Major Depressive DisorderPhase 3NCT00876343

Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder

A Phase 3 study testing Aripiprazole (Fixed dose) and Aripiprazole (Titrated dose) in people with Major Depressive Disorder, run by Otsuka Pharmaceutical Co., Ltd. at 8 sites in Japan.

Completed

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

Official record

Search all trials

Trial summary

To examine the efficacy and safety of aripiprazole versus placebo as an adjunctive therapy co-administered with either an selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) in patients with major depressive disorder. Read more about this study

Who is it for?: Ages 20 to 74 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: Aripiprazole (Fixed dose) and Aripiprazole (Titrated dose)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 586 participants
Where: 8 sitesJapan
Study dates: Mar 2009to Jul 2012
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 20 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients who are either inpatients or outpatients
Patients who 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 diagnosed as having either "296.2x Major Depressive Disorder, Single Episode" or "296.3x Major Depressive Disorder, Recurrent" according to DSM-IV-TR, and for whom the current episode of major depressive disorder has been ongoing for more than 8 weeks
Patients with a HAM-D17 total score of 18 or more

Who cannot join

Female patients of child bearing potential who wish to become pregnant during the treatment period, or within 4 weeks after study completion/discontinuation
Female patients who are pregnant, possibly pregnant, or breast feeding
Patients judged to be unable to tolerate any type of antidpressant treatment (including drugs not being used in the current episode of major depressive disorder), based on treatment history to date
Patients who have previously received electro-convulsive therapy
Patients who have participated in clinical studies on medical devices or other drugs within the past month
Patients at risk of having serious adverse events or developing symptoms that could interfere with safety and efficacy evaluations (such as symptoms of fibromyalgia syndrome overlapping with symptoms of depression), based on previous medical history

Show all 10Show fewer

Patients with a history or a complication of diabetes
Patients with thyroid disease (excluding patients who are stabilized on drug therapy for at least 3 months)
Patients with a history of serotonin syndrome or psychotropic neuroleptic malignant syndrome
Patients with a history of seizure disorder (epilepsy etc.)

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

Japan8 sites

Study site
Chubu Region
Study site
Chugoku Region
Study site
Hokkaido 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

About this study

Official title: Placebo-Controlled, Double-Blind, Parallel Group-Comparison Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder

Conditions: Major Depressive Disorder
Being tested: Aripiprazole (Fixed dose), Aripiprazole (Titrated dose), Placebo
Medical subject headings: Depressive Disorder, Major

What participants receive

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

Aripiprazole (Fixed dose)Drug
Also called Aripiprazole
administered orally once daily, 3 mg daily, 6 weeks
Aripiprazole (Titrated dose)Drug
Also called Aripiprazole
administered orally once daily, 3 to 15 mg daily, 6 weeks
PlaceboDrug
Also called Placebo of aripiprazole
administered orally once daily, 6 weeks

Study groups in NCT00876343
Study group	Role	What they receive
1	Experimental	Fixed dose Receives: Drug: Aripiprazole (Fixed dose)
2	Experimental	Titration dose Receives: Drug: Aripiprazole (Titrated dose)
3	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

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

Mean Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The change in MADRS total score from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period by covariance analysis, and compared the aripiprazole variable dose group with the placebo group as well as the aripiprazole fixed dose group with the placebo group.
Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
The questionnaire includes questions on the following symptoms
1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts
Measured: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration

Secondary outcomes (2)

MADRS Response Rate
The percentage of subjects with a decrease in MADRS total score of 50% or more, from the end of the SSRI/SNRI treatment period to the end of the placebo-controlled, double-blind treatment period (or withdrawal).
Measured: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration
Mean Change in Sheehan Disability Scale (SDISS)
The endpoint evaluated the change in SDISS from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period.
The patient rates the extent to which his or her 1) work, 2) social life or leisure activities, and 3) home life or family responsibilities are impaired by his or her symptoms on a 10-point visual analog scale. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).
Measured: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration

Timeline

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

Mar 2009Jul 2012

First posted6 Apr 2009 (estimated)
Study startMar 2009
Primary completionJul 2012
Study completionJul 2012

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 (2)Papers the sponsor has linked to this study.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by Otsuka Pharmaceutical Co., Ltd.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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 586 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00876343
Sponsor's protocol ID: 031-08-001
Other IDs: JapicCTI-090724
Status last verified: Dec 2013
First submitted: 2 Apr 2009
Last updated: 10 Feb 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Ozaki N, Otsubo T, Kato M, Higuchi T, Ono H, Kamijima K; ADMIRE Study Group. Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Asberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study. Psychiatry Clin Neurosci. 2015 Jan;69(1):34-42. doi: 10.1111/pcn.12214. Epub 2014 Aug 4.
PubMed 24965202
Kamijima K, Higuchi T, Ishigooka J, Ohmori T, Ozaki N, Kanba S, Kinoshita T, Koyama T; ADMIRE Study Group. Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: a randomized, double-blind, placebo-controlled study (ADMIRE study). J Affect Disord. 2013 Dec;151(3):899-905. doi: 10.1016/j.jad.2013.07.035. Epub 2013 Aug 28.
PubMed 24074484

