Bipolar I DisorderPhase 3NCT01567527
Efficacy, Safety, and Tolerability of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Bipolar I Patients
A Phase 3 study testing Intramuscular (IM) Depot Aripiprazole in people with Bipolar I Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 76 sites in 7 countries.
Trial summary
This will be a randomized, double-blind, placebo-controlled trial to assess the time to recurrence of any mood episode in subjects with bipolar I disorder who have maintained stability on aripiprazole IM depot for at least 8 weeks. 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?
- Intramuscular (IM) Depot Aripiprazole
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 731 participants
- Where
- 76 sitesin 7 countries
- Study dates
- Aug 2012to Apr 2016
- 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
- Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
- Subjects with a current diagnosis of bipolar I disorder, as defined by DSM-IV-TR criteria and confirmed by the MINI and a history of at least one previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent, in addition to their current manic episode. "Require" is defined as an intervention that occurred rather than one that was recommended. Rapid cyclers with 8 or fewer episodes in the previous year will be included.
- Subjects currently experiencing a manic episode with a YMRS total score of ≥20 at the Screening Visit.
- Subjects can have an inpatient or outpatient status prior to entry into Phase C (IM depot stabilization).
- In the investigator's opinion, subjects who are able to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, aripiprazole IM depot injection, and discontinuation of prohibited concomitant medications; who can read and understand the written word in order to complete subject-reported outcomes measures; and who can be reliably rated on assessment scales.
Who cannot join
- Subjects with a current Axis I (DSM-IV-TR) diagnosis other than bipolar I disorder.
- Subjects who have NOT experienced at least one previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and /or treatment with an antipsychotic agent, excluding their current manic episode. "Require" is defined as a intervention that occurred rather than one that was recommended.
- Subjects with bipolar I disorder who are considered resistant/refractory to treatment for manic symptoms by history.
- Subjects unresponsive to clozapine for treatment of mania.
- Subjects with a significant risk of committing suicide based on history, mental status examination, investigator's judgment, or C-SSRS answer of "yes" to question 4 or 5 (current or within the last 90 days).
- Subjects with a current manic episode with a duration of > 2 years.
Show all 10Show fewer
- Subjects who currently (within the past month) meet DSM-IV-TR criteria for substance abuse or substance dependence; this includes the abuse of alcohol and benzodiazepines, but excludes the use of caffeine and/or nicotine.
- Subjects who have a history or evidence of a medical condition that would expose them to an undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as determined by the clinical judgment of the investigator.
- Subjects who are currently experiencing a mixed or a depressive episode (per DSM-IV-TR criteria).
- Subjects with a history of hypersensitivity to antipsychotic agents.
Trial locations and contacts
76 sites in 7 countries.
76 sites in 7 countries
United States42 sites
Study site
Allentown, Pennsylvania
Study site
Atlanta, Georgia
Study site
Austin, Texas
Study site
Beverly Hills, California
Study site
Birmingham, Alabama
Study site
Brooklyn, New York
Study site
Buffalo, New York
Study site
Cherry Hill, New Jersey
Study site
Cincinnati, Ohio
Study site
Costa Mesa, California
Study site
Dallas, Texas
Study site
Dayton, Ohio
Study site
Decatur, Georgia
Study site
Escondido, California
Study site
Flowood, Mississippi
Study site
Garden Grove, California
Study site
Hoffman Estates, Illinois
Study site
Jenkintown, Pennsylvania
Study site
Lauderhill, Florida
Study site
Leesburg, Florida
Study site
Lincoln, Nebraska
Study site
Los Angeles, California
Study site
Melbourne, Florida
Study site
National City, California
Study site
New Orleans, Louisiana
Study site
New York, New York
Study site
Oakland Park, Florida
Study site
Oceanside, California
Study site
Oklahoma City, Oklahoma
Study site
Orange, California
Study site
Pico Rivera, California
Study site
Richmond, Virginia
Study site
Riverside, California
Study site
Rockville, Maryland
Study site
Saint Charles, Missouri
Study site
San Diego, California
Study site
Smyrna, Georgia
Study site
Springdale, Arkansas
Study site
St Louis, Missouri
Study site
Temecula, California
Study site
Torrance, California
Study site
Wichita Falls, Texas
Japan18 sites
Study site
Aizu-Wakamatsu, Fukushima
Study site
Fukuoka
Study site
Itabashi-bu
Study site
Kanzaki-gun
Study site
Kashihara, Nara
Study site
Kawasaki-shi, Kanagawa
Study site
Koriyama-shi
Study site
Kumamoto
Study site
Morioka, Iwate
Study site
Okinawa
Study site
Sakai, Osaka
Study site
Sakai-shi, Osaka
Study site
Sapporo, Hokkaido
Study site
Shinjuku-ku
Study site
Tokyo
Study site
Tottori
Study site
Toyama
Study site
Yokohama, Kanagawa
South Korea5 sites
Study site
Anyang-si, Gyeonggi-do
Study site
Daejeon
Study site
Goyang-si, Gyeonggi-do
Study site
Jeju City
Study site
Seoul
Poland4 sites
Study site
Bydgoszcz
Study site
Chełmno
Study site
Choroszcz
Study site
Gdynia, Pomeranian Voivodeship
Romania3 sites
Study site
Bucharest
Study site
Judet Lasi
Study site
Targoviste, Dyambovita
About this study
Official title: 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of an Intramuscular Depot Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder
This will be a randomized, double-blind, placebo-controlled trial to assess the time to recurrence of any mood episode in subjects with bipolar I disorder who have maintained stability on aripiprazole IM depot for at least 8 weeks. This trial will include male and female subjects 18 to 65 years of age, inclusive, with a diagnosis of bipolar I disorder, according to DSM-IV-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI), who have experienced at least one previous manic episode of sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic agent in addition to their current manic episode. All subjects must be experiencing a manic episode (per DSM-IV-TR criteria) with a YMRS total score ≥ 20 at trial entry. Both inpatients and outpatients are eligible for this trial.
