Trial Outcomes & Findings for A Multicenter, Placebo-controlled, Double-blind Investigative Extension Trial of the Safety and Efficacy of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode (NCT NCT00606177)
NCT ID: NCT00606177
Last Updated: 2014-02-12
Results Overview
Using LOCF datasets, descriptive statistics of actual values for changes of YMRS total scores from baseline (Day 1 of preceding study) to endpoint (Day 154) was calculated for each treatment group. YMRS is composed of 11 evaluation items with 5 rating levels each. Items rated on a scale of 0 to 4 (comprising 5 rating levels of one point each) are 1) levated mood, 2) increased motor activity/energy, 3) sexual interest, 4) sleep, 7) language-thought disorder, 10) appearance, and 11) insight. Items rated on a scale of 0 to 8 (comprising 5 rating levels of two points each) are 5) irritability, 6) speech (rate and amount), 8) content, and 9) disruptive-aggressive behavior. YMRS ranges from 0 (best possible outcome) to 60 (worst possible outcome).
COMPLETED
PHASE3
99 participants
Baseline (Day 1 of preceding study) , Day 154 or at discontinuation
2014-02-12
Participant Flow
Participant milestones
| Measure |
Aripiprazole
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
|---|---|---|
|
Overall Study
STARTED
|
55
|
44
|
|
Overall Study
COMPLETED
|
28
|
19
|
|
Overall Study
NOT COMPLETED
|
27
|
25
|
Reasons for withdrawal
| Measure |
Aripiprazole
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
9
|
5
|
|
Overall Study
Lack of Efficacy
|
3
|
7
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
4
|
|
Overall Study
Withdrawal by Subject
|
5
|
6
|
|
Overall Study
Progression to depressive phase
|
6
|
1
|
|
Overall Study
Diabetic blood glucose level/ High HbA1c
|
1
|
1
|
|
Overall Study
Change of residence or other commitments
|
1
|
1
|
Baseline Characteristics
A Multicenter, Placebo-controlled, Double-blind Investigative Extension Trial of the Safety and Efficacy of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode
Baseline characteristics by cohort
| Measure |
Aripiprazole
n=54 Participants
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
n=42 Participants
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
Total
n=96 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.7 years
STANDARD_DEVIATION 11.95 • n=5 Participants
|
37.8 years
STANDARD_DEVIATION 11.67 • n=7 Participants
|
38.3 years
STANDARD_DEVIATION 11.78 • n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
54 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
4 participants
n=5 Participants
|
9 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
China
|
9 participants
n=5 Participants
|
9 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
22 participants
n=5 Participants
|
10 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Malaysia
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Indonesia
|
5 participants
n=5 Participants
|
2 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Philippines
|
10 participants
n=5 Participants
|
6 participants
n=7 Participants
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1 of preceding study) , Day 154 or at discontinuationPopulation: FAS: The FAS consisted of subjects who had received at least one dose of investigational product and for whom the post-dosing efficacy parameter data had been obtained. Cases of GCP violation were excluded from analysis.
Using LOCF datasets, descriptive statistics of actual values for changes of YMRS total scores from baseline (Day 1 of preceding study) to endpoint (Day 154) was calculated for each treatment group. YMRS is composed of 11 evaluation items with 5 rating levels each. Items rated on a scale of 0 to 4 (comprising 5 rating levels of one point each) are 1) levated mood, 2) increased motor activity/energy, 3) sexual interest, 4) sleep, 7) language-thought disorder, 10) appearance, and 11) insight. Items rated on a scale of 0 to 8 (comprising 5 rating levels of two points each) are 5) irritability, 6) speech (rate and amount), 8) content, and 9) disruptive-aggressive behavior. YMRS ranges from 0 (best possible outcome) to 60 (worst possible outcome).
Outcome measures
| Measure |
Aripiprazole
n=54 Participants
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
n=42 Participants
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
|---|---|---|
|
Young Mania Rating Scale (YMRS)
|
-22.6 scores on a scale
Standard Deviation 11.08
|
-15.4 scores on a scale
Standard Deviation 12.90
|
SECONDARY outcome
Timeframe: Baseline (Day 1 of preceding study), Day 154 or at discontinuationPopulation: FAS: The FAS consisted of subjects who had received at least one dose of investigational product and for whom the post-dosing efficacy parameter data had been obtained. Cases of GCP violation were excluded from analysis.
Using LOCF datasets, descriptive statistics of actual values for change of CGI-BP severity of illness score (mania) from baseline (Day 1 of preceding study) to endpoint (Day 154) were calculated for each treatment group. CGI-BP severity of illness is a scale for overall evaluation of the severity of bipolar disorder; it comprises 3 components-mania, depression, and overall bipolar illness. CGI-BP severity of illness score (mania) ranges form 1 (normal, not ill) to 7 (very severely ill).
