A clinical study investigating the efficacy, tolerability and safety of brexpiprazole for the acute treatment of manic episodes, with or without mixed features, in subjects with a diagnosis of bipolar I disorder

• Register: EUCTR
• Last refreshed on: 25 August 2020
• Main ID: EUCTR2017-002190-20-HR
• Date of registration: 12/04/2018
• Prospective Registration: No
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: A clinical study investigating the efficacy, tolerability and safety of brexpiprazole for the acute treatment of manic episodes, with or without mixed features, in subjects with a diagnosis of bipolar I disorder
• Scientific 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
• Date of first enrolment: 09/04/2018
• Target sample size: 329
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002190-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Croatia, Romania, Ukraine, United States

Contacts

• Name: Kim Ruppel
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

• Name: Kim Ruppel
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects, ages 18 to 65 years, inclusive, at the time of informed consent.
2. Subjects who are able to complete the consent process as required by IRB or IEC prior to the initiation of any protocol-required procedures.
3. Ability, in the opinion of the principal investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited medication; and to read and understand written word in order to be reliably rated on assessment scales.
4. Subjects with a DSM-5 diagnosis of bipolar I disorder displaying an acute manic episode with or without mixed features requiring hospitalization. Diagnosis confirmed by the 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” is defined as an intervention that occurred rather than one that was recommended.
5. YMRS score of = 24 at screening and baseline.
6. Subjects who, in the investigator’s judgment, require treatment with an atypical antipsychotic medication for their bipolar I disorder.
7. Subjects willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 329
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Sexually active male or WOCBP (women of childbearing potential) who do 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 IMP.
2. Females who are breastfeeding and/or who have a positive pregnancy test result prior to receiving trial medication.
3.Subjects considered unresponsive to clozapine or who are only responsive to cloazapine.
4. Subjects 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, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. All other current diagnoses must be discussed with the medical monitor.
5. Subjects whose current manic episode has lasted for more than 4 weeks overall, or who have required hospitalization > 21 days for the current acute episode at the time of the screening visit, excluding hospitalization for psychosocial reasons.
6. Subject with manic symptoms better accounted for by another general medical condition or direct physiological effect of substance (eg. medication)
7. Subjects who have had electroconvulsive treatment within the past 2 months.
8. Subjects with a positive drug screen for cocaine or other illicit drugs
9. Abnormal laboratory test results, vital signs or ECG results, unless based on investigator's judgment the findings are not medically significant or would not affect the trial results.
10. Rapid cyclers with more than 6 episodes in previous year
11. Subjects with uncontrolled hypo/hyperthyroidism
12. Subjects with uncontrolled hypertension or symptomatic hypotension or orthostatic hypotension.
13. Subject with epilepsy or history of seizures
14. Subjects who participated in a clinical trial within the last 60 days or who participated in more than 2 clinical trials within the past year.
15. Use of psychotropic medications (other than benzodiazepines) within 7 days of the baseline YMRS.
16. Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
17. Subjects who received brexpiprazole in any prior clinical trial or currently taking commercially available brexpiprazole (Rexulti®).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of Manic Episodes Associated with Bipolar I Disorder
MedDRA version: 20.0 Level: LLT Classification code 10068455 Term: Bipolar I disorder, hypomanic System Organ Class: 100000004873

Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Intervention(s)

Trade Name: Rexulti
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Brexpiprazole
CAS Number: 913611-97-9
Current Sponsor code: OPC-34712
Other descriptive name: BREXPIPRAZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Rexulti
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BREXPIPRAZOLE
CAS Number: 913611-97-9
Current Sponsor code: OPC-34712
Other descriptive name: BREXPIPRAZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Rexulti
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BREXPIPRAZOLE
CAS Number: 913611-97-9
Current Sponsor code: OPC-34712
Other descriptive name: BREXPIPRAZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

Secondary Objective: To demonstrate the safety and tolerability of brexpiprazole in this same population.

Primary end point(s): Change from baseline to Day 21 of the double-blind treatment phase in the YMRS Total Score

Timepoint(s) of evaluation of this end point: Baseline to Day 21

Secondary Outcome(s)

Secondary end point(s): The key secondary endpoint is the change from baseline to Day 21 in the double-blind treatment period in Clinical Global Impression – Bipolar (CGI-BP) severity of illness score in mania.
Other secondary efficacy endpoints are as follows:
1. Change from baseline in YMRS Total Score for each trial visit during the double-blind treatment period other than the Day 21 visit; 2. Change from baseline in CGI-BP severity of illness score in mania for each trial visit during the double-blind treatment period other than the Day 21 visit; 3. CGI-BP change from preceding phase score in mania at each trial visit during the double-blind treatment period; 4. YMRS response rate for each trial visit during the double-blind treatment period, where response is defined as = 50% reduction in YMRS Total Score from baseline or YMRS Total Score = 12; 5. YMRS remission rate for each trial visit during the double-blind treatment period, where remission is defined as YMRS Total Score = 12; 6. CGI-BP change from preceding phase response rate in mania for each trial visit during the double-blind treatment period, where response is defined as a CGI-BP change from preceding phase score in mania of 1 or 2 (very much improved or much improved) from baseline

Timepoint(s) of evaluation of this end point: Baseline to Day 21

Secondary ID(s)

NCT03257865

331-201-00081

Source(s) of Monetary Support

Otsuka Pharmaceutical Development &

Ethics review

Status: Approved
Approval date: 20/12/2017
Contact:

Results

• Results available: Yes
• Date Posted: 29/12/2019
• Date Completed: 22/01/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-002190-20/results