A Phase 3, randomized, 6-month, double blind trial in subjects with Bipolar I Disorder to evaluate the continued safety and maintenance of effect of Ziprasidone plus a mood stabilizer (vs placebo plus a mood stabilizer) following a minimum of 4 months of response to open-label treatment with both agents.
- Conditions
- Bipolar I DisorderMedDRA version: 8.0Level: LLTClassification code 10004939
- Registration Number
- EUCTR2005-004167-27-ES
- Lead Sponsor
- Pfizer, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 512
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 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:
a. 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 and will continue its use throughout the study,
or
b. A barrier method of contraception, eg an intrauterine device or
diaphragm with spermicide, plus a condom while participating in the study,
or
c. 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.Have a caregiver or an identified 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 ³14 (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 ³18 (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 ³14 (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 sod
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 TRTM 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 clin
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To achieve a long-term maintenance indication for bipolar disorder by comparing the time to intervention for a mood episode (TIME) in subjects receiving ziprasidone plus a mood stabilizer vs. subjects receiving placebo plus a mood stabilizer following prior stabilization of symptoms with 4-6 months of adjunctive treatment with ziprasidone plus a mood stabilizer.;Secondary Objective: Evaluate time to discontinuation for any reason and changes in CGI-S, CGI-I, MRS, MADRS and PANSS.;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.
- Secondary Outcome Measures
Name Time Method