Bipolar I DisorderPhase 3NCT00606281

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group-comparison Trial of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode

A Phase 3 study testing Aripiprazole in people with Bipolar I Disorder, run by Otsuka Pharmaceutical Co., Ltd. at 12 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective of this trial is to evaluate the clinical efficacy and safety of aripiprazole in comparison to placebo in patients with Bipolar I Disorder experiencing a manic or mixed episode. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Bipolar I Disorder
What is being tested?: Aripiprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 258 participants
Where: 12 sitesin 4 countries
Study dates: Jan 2008to Nov 2010
Phase: Phase 3
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 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Trial subjects will be men and women of age 18 or above and below the age of 65 who will not be turning 65 during the trial.
Patients have the ability to understand and to provide informed consent to the examination, observation, and evaluation processes specified in this protocol, and have signed the informed consent form based on a full understanding of the trial.
Patients who meet DSM-IV-TR criteria for manic or mixed episodes and have been diagnosed as having "296.4x Bipolar I Disorder in which the most recent episode was manic" or "296.6x Bipolar I Disorder in which the most recent episode was mixed"
Patients with a YMRS total score of 20 or more

Who cannot join

Patients presenting with a clinical picture and/or history that is consistent with a DSM-IV-TR diagnosis of:
Delirium, dementia, amnestic disorder, or other cognitive disorders
Schizophrenia or other psychotic disorder
Personality disorder
Patients experiencing their first manic or mixed episode
Patients whose current manic episode has lasted for more than 4 weeks

Show all 25Show fewer

Patients with psychotic symptoms that are clearly due to another general medical condition or direct physiological effects of a substance
Patients who have met DSM-IV-TR criteria for a substance-related disorder within 3 months (90 days) prior to informed consent (excluding caffeine- and nicotine-related disorders, but including abuse of benzodiazepines)
Patients who have received ECT treatment within 8 weeks prior to informed consent
Patients who are expected to require administration of ultrashort-acting or short-acting benzodiazepine receptor agonist hypnotics and antianxiety drugs (See (1) of 4.2.2) at doses exceeding the equivalent of 15 mg/day of diazepam (Only for those patients using such drugs)
Patients at significant risk of developing a severe adverse event. Patients who have a medical condition that would interfere with assessments of safety or efficacy during the course of the trial, or who have a history of such a condition.
Patients who have received any of the following treatments during the screening period:
Reserpine
Levodopa, dopamine receptor stimulants
Monoamine oxidase inhibitors
Psychostimulants
Thyroid hormones, antithyroid drugs
Corticosteroids (other than topical preparations)
Adrenaline
All other investigational or unapproved agents
ECT
Light therapy
For patients who take lithium, valproate, or carbamazepine within 3 days prior to commencement of investigational product administration, those patients with serum concentrations of lithium greater than 0.6 mmol/L, serum concentrations of valproate greater than 50 µg/mL, or serum concentrations of carbamazepine greater than 4 µg/mL
Patients judged to have a diabetic blood glucose level (judgment based on use of a self-monitoring blood glucose meter permissible), or patients whose HbA1c is 6.5% or higher
Patients with a history or a complication of diabetes

Trial locations and contacts

12 sites in 4 countries.

Country

City, postcode or hospital

12 sites in 4 countries

Japan9 sites

Study site
Chubu Region
Study site
Chugoku Region
Study site
Hokkaido Region
Study site
Hokuriku Region
Study site
Kanto Region
Study site
Kinki Region
Study site
Kyushu Region
Study site
Shikoku Region
Study site
Tohoku Region

Other trials in Japan

China1 site

Study site
Hong Kong

Other trials in China

South Korea1 site

Study site
Seoul

Other trials in South Korea

Taiwan1 site

Study site
Taipei

Other trials in Taiwan

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group-Comparison Trial of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode

The primary objective of this trial is to evaluate the clinical efficacy and safety of aripiprazole in comparison to placebo in patients with Bipolar I Disorder experiencing a manic or mixed episode.

Conditions: Bipolar I Disorder
Being tested: Aripiprazole, placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AripiprazoleDrug
Also called OPC-14597
oral, 24mg/day
placeboDrug
Also called OPC-14597
oral, 0mg(4tablets)/day

Study groups in NCT00606281
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: Aripiprazole
2	Placebo comparator	Not described Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Young Mania Rating Scale (YMRS)
Using LOCF datasets, change in YMRS total score from baseline (Day 1) to endpoint (Day 21) was evaluated through analysis of covariance(ANCOVA).
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) elevated 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).
Measured: Day1, Day21

Secondary outcomes (1)

Clinical Global Impression - Bipolar Version (CGI-BP), Severity of Illness Score (Mania)
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, change in CGI-BP severity of illness score (mania) from baseline (Day 1) to endpoint (Day 21) was evaluated through ANCOVA.
Measured: Day1, Day21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Nov 2010

