Bipolar DisorderPhase 4NCT00261443
A Study of Aripiprazole (Abilify) in Patients With Bipolar Mania
A Phase 4 study testing Lithium or Valproate with Aripiprazole in people with Bipolar Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 83 sites in 9 countries.
Trial summary
The purpose of this clinical research study is to learn if outpatients with bipolar mania who are partially nonresponsive to lithium or valproate monotherapy can achieve stable symptoms on a combination treatment of aripiprazole plus lithium or valproate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Lithium or Valproate with Aripiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,270 participants
- Where
- 83 sitesin 9 countries
- Study dates
- Sep 2005to Oct 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women > or = to 18 years of age meeting Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder, currently experiencing a manic or mixed episode with a history of one or more manic or mixed episodes or sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic.
Who cannot join
None listed.
Trial locations and contacts
83 sites in 9 countries.
83 sites in 9 countries
United States29 sites
Pravin Kansagra, M.D.
Anaheim, California, 92801
Senior Adults Specialty Research, Inc.
Austin, Texas, 78757
Rakesh Ranjan, Md & Associates, Inc.
Beachwood, Ohio, 44122
Northwest Clinical Research Center
Bellevue, Washington, 98004
Psychopharmacology Research Network Of Torrance
Cerritos, California, 90703
University Of Cincinnati Medical Center
Cincinnati, Ohio, 45267
Cns Research Institute, P.C.
Clementon, New Jersey, 08021
Metro Health Medical Center
Cleveland, Ohio, 44109
Atp Clinical Research, Inc.
Costa Mesa, California, 92626
Us Clinical Research Centers, Llc
Costa Mesa, California, 92627
Futuresearch Trials
Dallas, Texas, 75231
Midwest Clinical Research Center
Dayton, Ohio, 45408
Insite Clinical Research
DeSoto, Texas, 75115
Red Oak Psychiatry Associates, Pa
Houston, Texas, 77090
Va Long Beach Healthcare System
Long Beach, California, 90822
Synergy Clinical Research Center
National City, California, 91950
Neuropsychiatric Research Associates
New York, New York, 10128
University Of California, Irvine Medical Center
Orange, California, 92868
Clinical Neuroscience Solutions, Inc.
Orlando, Florida, 32806
Portland Va Medical Center
Portland, Oregon, 97201
Psychiatry And Clinical Research
Raleigh, North Carolina, 27609
University Of Utah School Of Medicine
Salt Lake City, Utah, 84132
Carman Research
Smyrna, Georgia, 30080
Psych Care Consultants Research
St Louis, Missouri, 63128
Behavioral Medical Research Of Staten Island
Staten Island, New York, 10305
Richmond Behavioral Associates
Staten Island, New York, 10312
University Of South Florida
Tampa, Florida, 33613
Tuscaloosa Va Medical Center
Tuscaloosa, Alabama, 35404
University Of Massachusetts Medical School
Worcester, Massachusetts, 01605
India14 sites
Local Institution
Ahmedabad, Gujarat, 380 006
Local Institution
Ahmedabad, Gujarat, 6577647
Local Institution
Delhi, 110 092
Local Institution
Hyderabad, Andhra Pradesh, 500 034
Local Institution
Hyderabad, 500 038
Local Institution
Kalyan (West), Maharashtra, 421 301
Local Institution
Mangalore, Manipal, 576 104
Local Institution
Mumbai, Sion (W), 400 022
Local Institution
Mumbai, 400 008
Local Institution
Mumbai, 400 058
Local Institution
Nāgūr, Maharashtra, 440010
Local Institution
New Delhi, 110 002
Local Institution
New Delhi, 110 065
Local Institution
Pune, Maharashtra, 400 001
France9 sites
Local Institution
Dole, 39100
Local Institution
Hénin-Beaumont, 62251
Local Institution
Jonzac, 175003
Local Institution
La Seyne-sur-Mer, 83500
Local Institution
Marseille, 13009
Local Institution
Nantes, Cedex 01, 44035
Local Institution
Nantes, 44000
Local Institution
Nîmes, 30900
Local Institution
Rennes, 35000
Czechia7 sites
Local Institution
Brno, 610 00
Local Institution
Brno, 625 00
Local Institution
Havířov, 736 01
Local Institution
Litoměřice, 412 01
Local Institution
Prague, 120 00
Local Institution
Prague, 160 00
Local Institution
Přerov, 75002
Russia7 sites
Local Institution
Izhevsk, 426053
Local Institution
Moscow, 107258
Local Institution
Nizhny Novgorod, 603107
Local Institution
Saint Petersburg, 190000
Local Institution
Saint Petersburg, 191119
Local Institution
Saratov, 410028
Local Institution
Tomsk, 634014
Brazil6 sites
Local Institution
Aparecida de Goinia, Goiás, 74922
Local Institution
