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

NCT ID: NCT01567527

Last Updated: 2018-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 731 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2016-04-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Active Comparator: Treatment of Aripiprazole IM Depot

Group Type: ACTIVE_COMPARATOR

Intramuscular (IM) Depot Aripiprazole

Intervention Type: DRUG

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

2

Placebo Comparator: Treatment of IM Depot Placebo

Group Type: PLACEBO_COMPARATOR

Intramuscular (IM) Depot Placebo

Intervention Type: DRUG

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

Interventions

Intramuscular (IM) Depot Aripiprazole

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

Intervention Type: DRUG

Intramuscular (IM) Depot Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.

2. 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.

3. Subjects currently experiencing a manic episode with a YMRS total score of ≥20 at the Screening Visit.

4. Subjects can have an inpatient or outpatient status prior to entry into Phase C (IM depot stabilization).

5. 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.

Exclusion Criteria

1. Subjects with a current Axis I (DSM-IV-TR) diagnosis other than bipolar I disorder.

2. 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.

3. Subjects with bipolar I disorder who are considered resistant/refractory to treatment for manic symptoms by history.

4. Subjects unresponsive to clozapine for treatment of mania.

5. 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).

6. Subjects with a current manic episode with a duration of > 2 years.

7. 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.

8. 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.

9. Subjects who are currently experiencing a mixed or a depressive episode (per DSM-IV-TR criteria).

10. Subjects with a history of hypersensitivity to antipsychotic agents.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H. Lundbeck A/S

INDUSTRY

Sponsor Role: collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stacy Wu, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development and Commercialization, Inc.

Locations

Birmingham, Alabama, United States

Springdale, Arkansas, United States

Beverly Hills, California, United States

Costa Mesa, California, United States

Escondido, California, United States

Garden Grove, California, United States

Los Angeles, California, United States

National City, California, United States

Oceanside, California, United States

Orange, California, United States

Pico Rivera, California, United States

Riverside, California, United States

San Diego, California, United States

Temecula, California, United States

Torrance, California, United States

Lauderhill, Florida, United States

Leesburg, Florida, United States

Melbourne, Florida, United States

Oakland Park, Florida, United States

Atlanta, Georgia, United States

Decatur, Georgia, United States

Smyrna, Georgia, United States

Hoffman Estates, Illinois, United States

New Orleans, Louisiana, United States

Rockville, Maryland, United States

Flowood, Mississippi, United States

Saint Charles, Missouri, United States

St Louis, Missouri, United States

Lincoln, Nebraska, United States

Cherry Hill, New Jersey, United States

Brooklyn, New York, United States

Buffalo, New York, United States

New York, New York, United States

Cincinnati, Ohio, United States

Dayton, Ohio, United States

Oklahoma City, Oklahoma, United States

Allentown, Pennsylvania, United States

Jenkintown, Pennsylvania, United States

Austin, Texas, United States

Dallas, Texas, United States

Wichita Falls, Texas, United States

Richmond, Virginia, United States

Chatham, Ontario, Canada

Aizu-Wakamatsu, Fukushima, Japan

Sapporo, Hokkaido, Japan

Morioka, Iwate, Japan

Kawasaki-shi, Kanagawa, Japan

Yokohama, Kanagawa, Japan

Kashihara, Nara, Japan

Sakai, Osaka, Japan

Sakai-shi, Osaka, Japan

Fukuoka, , Japan

Itabashi-bu, , Japan

Kanzaki-gun, , Japan

Koriyama-shi, , Japan

Kumamoto, , Japan

Okinawa, , Japan

Shinjuku-ku, , Japan

Tokyo, , Japan

Tottori, , Japan

Toyama, , Japan

Gdynia, Pomeranian Voivodeship, Poland

Bydgoszcz, , Poland

Chełmno, , Poland

Choroszcz, , Poland

Târgovişte, Dyambovita, Romania

Bucharest, , Romania

Judet Lasi, , Romania

Anyang-si, Gyeonggi-do, South Korea

Goyang-si, Gyeonggi-do, South Korea

Daejeon, , South Korea

Jeju City, , South Korea

Seoul, , South Korea

Keelung, , Taiwan

Taipei, , Taiwan

Taouyuan County, , Taiwan

Countries

United States; Canada; Japan; Poland; Romania; South Korea; Taiwan

References

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.

Reference Type: DERIVED

PMID: 28146613 (View on PubMed)

Other Identifiers

31-08-250

Identifier Type: -

Identifier Source: org_study_id