Clinical trial NCT01567527: Efficacy, Safety, and Tolerability of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Bipolar I Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar I Disorder
Keywords: Aripiprazole
Intramuscular (IM) Depot
Bipolar
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2012-03-30
Enrollment: 731
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Time From Randomization to Recurrence of Any Mood Episode During Double-bind Placebo-controlled Phase.
timeFrame: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).
Secondary outcomes:
measure: Number of Subjects Meeting Criteria for Recurrence of Any Mood Episode.
timeFrame: Baseline of the Double-blind, Placebo-controlled Phase Up to the end of the study (Week 52).
measure: Mean Change From Randomization to Endpoint in the CGI-BP-S (Mania) Score.
timeFrame: Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).
measure: Time From Randomization to Recurrence Defined by Hospitalization for a Mood Episode.
timeFrame: Baseline of the Double-blind, Placebo-controlled Phase up to the end of the study (Week 52).
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Springdale
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: Costa Mesa
country: United States
state: California
city: Escondido
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: National City
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Orange
country: United States
state: California
city: Pico Rivera
country: United States
state: California
city: Riverside
country: United States
state: California
city: San Diego
country: United States
state: California
city: Temecula
country: United States
state: California
city: Torrance
country: United States
state: California
city: Lauderhill
country: United States
state: Florida
city: Leesburg
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Oakland Park
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Smyrna
country: United States
state: Georgia
city: Hoffman Estates
country: United States
state: Illinois
city: New Orleans
country: United States
state: Louisiana
city: Rockville
country: United States
state: Maryland
city: Flowood
country: United States
state: Mississippi
city: Saint Charles
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Cherry Hill
country: United States
state: New Jersey
city: Brooklyn
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Allentown
country: United States
state: Pennsylvania
city: Jenkintown
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Wichita Falls
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Chatham
country: Canada
state: Ontario
city: Aizu Wakamatsu
country: Japan
state: Fukusima
city: Sapporo
country: Japan
state: Hokkaido
city: Morioka
country: Japan
state: Iwate
city: Kawasaki-shi
country: Japan
state: Kanagawa
city: Yokohama-shi
country: Japan
state: Kanagawa
city: Yokohama
country: Japan
state: Kanagawa
city: Kashihara
country: Japan
state: Nara
city: Sakai-shi
country: Japan
state: Osaka
city: Sakai
country: Japan
state: Osaka
city: Fukuoka
country: Japan
city: Itabashi-bu
country: Japan
city: Kanzaki-gun
country: Japan
city: Koriyama-shi
country: Japan
city: Kumamoto
country: Japan
city: Okinawa
country: Japan
city: Shinjuku-ku
country: Japan
city: Tokyo
country: Japan
city: Tottori
country: Japan
city: Toyama
country: Japan
city: Anyang-si
country: Korea, Republic of
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
state: Gyeonggi-do
city: Daejeon
country: Korea, Republic of
city: Jeju-si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Gdynia
country: Poland
state: Pomorskie
city: Bydgoszcz
country: Poland
city: Chelmno
country: Poland
city: Choroszcz
country: Poland
city: Targoviste
country: Romania
state: Dyambovita
city: Bucharest
country: Romania
city: Judet Lasi
country: Romania
city: Keelung City
country: Taiwan
city: Taipei
country: Taiwan
city: Taouyuan County
country: Taiwan
Study officials:
affiliation: Otsuka Pharmaceutical Development and Commercialization, Inc.
name: Stacy Wu, MD
role: STUDY_DIRECTOR
References:
citation: 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.