Pelotas, Rio Grande do Sul, 96030 003
Local Institution
Rio de Janeiro, 21020
Local Institution
Salvador, Estado de Bahia, 40325
Local Institution
São Paulo, 02340
Local Institution
São Paulo, 05403
South Africa5 sites
Local Institution
Berea, KwaZulu-Natal, 4001
Local Institution
Cape Town, Western Cape, 7708
Local Institution
Durban, KwaZulu-Natal, 4001
Local Institution
Paarl, Western Cape, 7646
Local Institution
Pretoria, Gauteng, 0001
Croatia4 sites
Local Institution
Rijeka, 51-000
Local Institution
Split, 21000
Local Institution
Zadar, 23000
Local Institution
Zagreb, 10 090
About this study
Official title: Efficacy of Aripiprazole in Combination With Lithium or Valproate in the Long-Term Maintenance Treatment of Bipolar I Disorder in Outpatients Partially Nonresponsive to Lithium or Valproate Monotherapy
The purpose of this clinical research study is to learn if outpatients with bipolar mania who are partially nonresponsive to lithium or valproate monotherapy can achieve stable symptoms on a combination treatment of aripiprazole plus lithium or valproate.
- Conditions
- Bipolar Disorder
- Being tested
- Lithium or Valproate with placebo (PBO), Lithium or Valproate with Aripiprazole
- Keywords
- Bipolar I Disorder with a recent manic or mixed episode
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium or Valproate with placebo (PBO)Drug
Tablets, Oral, once daily
lithium 250-2100 mg/day
valproate 250-2500mg/day
Placebo once daily
Lithium or Valproate with AripiprazoleDrug
Also called Abilify, BMS-337039
Tablets, Oral, once daily, 52 weeks post randomization (Pre-Randomization Phases 13-24 weeks)
lithium 250-2100 mg/day
valproate 250-2500mg/day
aripiprazole 15-30 mg/day
| Study group | Role | What they receive |
|---|---|---|
| A1 | Placebo comparator | /Active Comparator Receives: Drug: Lithium or Valproate with placebo (PBO) |
| A2 | Experimental | Not described Receives: Drug: Lithium or Valproate with Aripiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: hospitalization for a manic, mixed or depressive episode; serious adverse event of worsening disease under study accompanied by a Y-MRS > 16 and/or a MADRS > 16; discontinuation due to lack of efficacy as determined by the investigator accompanied by a Y-MRS > 16 and/or a MADRS > 16.
Measured: Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Secondary outcomes (123)
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline (end of Phase 2), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: relapse is defined as any of the following events accompanied by a Young-Mania Rating Scale (Y-MRS) >16 and/or a Montgomery Åsberg Depression Rating Scale (MADRS) >16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score >16.
Measured: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Kaplan Meier estimated survival rate. Relapse is defined as any of the following events accompanied by a YMRS > 16 and/or a MADRS > 16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score > 16.
Measured: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
The Y-MRS consists of 11 items: 1) Elevated Mood, 2) Increased Motor Activity -Energy, 3) Sexual Interest, 4) Sleep, 5) Irritability, 6) Speech (Rate and Amount), 7) Language -Thought Disorder, 8) Content, 9) Disruptive-Aggressive Behavior, 10) Appearance, 11) Insight. Seven items are rated on a 0 to 4 scale, while 4 items (items 5, 6, 8 and 9) are rated on a 0 to 8 scale (twice the weight of the other items.) For all items, 0 is the "best" rating and 4 or 8 is the "worst" rating. Total Score is the sum of the ratings for all 11 items. The possible Total Scores are from 0 (best) to 60 (worst).
Measured: Baseline (end of ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, + Confirmation of Partial Nonresponse Phase)
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
The Y-MRS consists of 11 items: 1) Elevated Mood, 2) Increased Motor Activity -Energy, 3) Sexual Interest, 4) Sleep, 5) Irritability, 6) Speech (Rate and Amount), 7) Language -Thought Disorder, 8) Content, 9) Disruptive-Aggressive Behavior, 10) Appearance, 11) Insight. 7 items are rated on a 0 to 4 scale, while 4 items (items 5, 6, 8 and 9) are rated on a 0 to 8 scale (twice the weight of the other items.) For all items, 0 is the "best" rating and 4 or 8 is the "worst" rating. Total Score is the sum of the ratings for all 11 items. The possible Total Scores are from 0 (best) to 60 (worst).