First posted1 Feb 2008 (estimated)
Study startJan 2008
Primary completionNov 2010
Study completionNov 2010

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.
Other trials for Bipolar I DisorderStudies of the same condition, open and under way.
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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 258 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00606281
Sponsor's protocol ID: 031-06-003
Status last verified: Jan 2014
First submitted: 19 Jan 2008
Last updated: 12 Feb 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
Bipolar Disorder Type I With Mania
RecruitingPhase 2
NMDA Receptor Modulation for the Treatment of Bipolar I Disorder
Bipolar I Disorder
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder
Bipolar-I Disorder With Mania or Mania With Mixed Features
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2)
Bipolar Disorder Type I With Mania or Mania With Mixed Features
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder

All Bipolar I Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group-Comparison Trial of Aripiprazole in the Treatment of Patients With Bipolar Disorder Experiencing a Manic or Mixed Episode
ClinicalTrials.gov ID: NCT00606281
Acronym / sponsor ID: 031-06-003
Conditions: Bipolar I Disorder
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 258 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: Jan 2008
Primary completion: Nov 2010 (actual)
Study completion: Nov 2010 (actual)
First posted: 1 Feb 2008 (estimated)
Results: Posted 12 Feb 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of this trial is to evaluate the clinical efficacy and safety of aripiprazole in comparison to placebo in patients with Bipolar I Disorder experiencing a manic or mixed episode.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: Aripiprazole
2	Placebo comparator	Drug: placebo

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Trial subjects will be men and women of age 18 or above and below the age of 65 who will not be turning 65 during the trial.
Patients have the ability to understand and to provide informed consent to the examination, observation, and evaluation processes specified in this protocol, and have signed the informed consent form based on a full understanding of the trial.
Patients who meet DSM-IV-TR criteria for manic or mixed episodes and have been diagnosed as having "296.4x Bipolar I Disorder in which the most recent episode was manic" or "296.6x Bipolar I Disorder in which the most recent episode was mixed"
Patients with a YMRS total score of 20 or more

Key exclusion criteria (25 listed)

Patients presenting with a clinical picture and/or history that is consistent with a DSM-IV-TR diagnosis of:
Patients experiencing their first manic or mixed episode
Patients whose current manic episode has lasted for more than 4 weeks
Patients with psychotic symptoms that are clearly due to another general medical condition or direct physiological effects of a substance
Patients who have met DSM-IV-TR criteria for a substance-related disorder within 3 months (90 days) prior to informed consent (excluding caffeine- and nicotine-related disorders, but including abuse of benzodiazepines)

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
AripiprazoleAlso: OPC-14597oral, 24mg/day	Drug	1
placeboAlso: OPC-14597oral, 0mg(4tablets)/day	Drug	2

Primary outcome

Young Mania Rating Scale (YMRS)
Time frame: Day1, Day21
Using LOCF datasets, change in YMRS total score from baseline (Day 1) to endpoint (Day 21) was evaluated through analysis of covariance(ANCOVA). 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) elevated 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).

1 secondary outcome

Clinical Global Impression - Bipolar Version (CGI-BP), Severity of Illness Score (Mania)
Time frame: Day1, Day21

Results and safety

Results posted to the registry on 12 Feb 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aripiprazole	128	72
Placebo	130	64

Primary outcome: Young Mania Rating Scale (YMRS)

Time frame: Day1, Day21. Least squares mean (Standard Error). Unit: scores on a scale

Measure	Aripiprazole n = 122	Placebo n = 125
Value	-11.3 (1.31)	-5.3 (1.29)

Aripiprazole vs Placebo: Mean Difference (Final Values): -6.0 (95% CI -9.4 to -2.7), p <0.001, ANCOVA

Population analysed: Full analysis set (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.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 21 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aripiprazole	5 of 123 (4.1%)	69 of 123 (56.1%)	Not reported
Placebo	9 of 125 (7.2%)	45 of 125 (36%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Bipolar I Disorder

RecruitingPhase 3
A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
Bipolar Disorder Type I With Mania
RecruitingPhase 2
NMDA Receptor Modulation for the Treatment of Bipolar I Disorder
Bipolar I Disorder
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder
Bipolar-I Disorder With Mania or Mania With Mixed Features
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2)
Bipolar Disorder Type I With Mania or Mania With Mixed Features
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder

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.

Katsuhisa Saito study director

Department of Clinical Research and Development, Division of New Product Evaluation and Development

12 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aripiprazole in people with Bipolar I Disorder, run by Otsuka Pharmaceutical Co., Ltd. at 12 sites in 4 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 4 inclusion and 25 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 12 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Japan, China, South Korea, Taiwan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 12 Feb 2014). 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?

Young Mania Rating Scale (YMRS) (time frame: Day1, Day21). 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 NCT00606281.

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 12 Feb 2014.