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

Bipolar I Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03259555
• Other study ID #: 331-201-00080
• Status: Completed
• Phase: Phase 3
• Start date: September 14, 2017
• Est. completion date: January 2, 2019

Study information

• Verified date: February 2020
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 322
• Est. completion date: January 2, 2019
• Est. primary completion date: January 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Bipolar Disorder
• Bipolar I Disorder
• Manic Episode

Intervention

Drug:
• 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.
• Placebo
Administered orally daily for 3 weeks.

Locations

Country	Name	City	State
Bulgaria	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	Ruse
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
Poland	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
Serbia	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
United States	Radiant Research Inc.	Atlanta	Georgia
United States	Community Clinical Research, Inc.	Austin	Texas
United States	University of Texas at Austin	Austin	Texas
United States	Carolina Clinical Trials, Inc.	Charleston	South Carolina
United States	ProScience Research Group	Culver City	California
United States	CBH Health	Gaithersburg	Maryland
United States	Collaborative Neuroscience Network, LLC	Garden Grove	California
United States	Pillar Clinical Research, LLC	Garland	Texas
United States	Behavioral Research Specialists, LLC	Glendale	California
United States	Galiz Research	Hialeah	Florida
United States	Alexian Brothers Center for Psychiatric Research	Hoffman Estates	Illinois
United States	Advanced Research Institute of Miami	Homestead	Florida
United States	Florida Behavioral Medicine	Largo	Florida
United States	Woodland International Research Group	Little Rock	Arkansas
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	Pacific Research Partners, LLC	Oakland	California
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	SP Research PLLC	Oklahoma City	Oklahoma
United States	NRC Research Institute	Orange	California
United States	Asclepes Research Centers	Panorama City	California
United States	Richard H Weisler, MD, PA, and Associates	Raleigh	North Carolina
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	Mid Columbia Research	Richland	Washington
United States	Ci Trials	Riverside	California
United States	Woodland Research Northwest, LLC	Rogers	Arkansas
United States	Advanced Clinical Research Center, LLC	Saint Louis	Missouri
United States	Sharp Vista Hospital	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3	The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the "best" rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MMRM).	Baseline, Week 3
Secondary	Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3	The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill.	Baseline, Week 3