Measured: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Measured: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Measured: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall change from preceding phase items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
Measured: Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
Measured: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
Measured: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Number of Participants Maintaining Remission During Phase 3
Remission is defined as Y-MRS Total Score <=12 and MADRS Total Score <=12.
Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Proportion of Participants Discontinuing For Any Reason Through Week 52 (During Phase 3)
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Measured: During Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
Measured: During Phase 2. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate <100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.
Measured: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.
Measured: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
ULN=upper limit of normal; HDL=high density lipoprotein; LDL=low density lipoprotein. Values for ULN are provided by the lab in the database and could be different for each individual patient based on characteristics such as age, gender, or other patient attributes.
Measured: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
Measured: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Measured: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Measured: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
Measured: Baseline
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2
Measured: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Measured: Baseline
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
Measured: Baseline
Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)
Measured: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Hemoglobin
Measured: Baseline
Median Change From Baseline in Hemoglobin
Measured: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Hematocrit
Measured: Baseline
Median Change From Baseline in Hematocrit
Measured: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
Measured: Baseline
Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
Measured: Baseline
Median Change From Baseline in Homeostasis Model Assessment 2(HOMA2)-Percent Beta at Phase 2 Endpoint
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
Measured: Baseline (end of Ph 1), Phase 2 Endpoint (endpoint of a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Change From Baseline in HOMA2 Model Assesses Insulin Resistance (HOMA2-IR) at Phase 2 Endpoint
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
Measured: Baseline (end of Ph 1), Phase 2 Endpoint (endpoint of a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline Platelet Count
Measured: Baseline
Median Change From Baseline in Platelet Count at Phase 2 Endpoint
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Prolactin
Measured: Baseline
Median Change From Baseline in Prolactin at Phase 2 Endpoint
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Leukocytes
Measured: Baseline
Median Change From Baseline in Leukocytes at Phase 2 Endpoint
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline Abnormal Involuntary Movement Scale (AIMS)
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Measured: Baseline
Unadjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) at Phase 2 Endpoint
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline in Simpson-Angus Scale (SAS) Total Score
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50.(lower score=less severe). Negative change scores indicate improvement.
Measured: Baseline
Unadjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score at Phase 2 Endpoint
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower score=less severe). Negative change scores indicate improvement.
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline in Barnes Akathisia Global Clinical Assessment
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Measured: Baseline
Unadjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Phase 2 Endpoint
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Measured: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
Measured: Baseline, During Phase 3 (for highest/lowest values), Week 52
Baseline and Adjusted Mean Change From Baseline in Weight
Measured: Baseline, Weeks 12, 24, 36, 52, During Phase 3 (for highest value)
Number of Participants Showing Relevant Weight Gain During Phase 3
Relevant weight gain: >=7% increase from baseline
Measured: Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment)
Number of Participants Showing Relevant Weight Loss During Phase 3
Relevant weight loss: >=7% decrease from baseline
Measured: Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment)
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Measured: Baseline, Week 12, Week 24, Week 36, Week 52, Week 52 (LOCF), During Phase 3 (for lowest/highest values)
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
ULN=upper limit of normal; Hb=hemoglobin
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample
The change values reported are the median of (post baseline percentage (of white blood cell count) minus baseline percentage (of white blood cell count).
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value)
Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value)
Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value
Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value)
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate <100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower scores=less severe). Negative change scores indicate improvement.
Measured: Baseline, Weeks 4,8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)
Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
Measured: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Measured: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 8 Score range from 0 to 4. A negative score signifies improvement.
Measured: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 9 Score range from 0 to 4. A negative score signifies improvement.
Measured: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 10 Score range from 0 to 4. A negative score signifies improvement.
Measured: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Measured: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
Measured: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72 of LTE Phase. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Mean Change From Baseline in CGI-BP (Mania) Severity of Illness at Extension Phase Endpoint
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Depression) at Extension Phase Endpoint
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Overall) at Extension Phase Endpoint
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Measured: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Measured: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Metabolic abnormalities considered by the investigator as clinically relevant. (Need normal values for each.)
Measured: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Vital sign abnormalities considered by the investigator as clinically relevant.
