Efficacy of Aripiprazole in Combination with Lithium or Valproate in the Long Term Treatment of Mania in Patients with Bipolar I Disorder Partially Nonresponsive to Lithium or Valproate MonotherapyRevised Protocol 4 incorporating Amendments 2 & 4 & 6 & 7+ Pharmacogenetics Blood Sample Amendment 1, version 1.0 dated 13-Jul-05

Phase 1

• Conditions: Bipolar I Disorder

• Registration Number: EUCTR2005-001233-16-CZ
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-04-12
• Last Update Posted: 5 December 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1100

Inclusion Criteria

1) Patients able to give informed consent, and/or consent obtained from a legally acceptable representative (as required by IRB/IEC) prior to the initiation of any protocol required procedures;
2) Patients meeting DSM-IV-TR criteria for Bipolar I Disorder, currently experiencing a
manic or mixed episode with or without psychotic features, as confirmed by the SCID; Rapid cyclers with <7 mood episodes in the last year will be included;
3) Patients with a Y-MRS total score of = 16 at the Screening Visit;
4) Patients with a history of one or more manic or mixed episodes of sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic;
5) Patients who are able to understand the nature of the study and follow protocol requirements, and who can be reliably rated on assessments scales;
6) Men and women, = 18 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 study. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Postmenopausal is defined as:
• Amenorrhea = 12 consecutive months without another cause or
• For women with irregular menstrual periods and on hormone replacement therapy
(HRT), a documented serum follicle stimulating hormone (FSH) level = 35 mIU/mL.

Inclusion Criteria Assessed during Phase 1:
7) Patients with an adequate washout of prohibited concomitant medications;
8) Patients with lithium or valproate serum level within therapeutic range (lithium: 0.6 -
1.0 mmol/l or valproate: 50 - 125 µg/ml);
9) Patients with a Y-MRS total score of = 16, two weeks after therapeutic levels of
mood stabilizer are achieved, with no more than a 35% decrease from the initial YMRS assessment; an increased or unchanged Y-MRS score is also allowed;

Inclusion Criteria Assessed Prior to Entry into Phase 3:
10) Patients whose bipolar disorder is stable as evidenced by:
a) Y-MRS total score and MADRS total score that has been = 12 for at least 12 weeks, with a maximum of one excursion (defined as a Y-MRS total score > 12 and/or a MADRS total score > 12) in the intervening interval;
b) Y-MRS and a MADRS total score of = 12 at the final Phase 2 Visit.

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) 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 study.
2) WOCBP using a prohibited contraceptive method.
3) Women who are pregnant or breastfeeding.
4) Women with a positive pregnancy test on enrollment or prior to study drug administration.
5) Patients presenting with a current DSM-IV-TR diagnosis of delirium, dementia, amnestic or other cognitive disorders, or a psychotic disorder. Also, patients with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder;
6) Patients with a current Axis I (DSM-IV-TR) diagnosis of bipolar II disorder, rapid cyclers experiencing seven or more mood episodes (manic, depressive, or mixed) within the past year, bipolar disorder NOS, or any other primary psychiatric disorder other than Bipolar I Disorder;
7) Patients experiencing their first manic episode;
8) Patients with a current manic or mixed episode with a duration of > 2 years;
9) Patients considered treatment refractory to treatment for manic symptoms. In addition, patients with a history of unresponsiveness to clozapine must be discussed with the CRO Medical Monitor prior to initiating study medication;
10) Patients with a significant risk of committing suicide;
11) Patients who currently meet DSM-IV-TR criteria for substance abuse or substance
dependence;
12) Patients with thyroid pathology, unless condition has been stabilized with medications for at least the past three months. In addition, patients with thyroid conditions will not be allowed treatment with lithium;
13) Patients 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;
14) Patients with epilepsy or a history of seizures (except for childhood febrile seizures, post traumatic, alcohol withdrawal, etc.);
15) Patients with a CPK = 550 U/L must be approved by the sponsor prior to randomization;
16) Patients with a positive drug screen for cocaine;
17) The following laboratory tests results, vitals signs, and ECG findings are
exclusionary:
a) Platelets = 75,000/mm3
b) Hemoglobin = 9g/dL
c) Neutrophils, Absolute = 1000/ mm3
d) SGOT (AST) > 3x Upper Limit of Normal
e) SGPT (ALT) > 3x Upper Limit of Normal
f) Creatinine = 2 mg/dL
g) Patients may be retested during the screening period (Phase 1) at the investigator’s discretion. Upon retest, if results do not meet the exclusion criteria listed above, the patient may continue onto Phase 2;
h) Diastolic blood pressure > 105 mmHg
i) QTc > 475 msec
In addition, patients 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 patient or the interpretation of the study results (see Protocol Appendices 3, 4, and 5);
18) Patients who are known to be allergic, intolerant, or unresponsive to previous aripiprazole treatment;
19) Hypersensitivity to antipsychotic agents;
20) Patients allergic, intolerant, hypersensitive or refractory to both lithium and valproate;
21) Patients with a history of neuroleptic malignant syndrome from antipsychotic agents;
22) Patients likely to require prohibited concomitant therapy, (see Protocol Section 6.4);
23) Patients who have participated in a clinical trial with an investigation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified