| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of Manic Episodes Associated with Bipolar I Disorder |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068455 |
| E.1.2 | Term | Bipolar I disorder, hypomanic |
| E.1.2 | System Organ Class | 100000004873 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the safety and tolerability of brexpiprazole in the treatment of subjects with bipolar I disoder |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- De Novo Subjects :
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 and/or consent obtained from a legally acceptable representative (as required by IRB/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; 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 who do not have severity of bipolar symptoms that, in the opinion of the investigator, would require 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. Subjects who, in the investigator’s judgment, require treatment with an antipsychotic medication for their bipolar I disorder.
6. Subjects willing to discontinue all prohibited medications to meet protocol-required washouts prior
to and during the trial period.
7. Outpatient status. Subjects hospitalized at the investigator’s discretion during conversion to oral
brexpiprazole (OPC-34712) in Phase A and hospitalization for psychosocial reasons (eg, homelessness or need for shelter that is unrelated to the subject’s underlying psychiatric condition) will be considered outpatient status for the purpose of enrollment in Trial 331-201-00083. Subjects hospitalized during the conversion phase (Phase A) must be outpatient at the baseline of Phase B.
Rollover Subjects from Trial 331-201-00080 or 331-201-00081
8. Subjects remaining in hospital at the Day 21 (Week 3) visit of Trial 331-201-00080 or Trial 331- 201-00081 (for other than psychosocial reasons) will be permitted to enroll in Trial 331-201-00083 at the Week 3 visit of the double-blind trial if they are planned to be discharged from the hospital before the Week 1 visit of Trial 331-201-00083. Subjects not discharged by the Week 1 visit of
Trial 331-201-00083 must be withdrawn.
9. Subjects who, in the opinion of the investigator, could potentially benefit from administration of
oral brexpiprazole for the treatment of bipolar I disorder and who completed 3 weeks of post-randomization treatment in Trial 331-201-00080 or Trial 331-201-00081
- Rollover Subjects from Trial 331-201-00080 or 331-201-00081
8. Subjects remaining in hospital at the Day 21 (Week 3) visit of Trial 331-201-00080 or Trial 331-201-00081 (for other than psychosocial reasons) will be permitted to enroll in Trial 331-201-00083 at the Week 3 visit of the double-blind trial if they are planned to be discharged from the hospital before the Week 1 visit of Trial 331-201-00083. Subjects not discharged by the Week 1 visit of
Trial 331-201-00083 must be withdrawn.
9. Subjects who, in the opinion of the investigator, could potentially benefit from administration of oral brexpiprazole for the treatment of bipolar I disorder and who completed 3 weeks of post-randomization treatment in Trial 331-201-00080 or Trial 331-201-00081 |
|
| E.4 | Principal exclusion criteria |
-De Novo Subjects
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®).
- Rollover Subjects from Trial 331-201-00080 or 331-201-00081
18. Subjects with a major protocol violation during the course of their participation in the double-blind
phase 3 trial (ie, Trial 331-201-00080 or 331-201-00081). Minor violations such as occasional visits outside of the acceptable window or a missing blood draw will not exclude a subject from participation in Trial 331-201-00083; however, continual lack of compliance with the visit schedule, trial assessments, or treatment regimen in the prior double-blind trial would be considered a major violation that would result in exclusion from Trial 331-201-00083. The medical monitor should be contacted if the investigator is unsure of a subject’s eligibility. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the safety and tolerability of brexpiprazole (OPC-34712), as assessed by the frequency and severity of adverse events (AEs). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Baseline to 26 weeks or early termination with a 21 day follow-up period |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Croatia |
| Poland |
| Romania |
| Serbia |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 7 |
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