Measured: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Adverse Events (AEs), by Maximum Intensity
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
Measured: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
Chemistry, hematology, and urinalysis abnormalities considered by the investigator as clinically relevant. Hematocrit: ≤37%(M)/≤32%(F)+3 percentage pts↓from baseline.
Measured: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
ECG abnormalities considered by the investigator as clinically relevant.Left Bundle Branch Block: Not present at Baseline--> present post-baseline.
Measured: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2005 (estimated)
- Study startSep 2005
- Primary completionJun 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,270 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00261443
- Sponsor's protocol ID
- CN138-189
- Status last verified
- Mar 2023
- First submitted
- 1 Dec 2005
- Last updated
- 18 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Marcus R, Khan A, Rollin L, Morris B, Timko K, Carson W, Sanchez R. Efficacy of aripiprazole adjunctive to lithium or valproate in the long-term treatment of patients with bipolar I disorder with an inadequate response to lithium or valproate monotherapy: a multicenter, double-blind, randomized study. Bipolar Disord. 2011 Mar;13(2):133-44. doi: 10.1111/j.1399-5618.2011.00898.x.
PubMed 21443567
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Aripiprazole in Combination With Lithium or Valproate in the Long-Term Maintenance Treatment of Bipolar I Disorder in Outpatients Partially Nonresponsive to Lithium or Valproate Monotherapy
- ClinicalTrials.gov ID
- NCT00261443
- Acronym / sponsor ID
- CN138-189
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar I Disorder with a recent manic or mixed episode
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,270 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 5 Dec 2005 (estimated)
- Results
- Posted 27 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical research study is to learn if outpatients with bipolar mania who are partially nonresponsive to lithium or valproate monotherapy can achieve stable symptoms on a combination treatment of aripiprazole plus lithium or valproate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A1 | Placebo comparator | Drug: Lithium or Valproate with placebo (PBO)/Active Comparator |
| A2 | Experimental | Drug: Lithium or Valproate with Aripiprazole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Men and women > or = to 18 years of age meeting Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder, currently experiencing a manic or mixed episode with a history of one or more manic or mixed episodes or sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium or Valproate with placebo (PBO)Tablets, Oral, once daily lithium 250-2100 mg/day valproate 250-2500mg/day Placebo once daily | Drug | A1 |
| Lithium or Valproate with AripiprazoleAlso: Abilify, BMS-337039Tablets, Oral, once daily, 52 weeks post randomization (Pre-Randomization Phases 13-24 weeks) lithium 250-2100 mg/day valproate 250-2500mg/day aripiprazole 15-30 mg/day | Drug | A2 |
Primary outcome
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Time frame: Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: hospitalization for a manic, mixed or depressive episode; serious adverse event of worsening disease under study accompanied by a Y-MRS > 16 and/or a MADRS > 16; discontinuation due to lack of efficacy as determined by the investigator accompanied by a Y-MRS > 16 and/or a MADRS > 16.
123 secondary outcomes
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Time frame: Baseline (end of Phase 2), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Time frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Time frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Time frame: Baseline (end of ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, + Confirmation of Partial Nonresponse Phase)
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Time frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Time frame: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Time frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Time frame: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Time frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Time frame: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Time frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Time frame: Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Time frame: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Time frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Time frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Number of Participants Maintaining Remission During Phase 3
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Proportion of Participants Discontinuing For Any Reason Through Week 52 (During Phase 3)
Time frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Time frame: During Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
Time frame: During Phase 2. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Time frame: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Time frame: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Time frame: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
Time frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Time frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Time frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint
Time frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint
Time frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
Time frame: Baseline
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
Time frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2
Time frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Time frame: Baseline
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Time frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
Time frame: Baseline
Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)
Time frame: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Hemoglobin
Time frame: Baseline
Median Change From Baseline in Hemoglobin
Time frame: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)
Median Baseline Hematocrit
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21443567Marcus R, Khan A, Rollin L, Morris B, Timko K, Carson W, Sanchez R. Efficacy of aripiprazole adjunctive to lithium or valproate in the long-term treatment of patients with bipolar I disorder with an inadequate response to lithium or valproate monotherapy: a multicenter, double-blind, randomized study. Bipolar Disord. 2011 Mar;13(2):133-44. doi: 10.1111/j.1399-5618.2011.00898.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
83 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lithium or Valproate with Aripiprazole in people with Bipolar Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 83 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 83 sites in United States, India, France, Czechia, Russia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3 (time frame: Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00261443, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.