A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study ToEvaluate the Efficacy and Safety of Adjunctive Aripiprazole Therapy in the Treatment of Mania in Bipolar I Disorder Patients Treated with Valproate or Lithium and in Need of Further Clinical Improvement.Revised Protocol 02, Incorporating Administrative Letters 01 and 02 and Amendment 02 (v2.0, dated 17-oct-2008)

Conditions: Bipolar I Mania (manic or mixed episode)
MedDRA version: 9.1Level: LLTClassification code 10026749Term: Mania

Registration Number: EUCTR2007-005959-42-PL

Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 485

Inclusion Criteria

1) Signed Written Informed Consent
a) Subjects must be competent to understand the nature of the study, sign the informed consent, agree to comply with prescribed dosage regimens, discontinuation of prohibited concomitant medication, report for regularly scheduled visits, able to provide reliable information for safety, efficacy and Quality of Life assessments and communicate to the investigator about adverse events and concomitant medication use;
b) The informed consent process must be documented by signing the informed consent form prior to any study-related procedures including alterations in medications in preparation for study entry and subject’s assignment via Interactive Voice Response System (IVRS).
2) Target Population
a) Subjects with Bipolar I Disorder Mania, manic or mixed episode, with or without psychotic features, as defined by DSM-IV-TR and confirmed by the M.I.N.I., presenting with ongoing treatment with lithium or valproate and based on the investigator’s clinical judgment could benefit from adjunctive treatment with aripiprazole.
b) Subjects with therapeutic serum levels of lithium or valproate (as per local SmPC) and a YMRS Total Score of = 16 at screening and baseline and, in case of decrease, a = 35% decrease of YMRS score from the initial screening visit prior to randomization (YMRS to be assessed 14-28 days after blood draw confirming the therapeutic serum level of lithium or valproate).
c) Subjects on lithium or valproate treatment combined with antipsychotic medication other than aripiprazole can be enrolled provided that the other antipsychotic medication is washed out at least 3 days prior to the blood draw for the therapeutic plasma levels of lithium and valproate determination. Long-acting antipsychotics must be washed out prior to entering the double-blind treatment as indicated in Section 5.5 of the protocol. Those subjects who are currently improving or stable on a lithium/valproate and antipsychotic combination treatment and who in Investigator's clinical judgment would not benefit from adjunctive treatment with aripiprazole should not be considered for the trial.
3) Age and Sex
a) Men and women, = 18 years of age
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 4 weeks after
the last dose of investigational product in such a manner that the risk of pregnancy
is minimized. WOCBP must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of
investigational product. Acceptable methods include oral, injectable or implantable contraceptives, intrauterine devices or barrier methods such as condoms, diaphraghms;
b) WOCBP using a prohibited contraceptive method. No specific contraceptive methods are prohibited in this study. Women practicing abstinence should use a reliable method of contraception if they choose to become sexually active during the study;
c) Women who are pregnant or breastfeeding;
d) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
2) Target Disease Exceptions
a) Subjects presenting clinically with a DSM-IV-TR diagnosis of: delirium, dementia, amnestic or other cognitive disorders, or a psychotic disorder (e.g., schizophrenia or schizoaffective disorder).
b) Subjects with a current Axis I (DSM-IV-TR) diagnosis of Bipolar II Disorder, Bipolar Disorder NOS, or any other primary psychiatric disorder other than Bipolar I Disorder Mania.
3) Medical History and Concurrent Diseases
a) Subjects considered treatment refractory by investigator judgment for manic symptoms
b) Subjects previously nonresponsive (by investigator judgment) to aripiprazole for
manic symptoms.
c) Subjects with a significant risk of committing suicide based on history, mental status exam, or investigator’s judgment.
d) Subjects who meet DSM-IV-TR criteria for cocaine dependence or abuse only within the past 3 months prior to screening.
e) Subjects with thyroid pathology (i.e., hypothyroidism or hyperthyroidism) that in
the investigator’s judgment may interfere with safety and efficacy assessments.
f) Subjects with a history of neuroleptic malignant syndrome from antipsychotic agents, or subjects where - according to investigator’s judgment - neuroleptic
malignant syndrome can not be ruled out in the presence of an increased CPK;
g) Subjects who have a history or evidence of a medical condition that would expose
them to an undue risk of a significant adverse event or interfere with assessments
of safety or efficacy during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine (e.g., Addison’s Disease), immune, neurologic, or hematologic disease as determined by the clinical judgment of the investigator;
h) Subjects with a significant history of seizure disorder (e.g., epilepsy);
4) Physical and Laboratory Test Findings
a) The following laboratory test results, vital sign and ECG findings are exclusionary:
? QTc > 475 msec
? Platelets = 75,000/mm³
? Hemoglobin = 9g/dL
? Neutrophils, absolute = 1000/mm³
? Subjects with detectable levels of cocaine in the drug screen.
? AST (SGOT) or ALT (SGPT) > 3x upper limit of normal
? Creatinine = 2 mg/dL [or = 177 µmol/L]
? Diastolic blood pressure > 105 mmHg
If one or more laboratory, vital signs or ECG values are questionable, the test(s) may
be repeated and these eligibility criteria re-evaluated. In addition, subjects should be excluded if they have any other abnormal laboratory test result, vital sign result or ECG finding that in the investigator’s judgment is medically significant, in that it would impact the safety of the subject or the interpretation of the study results.
5) Allergies and Adverse Drug Reactions
a) Subjects who are known to be allergic, intolera