Efficacy, Safety, and Tolerability of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Bipolar I Patients

NCT01567527 | Completed Phase 3 Results DMC

• 1 other identifier: 31-08-250
• Study Type: interventional
• Target: 731
• Locations: 7 countries
• Sites: 76

Brief 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. 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

Keywords

Aripiprazole; Intramuscular (IM) Depot; Bipolar

Outcome Measures

Primary Outcomes (1)

• 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: 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.

  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.

  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.

  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.

  Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).

Study Arms (2)

1

ACTIVE COMPARATOR

Active Comparator: Treatment of Aripiprazole IM Depot

Drug: Intramuscular (IM) Depot Aripiprazole

2

PLACEBO COMPARATOR

Placebo Comparator: Treatment of IM Depot Placebo

Drug: Intramuscular (IM) Depot Placebo

Interventions

Intramuscular (IM) Depot Aripiprazole DRUG

Formulation: Intramuscular (IM) Depot Aripiprazole Formulation 400 mg or 300 mg, once a month injection

1

Intramuscular (IM) Depot Placebo DRUG

Formulation: Intramuscular (IM) Depot Placebo 400 mg or 300 mg, once a month injection

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (76)

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Birmingham, Alabama, United States

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Springdale, Arkansas, United States

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Beverly Hills, California, United States

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Costa Mesa, California, United States

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Escondido, California, United States

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Garden Grove, California, United States

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Los Angeles, California, United States

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National City, California, United States

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Oceanside, California, United States

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Orange, California, United States

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Pico Rivera, California, United States

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Riverside, California, United States

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San Diego, California, United States

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Temecula, California, United States

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Torrance, California, United States

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Lauderhill, Florida, United States

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Leesburg, Florida, United States

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Melbourne, Florida, United States

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Oakland Park, Florida, United States

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Atlanta, Georgia, United States

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Decatur, Georgia, United States

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Smyrna, Georgia, United States

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Hoffman Estates, Illinois, United States

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New Orleans, Louisiana, United States

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Rockville, Maryland, United States

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Flowood, Mississippi, United States

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Saint Charles, Missouri, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Cherry Hill, New Jersey, United States

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Brooklyn, New York, United States

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Buffalo, New York, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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Dayton, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Allentown, Pennsylvania, United States

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Jenkintown, Pennsylvania, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Wichita Falls, Texas, United States

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Richmond, Virginia, United States

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Chatham, Ontario, Canada

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Aizu-Wakamatsu, Fukushima, Japan

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Sapporo, Hokkaido, Japan

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Morioka, Iwate, Japan

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Kawasaki-shi, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kashihara, Nara, Japan

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Sakai, Osaka, Japan

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Sakai-shi, Osaka, Japan

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Fukuoka, Japan

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Itabashi-bu, Japan

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Kanzaki-gun, Japan

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Koriyama-shi, Japan

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Kumamoto, Japan

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Okinawa, Japan

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Shinjuku-ku, Japan

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Tokyo, Japan

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Tottori, Japan

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Toyama, Japan

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Gdynia, Pomeranian Voivodeship, Poland

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Bydgoszcz, Poland

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Chełmno, Poland

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Choroszcz, Poland

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Târgovişte, Dyambovita, Romania

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Bucharest, Romania

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Judet Lasi, Romania

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Anyang-si, Gyeonggi-do, South Korea

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Goyang-si, Gyeonggi-do, South Korea

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Daejeon, South Korea

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Jeju City, South Korea

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Seoul, South Korea

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Keelung, Taiwan

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Taipei, Taiwan

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Taouyuan County, Taiwan

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Related Publications (1)

• 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.

  PMID: 28146613 DERIVED

MeSH Terms

Interventions

Injections, Intramuscular

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Joan Amatniek, Senior Director, Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

joan.amatniek@otsuka-us.com

(609) 512-4464

Study Officials

• Stacy Wu, MD

  Otsuka Pharmaceutical Development and Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2012
• First Posted: March 30, 2012
• Study Start: August 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: August 24, 2018
• Results First Posted: August 24, 2018

Record last verified: 2018-07

Locations

TW (3); RO (3); PL (4); KR (5); US (42); CA (1); JP (18)