Outcome measures
| Measure |
Aripiprazole
n=54 Participants
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
n=42 Participants
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
|---|---|---|
|
Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness (Mania)
|
-2.9 scores on scale
Standard Deviation 1.45
|
-1.9 scores on scale
Standard Deviation 1.70
|
Adverse Events
Aripiprazole
Placebo
Serious adverse events
| Measure |
Aripiprazole
n=54 participants at risk
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
n=42 participants at risk
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Clavicle Fracture
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
0.00%
0/42 • 22 weeks
|
|
Nervous system disorders
Akathisia
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
0.00%
0/42 • 22 weeks
|
|
Nervous system disorders
Stupor
|
0.00%
0/54 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Psychiatric disorders
Depression
|
3.7%
2/54 • Number of events 2 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Psychiatric disorders
Bipolar I Disorder
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Psychiatric disorders
Mania
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Psychiatric disorders
Bipolar Disorder
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
0.00%
0/42 • 22 weeks
|
|
Psychiatric disorders
Delusion of Grandeur
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
0.00%
0/42 • 22 weeks
|
Other adverse events
| Measure |
Aripiprazole
n=54 participants at risk
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered 24 ,12, or 30 mg/day of aripiprazole once daily for 154 days.
|
Placebo
n=42 participants at risk
Patients who had completed the preceding study and demonstrated drug efficacy were the target.
Subjects were administered placebo once daily for 154 days.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
11.1%
6/54 • Number of events 6 • 22 weeks
|
7.1%
3/42 • Number of events 4 • 22 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
7.4%
4/54 • Number of events 5 • 22 weeks
|
9.5%
4/42 • Number of events 6 • 22 weeks
|
|
Gastrointestinal disorders
Salivary Hypersecretion
|
11.1%
6/54 • Number of events 7 • 22 weeks
|
4.8%
2/42 • Number of events 2 • 22 weeks
|
|
Gastrointestinal disorders
Vomiting
|
3.7%
2/54 • Number of events 2 • 22 weeks
|
9.5%
4/42 • Number of events 5 • 22 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/54 • 22 weeks
|
14.3%
6/42 • Number of events 11 • 22 weeks
|
|
Gastrointestinal disorders
Toothache
|
5.6%
3/54 • Number of events 5 • 22 weeks
|
4.8%
2/42 • Number of events 3 • 22 weeks
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
7.1%
3/42 • Number of events 3 • 22 weeks
|
|
Hepatobiliary disorders
Hepatic Function Abnormal
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
7.1%
3/42 • Number of events 3 • 22 weeks
|
|
Infections and infestations
Nasopharyngitis
|
9.3%
5/54 • Number of events 6 • 22 weeks
|
11.9%
5/42 • Number of events 6 • 22 weeks
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
5.6%
3/54 • Number of events 4 • 22 weeks
|
11.9%
5/42 • Number of events 5 • 22 weeks
|
|
Injury, poisoning and procedural complications
Excoriation
|
5.6%
3/54 • Number of events 4 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Investigations
Weight Increased
|
16.7%
9/54 • Number of events 9 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
5.6%
3/54 • Number of events 3 • 22 weeks
|
0.00%
0/42 • 22 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle Rigidity
|
7.4%
4/54 • Number of events 5 • 22 weeks
|
4.8%
2/42 • Number of events 2 • 22 weeks
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
7.1%
3/42 • Number of events 4 • 22 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
7.1%
3/42 • Number of events 3 • 22 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
5.6%
3/54 • Number of events 4 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Nervous system disorders
Akathisia
|
31.5%
17/54 • Number of events 20 • 22 weeks
|
16.7%
7/42 • Number of events 8 • 22 weeks
|
|
Nervous system disorders
Tremor
|
18.5%
10/54 • Number of events 11 • 22 weeks
|
9.5%
4/42 • Number of events 7 • 22 weeks
|
|
Nervous system disorders
Headache
|
3.7%
2/54 • Number of events 2 • 22 weeks
|
11.9%
5/42 • Number of events 6 • 22 weeks
|
|
Nervous system disorders
Dizziness
|
3.7%
2/54 • Number of events 2 • 22 weeks
|
9.5%
4/42 • Number of events 6 • 22 weeks
|
|
Nervous system disorders
Bradykinesia
|
9.3%
5/54 • Number of events 6 • 22 weeks
|
0.00%
0/42 • 22 weeks
|
|
Nervous system disorders
Dyskinesia
|
5.6%
3/54 • Number of events 4 • 22 weeks
|
2.4%
1/42 • Number of events 1 • 22 weeks
|
|
Nervous system disorders
Somnolence
|
5.6%
3/54 • Number of events 4 • 22 weeks
|
2.4%
1/42 • Number of events 2 • 22 weeks
|
|
Psychiatric disorders
Insomnia
|
13.0%
7/54 • Number of events 7 • 22 weeks
|
16.7%
7/42 • Number of events 13 • 22 weeks
|
|
Psychiatric disorders
Mania
|
1.9%
1/54 • Number of events 1 • 22 weeks
|
7.1%
3/42 • Number of events 3 • 22 weeks
|
Additional Information
Director of Clinical Research and Development
Otsuka Pharmaceutical Co., Ltd.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place