This trial will consist of a screening phase followed by 4 treatment phases. Subjects will undergo screening for eligibility, followed by a conversion to oral aripiprazole monotherapy phase, if needed, an oral aripiprazole stabilization phase, a single-blind aripiprazole IM depot stabilization phase, and, a double-blind, placebo-controlled phase.
- Conditions
- Bipolar I Disorder
- Being tested
- Intramuscular (IM) Depot Aripiprazole, Intramuscular (IM) Depot Placebo
- Keywords
- Aripiprazole, Intramuscular (IM) Depot, Bipolar
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intramuscular (IM) Depot AripiprazoleDrug
Formulation: Intramuscular (IM) Depot Aripiprazole Formulation 400 mg or 300 mg, once a month injection
Intramuscular (IM) Depot PlaceboDrug
Formulation: Intramuscular (IM) Depot Placebo 400 mg or 300 mg, once a month injection
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Active Comparator: Treatment of Aripiprazole IM Depot Receives: Drug: Intramuscular (IM) Depot Aripiprazole |
| 2 | Placebo comparator | Placebo Comparator: Treatment of IM Depot Placebo Receives: Drug: Intramuscular (IM) Depot Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time From Randomization to Recurrence of Any Mood Episode During Double-bind Placebo-controlled Phase.
This endpoint was defined as meeting any of the following criteria:
- Hospitalization for any mood episode OR
- Any of the following:
- YMRS total score ≥ 15 OR
- MADRS total score ≥ 15 OR
- CGI-BP-S score > 4 (overall score) OR
- SAE of worsening disease (bipolar I disorder) OR
- Discontinuation due to lack of efficacy or discontinuation due to an AE of worsening disease OR
- Clinical worsening with the need for treatment of symptoms of an underlying mood disorder by addition of a mood stabilizer, antidepressant treatment, antipsychotic medication, or increase greater than the allowed benzodiazepine doses, or
- Active suicidality, which is defined as a score of 4 or more on the MADRS item 10 OR an answer of "yes" on question 4 or 5 on the C-SSRS.
The time to event is presented in the following table.
Measured: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).
Secondary outcomes (3)
Number of Subjects Meeting Criteria for Recurrence of Any Mood Episode.
To assess the proportion of subjects who met criteria for recurrence of any mood episode (manic, mixed or depressive). Hierarchical procedure was used to preserve the overall Type I error at 0.05.
Measured: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).
Mean Change From Randomization to Endpoint in the CGI-BP-S (Mania) Score.
CGI-BP-S assessed the subject's severity of Illness (mania) based on a 7-point scale ranging from 1 (normal/ not ill at all) to 7 (very severely ill).
Measured: Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).
Time From Randomization to Recurrence Defined by Hospitalization for a Mood Episode.
Analysis of time from randomization to recurrence defined by hospitalization for a mood episode (Double-blind, Placebo-controlled Phase efficacy sample).
Time to recurrence is presented in the following table.
Measured: Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2012 (estimated)
- Study startAug 2012
- Primary completionApr 2016
- Study completionApr 2016
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 I 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 731 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Sponsor
- Investigators
- Stacy Wu, MD, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01567527
- Sponsor's protocol ID
- 31-08-250
- Status last verified
- Jul 2018
- First submitted
- 26 Mar 2012
- Last updated
- 24 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, Perry P, Hertel P, Such P, Salzman PM, McQuade RD, Nyilas M, Carson WH. Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled, 52-Week Randomized Withdrawal Study. J Clin Psychiatry. 2017 Mar;78(3):324-331. doi: 10.4088/JCP.16m11201.
