A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder

NCT ID: NCT03257865

Last Updated: 2020-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 333 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-19
• Study Completion Date: 2019-01-22

Brief Summary

To demonstrate the efficacy of brexpiprazole for the acute treatment of manic episodes, with or without mixed features, in participants with a diagnosis of bipolar I disorder.

Detailed Description

A multicenter, randomized, double-blind trial of brexpiprazole versus placebo for the acute treatment of manic episodes, with or without mixed features, associated with bipolar I disorder. This study also demonstrated the safety and tolerability of brexpiprazole in the study population of males and females aged 18 to 65 years (inclusive, at time of consent).

Conditions

Bipolar I Disorder; Manic Episode

Study Design

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

Study Groups

Brexpiprazole

Participants received a starting dose of 2 milligrams (mg)/day brexpiprazole from Days 1 to 3, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4.

Group Type: EXPERIMENTAL

Brexpiprazole

Intervention Type: DRUG

Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.

Placebo

Matching placebo was administered in the same way as brexpiprazole to maintain the blind

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered orally daily for 3 weeks.

Interventions

Brexpiprazole

Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.

Intervention Type: DRUG

Placebo

Administered orally daily for 3 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female participants, ages 18 to 65 years, inclusive, at the time of informed consent.
• Participants willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
• Participants with a Diagnostic & Statistical Manual on Mental Disorders, 5th Edition (DSM-5) diagnosis of bipolar I disorder displaying an acute manic episode with or without mixed features requiring hospitalization. Diagnosis confirmed by the MINI International Neuropsychiatric Interview (MINI) and a history of at least one previous manic episode with or without mixed features with manic symptoms of sufficient severity to require one of the following interventions: hospitalization or treatment with a mood stabilizer, or treatment with an antipsychotic agent. "Require" was defined as an intervention that occurred rather than one that was recommended.
• Young-mania rating scale (YMRS) score of ≥ 24 at screening and baseline

Exclusion Criteria

• Sexually active male or women of childbearing potential (WOCBP) who did not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product (IMP).
• Females who were breastfeeding and/or who had a positive pregnancy test result prior to receiving trial medication.
• Participants considered unresponsive to clozapine or who were only responsive to clozapine.
• Participants with a history of DSM-5 diagnosis other than bipolar I disorder, including schizophrenia, schizoaffective disorder, major depressive disorder, attention-deficit/hyperactivity disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. All other current diagnoses must have been discussed with the medical monitor.
• Participants whose current manic episode had lasted for more than 4 weeks overall, or who had required hospitalization > 21 days for the current acute episode at the time of the screening visit, excluding hospitalization for psychosocial reasons.
• Participant with manic symptoms better accounted for by another general medical condition or direct physiological effect of substance (for example, medications).
• Participants who have had electroconvulsive treatment within the past 2 months.
• Participants with a positive drug screen for cocaine or other illicit drugs.
• Abnormal laboratory test results, vital signs or electrocardiogram findings, unless, based on investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results.
• Rapid cyclers with more than 6 episodes in the previous year.
• Participants with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least the past 90 days) or an abnormal result for free thyroxine at screening.
• Participants with uncontrolled hypertension or symptomatic hypotension or orthostatic hypotension.
• Participants with epilepsy or history of seizures.
• Participants who participated in a clinical trial within the last 60 days or who participated in more than 2 clinical trials within the past year.
• Use of psychotropic medications (other than benzodiazepines) within 7 days of the baseline YMRS.
• Participants who currently had clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
• Participants who received brexpiprazole in any prior clinical trial or currently taking commercially available brexpiprazole (Rexulti).

• 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

Matthew Leoni, M.D.

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

Atria Clinical Research

Little Rock, Arkansas, United States

Woodland International Research Group, LLC

Little Rock, Arkansas, United States

CiTrials

Bellflower, California, United States

CNS Research Science Inc.

Cerritos, California, United States

Apostle Clinical Trials

Long Beach, California, United States

CNRI-San Diego

San Diego, California, United States

Artemis Institute for Clinical Research

San Diego, California, United States

CiTrials

Santa Ana, California, United States

Collaborative Neuroscience Network, LLC

Torrance, California, United States

Shreenath Clinical Service

Yorba Linda, California, United States

Galiz Research

Hialeah, Florida, United States

Research Centers of America LLC

Hollywood, Florida, United States

Optimus U Corporation

Miami, Florida, United States

South Florida Research Phase I-IV

Miami Springs, Florida, United States

Meridien Research

Orlando, Florida, United States

iResearch Atlanta, LLC

Decatur, Georgia, United States

Uptown Research Institute LLC

Chicago, Illinois, United States

Neuropsychiatric Research & Associates, LTD

Winfield, Illinois, United States

Louisiana Clinical Research

Shreveport, Louisiana, United States

Arch Clinical Trials, LLC

St Louis, Missouri, United States

St Louis Clinical Trials LLC

St Louis, Missouri, United States

Hassman Research Institute

Berlin, New Jersey, United States

CNS Research Science, Inc.

Jamaica, New York, United States

New Hope Clinical Research

Charlotte, North Carolina, United States

University of Cincinnati Department of Psychiatry and Behavorial Science

Cincinnati, Ohio, United States

InSite Clinical Research LLC

DeSoto, Texas, United States

Pillar Clinical Research, LLC

Richardson, Texas, United States

Clinical Hospital Centre Rijeka

Rijeka, , Croatia

Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov

Dnipro, , Ukraine

SI ""Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Sciences of Ukraine

Kharkiv, , Ukraine

Communal Establishment "Kherson Regional Psychiatric Hospital" of Kherson Regional Council

Kherson, , Ukraine

Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic disorders

Kyiv, , Ukraine

Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #20

Lviv, , Ukraine

Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #25

Lviv, , Ukraine

Communal Establishment "Odesa Regional Psychiatric Hospital #2

Oleksandrivka, , Ukraine

O.F. Maltsev Poltava Regional Psychiatric Hospital

Poltava, , Ukraine

Ternopil Regional Municipal Clinical Psychoneurolgical Hospital

Ternopil, , Ukraine

Communal Establishment "Acad. O.I. Iushchenko Vinnytsia Regional Psychoneurologic Hospital"

Vinnytsia, , Ukraine

Countries

United States; Croatia; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

331-201-00081

Identifier Type: -

Identifier Source: org_study_id