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

Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Placebo-Controlled, Double-Blind, Parallel Group-Comparison Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder
ClinicalTrials.gov ID: NCT00876343
Acronym / sponsor ID: 031-08-001
Conditions: Major Depressive Disorder
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 586 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: Mar 2009
Primary completion: Jul 2012 (actual)
Study completion: Jul 2012 (actual)
First posted: 6 Apr 2009 (estimated)
Results: Posted 10 Feb 2014

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
1	Experimental	Drug: Aripiprazole (Fixed dose)Fixed dose
2	Experimental	Drug: Aripiprazole (Titrated dose)Titration dose
3	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 20 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patients who are either inpatients or outpatients
Patients who 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 diagnosed as having either "296.2x Major Depressive Disorder, Single Episode" or "296.3x Major Depressive Disorder, Recurrent" according to DSM-IV-TR, and for whom the current episode of major depressive disorder has been ongoing for more than 8 weeks
Patients with a HAM-D17 total score of 18 or more

Key exclusion criteria (10 listed)

Female patients of child bearing potential who wish to become pregnant during the treatment period, or within 4 weeks after study completion/discontinuation
Female patients who are pregnant, possibly pregnant, or breast feeding
Patients judged to be unable to tolerate any type of antidpressant treatment (including drugs not being used in the current episode of major depressive disorder), based on treatment history to date
Patients who have previously received electro-convulsive therapy
Patients who have participated in clinical studies on medical devices or other drugs within the past month

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
Aripiprazole (Fixed dose)Also: Aripiprazoleadministered orally once daily, 3 mg daily, 6 weeks	Drug	1
Aripiprazole (Titrated dose)Also: Aripiprazoleadministered orally once daily, 3 to 15 mg daily, 6 weeks	Drug	2
PlaceboAlso: Placebo of aripiprazoleadministered orally once daily, 6 weeks	Drug	3

Primary outcome

Mean Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration
The change in MADRS total score from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period by covariance analysis, and compared the aripiprazole variable dose group with the placebo group as well as the aripiprazole fixed dose group with the placebo group. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts

2 secondary outcomes

MADRS Response Rate
Time frame: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration
Mean Change in Sheehan Disability Scale (SDISS)
Time frame: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration

Results and safety

Results posted to the registry on 10 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
Variable Dose Group of Aripiprazole	194	177
Fixed Dose Group of Aripiprazole	197	180
Placebo Group	195	183

Primary outcome: Mean Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

Time frame: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration. Mean (Standard Error). Unit: Rating score

Measure	Variable Dose Group of Aripiprazole n = 194	Fixed Dose Group of Aripiprazole n = 197	Placebo Group n = 195
Value	-9.6 (0.6)	-10.5 (0.6)	-7.4 (0.6)

Variable Dose Group of Aripiprazole vs Placebo Group: Mean Difference (Final Values): -2.2 (95% CI -3.7 to -0.6), p = 0.006, ANCOVA
Fixed Dose Group of Aripiprazole vs Placebo Group: Mean Difference (Final Values): -3.1 (95% CI -4.6 to -1.5), p <0.001, ANCOVA

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 weeks. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Variable Dose Group of Aripiprazole	3 of 194 (1.5%)	140 of 194 (72.2%)	Not reported
Fixed Dose Group of Aripiprazole	2 of 197 (1%)	122 of 197 (61.9%)	Not reported
Placebo Group	2 of 195 (1%)	92 of 195 (47.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24965202Ozaki N, Otsubo T, Kato M, Higuchi T, Ono H, Kamijima K; ADMIRE Study Group. Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Asberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study. Psychiatry Clin Neurosci. 2015 Jan;69(1):34-42. doi: 10.1111/pcn.12214. Epub 2014 Aug 4.
Derived from this study: PubMed 24074484Kamijima K, Higuchi T, Ishigooka J, Ohmori T, Ozaki N, Kanba S, Kinoshita T, Koyama T; ADMIRE Study Group. Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: a randomized, double-blind, placebo-controlled study (ADMIRE study). J Affect Disord. 2013 Dec;151(3):899-905. doi: 10.1016/j.jad.2013.07.035. Epub 2013 Aug 28.

Related trials for Major Depressive Disorder

Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

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

OPC-J

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aripiprazole (Fixed dose) and Aripiprazole (Titrated dose) in people with Major Depressive Disorder, run by Otsuka Pharmaceutical Co., Ltd. at 8 sites in Japan.

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 10 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 10 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 8 sites in Japan. 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 10 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?

Mean Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (time frame: Baseline (the end of the SSRI/SNRI treatment period), at completion of administration). 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 NCT00876343, which also lists 2 linked publications.

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 10 Feb 2014.