 3 months prior to study start
• also allowed:
4. A double-barrier method of a diaphragm with spermicide, plus a latex
condom, or
5. Agree to abstain from sex for the duration of the trial.
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. If possible, identify a caregiver or a responsible person (eg, family member, social worker, caseworker or nurse) considered reliable by the investigator in providing support to the subject to ensure compliance with study treatment, outpatient visits, and protocol procedures, including alerting trial staff to any signs of imminent risk of a mood episode.
Psychiatric inclusion criteria
Subject must:
1. Have a primary diagnosis of Bipolar I Disorder, recent or current episode manic (DSM-IV 296.4x), or mixed (DSM-IV 296.6x), as determined by a structured clinical interview (SCID-P) at screening.
2. Have a recent or current manic or mixed Bipolar I episode that began no more than 90 days prior to the screening visit.
3. Have a documented history (as per source documents) of at least one previous, treated manic or mixed episode of at least moderate severity within the past 2 years.
4. Be on a documented therapeutic level of a mood stabilizer, either lithium (0.6-1.2 mEq/L) or divalproex sodium (50-125 ug/ml), for at least 2 weeks prior to the Baseline visit of the open label period.
5. Have an MRS score ≥14 (with scores of 2 or higher on at least 4 items) if currently receiving the therapeutic level of a lithium or divalproex sodium for at least 2 weeks at the Screening Visit.
6. Have an MRS score of ≥18 (with scores of 2 or higher on at least 4 items), if not currently on lithium or divalproex sodium at the Screening visit, or on a mood stabilizer other than lithium or divalproex sodium. Subjects on a different mood stabilizer must be willing and be appropriate to switch to either lithium or divalproex sodium. Subjects must receive 2 weeks of mood stabilizer exposure in the therapeutic range, and after 2 weeks treatment within that range must have an MRS score ≥14 (with scores of 2 or higher on at least 4 items).
7. Be willing and able to discontinue all psychotropic medications during the trial, except lithium or divalproex sodium and lorazepam or zolpidem tartrate as specified in the protocol (a benzodiazepine similar to lorazepam may be used, if lorazepam is not available or cannot be tolerated).
|
|
| E.4 | Principal exclusion criteria |
Psychiatric exclusion criteria:
Subject must not:
1. Suffer from ultra-fast rapid cycling (defined as 8 or more mood episodes over the previous 12 month period).
2. Be clinically stable on another treatment regimen that is also well tolerated (ie, clinical reason must exist to discontinue current treatment and enter subject into protocol).
3. Be at an imminent risk of harm to self or to others.
4. Have a diagnosis of mental retardation 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 a history of treatment resistance to at least two other antipsychotic medications (after adequate dose and length of treatment).
8. Have a history of treatment resistance or intolerance to ziprasidone (adequate length and dose of treatment).
9. Have received ziprasidone in a previous clinical trial.
10. Have received clozapine within 12 weeks, a depot antipsychotic within 4 weeks or a monoamine oxidase inhibitor within 2 weeks prior to baseline.
11. Have been judged by the investigator to be medically non-compliant in the management of their disease.
Medical exclusion criteria
Subject must not:
1. Have an uncontrolled, unstable clinically significant medical condition (eg, renal, hepatic, endocrine, respiratory, cardiovascular, hematologic, immunologic, cerebrovascular disease, or malignancy), including extreme obesity (body mass index [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 any clinically significant abnormal laboratory, vital sign, physical examination, or ECG finding that, in the opinion of the investigator, precludes trial participation. In addition, subjects must not:
· Have hypokalemia or hypomagnesemia at screening: These subjects may not be entered into the trial until these electrolytes have been repleted and confirmed by laboratory testing to be within normal limits.
· Have severe dehydration or sodium depletion.
· Have SGOT or SGPT ≥2X, alkaline phosphatase ≥1.2X or total bilirubin ≥1.5X times the upper limits of the reference range at the Screening assessment.
· Have a dietary habit (eg, fasting) or illness (eg, bulimia, anorexia nervosa, chronic and severe diarrhea) or require any concomitant medication that may interfere with the absorption of ziprasidone.
· Have a history of chronic hepatitis.
· Have serologic evidence of acute hepatitis or chronic hepatitis (positive HBsAg).
· Have hepatitis C antibodies plus elevated LFT’s.
· 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). Note: 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.
· Have a clinically significant ECG abnormality at Screening or Baseline, a history of cardiac arrhythmias, conduction abnormalities or known history of QT prolongation (including congenital long QT syndrome).
3. Have a positive result on the serum pregnancy test at Screening or Baseline, or the intention to become pregnant or breastfeed during the course of the trial. Because the effects of ziprasidone on the fetus and developing infant are not known, patients who are pregnant or breast-feeding will be excluded from the study.
4. Have known serological evidence of HIV antibody.
5. Have a urine drug screen that is positive for morphine, cocaine, or amphetamines (at the discretion of the investigator and after discussion with the Sponsor or designated representative, subjects with urine drug screen positive for marijuana or benzodiazepines may be eligible for admission, provided the subject does not meet any other exclusion criteria).
6. Have used phencyclidine at any time during the 30-day period preceding Screening.
7. Have a seizure disorder beyond childhood or taking any anticonvulsants to prevent seizures.
8. Have a history of neuroleptic malignant syndrome.
9. Have a history of tardive dyskinesia that did not respond to treatment.
10. Have a known allergy or hypersensitivity to ziprasidone.
11. Have taken another investigational drug within 30 days prior to baseline |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to intervention for a mood episode (TIME) during the Double Blind Maintenance Period based on criteria above. Analysis with Kaplan-Meier survival curves, log rank test. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | Yes |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | 7 |
| 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 | 10 |
Print
