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

NCT ID: NCT03259555

Last Updated: 2020-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 322 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-14
• Study Completion Date: 2019-01-02

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 and a history of at least 1 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 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.
• 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, medication).
• 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 or 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.
• Participant 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

Woodland International Research Group

Little Rock, Arkansas, United States

Woodland Research Northwest, LLC

Rogers, Arkansas, United States

ProScience Research Group

Culver City, California, United States

Collaborative Neuroscience Network, LLC

Garden Grove, California, United States

Behavioral Research Specialists, LLC

Glendale, California, United States

Pacific Research Partners, LLC

Oakland, California, United States

NRC Research Institute

Orange, California, United States

Asclepes Research Centers

Panorama City, California, United States

Ci Trials

Riverside, California, United States

Sharp Vista Hospital

San Diego, California, United States

Galiz Research

Hialeah, Florida, United States

Advanced Research Institute of Miami

Homestead, Florida, United States

Florida Behavioral Medicine

Largo, Florida, United States

Optimus U Corporation

Miami, Florida, United States

Behavioral Clinical Research, Inc.

North Miami, Florida, United States

Segal Trials

North Miami, Florida, United States

Radiant Research Inc.

Atlanta, Georgia, United States

Alexian Brothers Center for Psychiatric Research

Hoffman Estates, Illinois, United States

CBH Health

Gaithersburg, Maryland, United States

Advanced Clinical Research Center, LLC

St Louis, Missouri, United States

Richard H Weisler, MD, PA, and Associates

Raleigh, North Carolina, United States

SP Research PLLC

Oklahoma City, Oklahoma, United States

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Carolina Clinical Trials, Inc.

Charleston, South Carolina, United States

University of Texas at Austin

Austin, Texas, United States

Community Clinical Research, Inc.

Austin, Texas, United States

Pillar Clinical Research, LLC

Garland, Texas, United States

Pillar Clinical Research, LLC

Richardson, Texas, United States

Mid Columbia Research

Richland, Washington, United States

Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD

Burgas, , Bulgaria

State Psychiatry Hospital - Kardzhali

Kardzhali, , Bulgaria

State Psychiatry Hospital Sv. Ivan Rilski

Novi Iskar, , Bulgaria

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, , Bulgaria

Mental Health Center - Ruse EOOD

Rousse, , Bulgaria

University Multiprofile Hospital for Active Treatment Alexandrovska EAD

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment - Targovishte AD

Targovishte, , Bulgaria

Mental Health Center - Veliko Tarnovo EOOD

Veliko Tarnovo, , Bulgaria

Mental Health Center - Vratsa EOOD

Vratsa, , Bulgaria

Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej im. Dr. Stanislawa Deresza w Choroszczy

Choroszcz, , Poland

Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Psychiatrii Doroslych

Gdansk, , Poland

NZOZ Centrum Medyczne HCP Sp. z o. o.

Poznan, , Poland

NZOZ Prywatna Klinika Psychiatryczna Inventiva

Tuszyn, , Poland

Clinic for Psychiatric Disorders Dr Laza Lazarevic

Belgrade, , Serbia

Clinical Center of Serbia

Belgrade, , Serbia

Clinical Hospital Center Dr Dragisa Misovic-Dedinje

Belgrade, , Serbia

Special Hospital for Psychiatric Diseases Kovin

Kovin, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center of Vojvodina

Novi Sad, , Serbia

Countries

United States; Bulgaria; Poland; Serbia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

331-201-00080

Identifier Type: -

Identifier Source: org_study_id