Trial Outcomes & Findings for A Multicenter, Investigative Study of the Safety and Efficacy of Extended Administration of Aripiprazole in Combination With Mood Stabilizer for the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode (NCT NCT00606320)

Last Updated: 2014-02-12

Results Overview

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). 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

59 participants

Primary outcome timeframe

baseline (Day 1 of preceding study), Day 154 or at discontinuation

Results posted on

2014-02-12

Participant Flow

Participant milestones

Participant milestones
Measure	Aripiprazple Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target. Subjects were administered 24, 12, or 30mg/day of aripiprazole once daily for 154 days in an unblinded manner. Subjects were also administered mood stabilizer concomitantly for 154 days.
Overall Study STARTED	59
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Aripiprazple Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target. Subjects were administered 24, 12, or 30mg/day of aripiprazole once daily for 154 days in an unblinded manner. Subjects were also administered mood stabilizer concomitantly for 154 days.
Overall Study Adverse Event	3
Overall Study Lack of Efficacy	5
Overall Study Physician Decision	7
Overall Study Protocol Violation	8
Overall Study Withdrawal by Subject	10
Overall Study Progression to depressive phase	4

Baseline Characteristics

A Multicenter, Investigative Study of the Safety and Efficacy of Extended Administration of Aripiprazole in Combination With Mood Stabilizer for the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arupiprazole n=55 Participants Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target. Subjects were administered 24, 12, or 30mg/day of aripiprazole once daily for 154 days in an unblinded manner. Subjects were also administered mood stabilizer concomitantly for 154 days.
Age, Continuous	34.5 years STANDARD_DEVIATION 12.45 • n=93 Participants
Age, Categorical <=18 years	3 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	52 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Sex: Female, Male Female	28 Participants n=93 Participants
Sex: Female, Male Male	27 Participants n=93 Participants
Region of Enrollment Taiwan	5 participants n=93 Participants
Region of Enrollment China	17 participants n=93 Participants
Region of Enrollment Japan	11 participants n=93 Participants
Region of Enrollment Malaysia	6 participants n=93 Participants
Region of Enrollment Indonesia	4 participants n=93 Participants
Region of Enrollment Philippines	12 participants n=93 Participants

PRIMARY outcome

Timeframe: baseline (Day 1 of preceding study), Day 154 or at discontinuation

Outcome measures

Outcome measures
Measure	Aripiprazple n=55 Participants Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target. Subjects were administered 24, 12, or 30mg/day of aripiprazole once daily for 154 days in an unblinded manner. Subjects were also administered mood stabilizer concomitantly for 154 days.
Young Mania Rating Scale (YMRS)	-18.3 scores on a scale Standard Deviation 12.71

SECONDARY outcome

Timeframe: Baseline (Day 1 of preceding study) , Day 154 or at discontinuation

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). 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) was calculated for each treatment group.

Outcome measures

Outcome measures
Measure	Aripiprazple n=55 Participants Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target. Subjects were administered 24, 12, or 30mg/day of aripiprazole once daily for 154 days in an unblinded manner. Subjects were also administered mood stabilizer concomitantly for 154 days.
Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness (Mania)	-2.4 scores on a scale Standard Deviation 1.76

Adverse Events

Aripiprazole

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aripiprazole n=56 participants at risk Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target.
Hepatobiliary disorders Hepatitis	1.8% 1/56 • Number of events 1 • 22 weeks
Nervous system disorders Headache	1.8% 1/56 • Number of events 1 • 22 weeks
Psychiatric disorders Mania	1.8% 1/56 • Number of events 1 • 22 weeks

Other adverse events

Other adverse events
Measure	Aripiprazole n=56 participants at risk Patients who had completed the preceding study but whose condition worsened or remained unchanged or who discontinued the preceding study on Day 14 to Day 21 due to lack of drug efficacy were the target.
Gastrointestinal disorders Constipation	7.1% 4/56 • Number of events 8 • 22 weeks
Gastrointestinal disorders Salivary Hypersecretion	7.1% 4/56 • Number of events 4 • 22 weeks
Gastrointestinal disorders Vomiting	7.1% 4/56 • Number of events 6 • 22 weeks
Gastrointestinal disorders Nausea	5.4% 3/56 • Number of events 4 • 22 weeks
Gastrointestinal disorders Diarrhoea	5.4% 3/56 • Number of events 4 • 22 weeks
General disorders Fatigue	5.4% 3/56 • Number of events 3 • 22 weeks
Infections and infestations Nasopharyngitis	8.9% 5/56 • Number of events 5 • 22 weeks
Investigations Weight Increased	28.6% 16/56 • Number of events 16 • 22 weeks
Investigations Alanine Aminotransferase Increased	7.1% 4/56 • Number of events 4 • 22 weeks
Investigations Blood Creatine Phosphokinase Increased	5.4% 3/56 • Number of events 3 • 22 weeks
Musculoskeletal and connective tissue disorders Muscle Rigidity	7.1% 4/56 • Number of events 4 • 22 weeks
Nervous system disorders Akathisia	21.4% 12/56 • Number of events 13 • 22 weeks
Nervous system disorders Tremor	17.9% 10/56 • Number of events 14 • 22 weeks
Nervous system disorders Somnolence	14.3% 8/56 • Number of events 8 • 22 weeks
Nervous system disorders Headache	8.9% 5/56 • Number of events 6 • 22 weeks
Nervous system disorders Dystonia	5.4% 3/56 • Number of events 3 • 22 weeks
Psychiatric disorders Insomnia	14.3% 8/56 • Number of events 12 • 22 weeks

Additional Information

Director of Clinical Research and Development

Otsuka Pharmaceutical Co, Ltd.

Phone: +81-3-6361-7366

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place