PubMed 28146613
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of an Intramuscular Depot Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder
- ClinicalTrials.gov ID
- NCT01567527
- Acronym / sponsor ID
- 31-08-250
- Conditions
- Bipolar I Disorder
- Keywords
- Aripiprazole, Intramuscular (IM) Depot, Bipolar
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 731 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Study start
- Aug 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 30 Mar 2012 (estimated)
- Results
- Posted 24 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a randomized, double-blind, placebo-controlled trial to assess the time to recurrence of any mood episode in subjects with bipolar I disorder who have maintained stability on aripiprazole IM depot for at least 8 weeks. This trial will include male and female subjects 18 to 65 years of age, inclusive, with a diagnosis of bipolar I disorder, according to DSM-IV-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI), who have experienced at least one previous manic episode of sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic agent in addition to their current manic episode. All subjects must be experiencing a manic episode (per DSM-IV-TR criteria) with a YMRS total score ≥ 20 at trial entry. Both inpatients and outpatients are eligible for this trial.
This trial will consist of a screening phase followed by 4 treatment phases. Subjects will undergo screening for eligibility, followed by a conversion to oral aripiprazole monotherapy phase, if needed, an oral aripiprazole stabilization phase, a single-blind aripiprazole IM depot stabilization phase, and, a double-blind, placebo-controlled phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Intramuscular (IM) Depot AripiprazoleActive Comparator: Treatment of Aripiprazole IM Depot |
| 2 | Placebo comparator | Drug: Intramuscular (IM) Depot PlaceboPlacebo Comparator: Treatment of IM Depot Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
- Subjects with a current diagnosis of bipolar I disorder, as defined by DSM-IV-TR criteria and confirmed by the MINI and a history of at least one previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent, in addition to their current manic episode. "Require" is defined as an intervention that occurred rather than one that was recommended. Rapid cyclers with 8 or fewer episodes in the previous year will be included.
- Subjects currently experiencing a manic episode with a YMRS total score of ≥20 at the Screening Visit.
- Subjects can have an inpatient or outpatient status prior to entry into Phase C (IM depot stabilization).
- In the investigator's opinion, subjects who are able to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, aripiprazole IM depot injection, and discontinuation of prohibited concomitant medications; who can read and understand the written word in order to complete subject-reported outcomes measures; and who can be reliably rated on assessment scales.
Key exclusion criteria (10 listed)
- Subjects with a current Axis I (DSM-IV-TR) diagnosis other than bipolar I disorder.
- Subjects who have NOT experienced at least one previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and /or treatment with an antipsychotic agent, excluding their current manic episode. "Require" is defined as a intervention that occurred rather than one that was recommended.
- Subjects with bipolar I disorder who are considered resistant/refractory to treatment for manic symptoms by history.
- Subjects unresponsive to clozapine for treatment of mania.
- Subjects with a significant risk of committing suicide based on history, mental status examination, investigator's judgment, or C-SSRS answer of "yes" to question 4 or 5 (current or within the last 90 days).
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 |
|---|---|---|
| Intramuscular (IM) Depot AripiprazoleFormulation: Intramuscular (IM) Depot Aripiprazole Formulation 400 mg or 300 mg, once a month injection | Drug | 1 |
| Intramuscular (IM) Depot PlaceboFormulation: Intramuscular (IM) Depot Placebo 400 mg or 300 mg, once a month injection | Drug | 2 |
Primary outcome
Time From Randomization to Recurrence of Any Mood Episode During Double-bind Placebo-controlled Phase.
Time frame: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).
This endpoint was defined as meeting any of the following criteria: 1. Hospitalization for any mood episode OR 2. Any of the following: 1. YMRS total score ≥ 15 OR 2. MADRS total score ≥ 15 OR 3. CGI-BP-S score > 4 (overall score) OR 3. SAE of worsening disease (bipolar I disorder) OR 4. Discontinuation due to lack of efficacy or discontinuation due to an AE of worsening disease OR 5. Clinical worsening with the need for treatment of symptoms of an underlying mood disorder by addition of a mood stabilizer, antidepressant treatment, antipsychotic medication, or increase greater than the allowed benzodiazepine doses, or 6. Active suicidality, which is defined as a score of 4 or more on the MADRS item 10 OR an answer of "yes" on question 4 or 5 on the C-SSRS. The time to event is presented in the following table.
3 secondary outcomes
Number of Subjects Meeting Criteria for Recurrence of Any Mood Episode.
Time frame: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).
Mean Change From Randomization to Endpoint in the CGI-BP-S (Mania) Score.
Time frame: Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).
Time From Randomization to Recurrence Defined by Hospitalization for a Mood Episode.
Time frame: Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28146613Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, Perry P, Hertel P, Such P, Salzman PM, McQuade RD, Nyilas M, Carson WH. Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled, 52-Week Randomized Withdrawal Study. J Clin Psychiatry. 2017 Mar;78(3):324-331. doi: 10.4088/JCP.16m11201.
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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.
Stacy Wu, MD study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
76 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intramuscular (IM) Depot Aripiprazole in people with Bipolar I Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 76 sites in 7 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 5 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 24 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 76 sites in United States, Japan, South Korea, Poland, Romania and 2 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 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 24 Aug 2018). 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?
Time From Randomization to Recurrence of Any Mood Episode During Double-bind Placebo-controlled Phase. (time frame: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).). 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 NCT01567527, 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 24 Aug 2018.