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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01567527
First received: March 26, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Bipolar I Disorder
Drug: Intramuscular (IM) Depot Aripiprazole
Drug: Intramuscular (IM) Depot Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Time from randomization to recurrence of any mood episode during Double-Bind Placebo Controlled phase [ Time Frame: Up to 52 weeks from randomization ] [ Designated as safety issue: No ]
    Efficacy evaluations will be assessed using the following instruments: YMRS, MADRS, CGI-BP-S, and CGI-BP Change from Preceding Phase.


Secondary Outcome Measures:
  • Proportion of subjects meeting criteria for recurrence of any mood episode(manic, mixed, depressive) [ Time Frame: Up to 52 weeks from randomization ] [ Designated as safety issue: No ]
  • Mean change from randomization to endpoint in the CGI-BP-S (mania) score [ Time Frame: Up to 52 weeks from randomization ] [ Designated as safety issue: No ]
  • Time from randomization to recurrence defined by hospitalization for a mood episode. [ Time Frame: Up to 52 weeks from randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 688
Study Start Date: August 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Active Comparator: Treatment of Aripiprazole IM Depot
Drug: Intramuscular (IM) Depot Aripiprazole
Formulation: Intramuscular (IM) Depot Aripiprazole Formulation 400 mg or 300 mg, once a month injection
Placebo Comparator: 2
Placebo Comparator: Treatment of IM Depot Placebo
Drug: Intramuscular (IM) Depot Placebo
Formulation: Intramuscular (IM) Depot Placebo 400 mg or 300 mg, once a month injection

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567527

Contacts
Contact: INC Research sm_opdc.ctgov@incresearch.com

  Show 78 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
H. Lundbeck A/S
Investigators
Study Director: Stacy Wu, MD Otsuka Pharmaceutical Development and Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01567527     History of Changes
Other Study ID Numbers: 31-08-250
Study First Received: March 26, 2012
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan : Food and Drug Administration
Canada: Health Canada

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Aripiprazole
Intramuscular (IM) Depot
Bipolar

Additional relevant MeSH terms:
Disease
Pathologic Processes
Aripiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on September 22, 2014