| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Schizophrenia is a debilitating mental illness. Hallucinations and delusions most characteristic symptoms; however, social withdrawal; lack of emotion, energy and motivation may also be present. |
|
| 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 | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001064 |
| E.1.2 | Term | Acute schizophrenia |
| 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 long-term safety and tolerability of oral OPC-34712 as monotherapy in adults with schizophrenia.
This trial is to be conducted on an outpatient basis. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the long-term efficacy of oral OPC-34712 as monotherapy in adults with schizophrenia. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects who are able to provide written informed consent (as
required by IRB/IEC) prior to the initiation of any protocol-required
procedures.
2. 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 concomitant medication, and to be reliably rated on
assessment scales.
3. Subjects with a current diagnosis of schizophrenia, as defined by
DSM-IV-TR criteria and confirmed by the MINI for Schizophrenia and
Psychotic Disorders Studies, and a history of the illness for at least three
years prior to screening
4. Subjects who are currently being treated with oral antipsychotics
other than clozapine and who, in the opinion of the investigator, require
chronic treatment with antipsychotic medication and could potentially
benefit from monotherapy treatment with oral brexpiprazole for
schizophrenia.
5. Subjects who have been stable on antipsychotic medication or an
antipsychotic regimen for at least one 3-month period in the last year
prior to screening
6. Male and female subjects 18 to 65 years of age
7. Subjects willing to discontinue all prohibited psychotropic medications
to meet protocol-required washouts prior to and during the trial period.
Inclusion Criteria for Rollover Subjects from Trial 331-10-232
8. Subjects who, in the opinion of the investigator, could potentially
benefit from administration of oral brexpiprazole for the treatment of
schizophrenia and who meet one of the following criteria:
- Completed the Double-blind Maintenance Phase (i.e., Week 52 visit) of
Trial 331-10-232
- Met criteria for exacerbation of psychotic symptoms/impending
relapse during the Double-blind Maintenance Phase (Phase C) of Trial
331-10-232 and were withdrawn from the trial
- Was participating in Phase A, B, or C of Trial 331-10-232 at the time of
early trial termination due to a positive result from a planned interim
analysis
- Was participating in Phase A, B or C of Trial 331-10-232 when the trial
reached its conclusion
Inclusion Criteria Assessed Prior to Entry into Phase A
8. Adequate washout of prohibited concomitant medications, including 3
days prior to entry into Phase A for mood stabilizers and antidepressants
9. Subject is receiving antipsychotic(s) other than clozapine. These
subjects must be cross-titrated to brexpiprazole monotherapy over 4
weeks using an initial dose of 1 mg to achieve a recommended target
starting dose in Phase B of 2 mg/day
Inclusion Criteria Assessed Prior to Entry into Phase B
10. Adequate washout of prohibited concomitant medications, including
14 days prior to entry into Phase B for mood stabilizers and
antidepressants
11. Subject is ready to receive oral brexpiprazole as monotherapy for
treatment of schizophrenia.
12. Outpatient status. Subjects hospitalized at the investigator's
discretion during conversion to oral brexpiprazole in Phase A and
hospitalization for psychosocial reasons
|
|
| E.4 | Principal exclusion criteria |
1. Sexually active females of childbearing potential and male subjects
who are not practicing two different methods of birth control with their
partner during the trial and for 30 days
after the last dose of trial medication or who will not remain abstinent
during the trial and for 30 days after the last dose.
2. Females who are breast-feeding and/or who have a positive
pregnancy test result prior to receiving open-label brexpiprazole
3. Subjects with a major protocol violation during the course of their
participation in the double-blind phase 3 trial (ie, Trial 331-10-230, Trial
331-10-231, or Trial 331-10-232).
4. Subjects with schizophrenia who are considered resistant/refractory
to antipsychotic treatment by history or who have a history of failure to
respond to clozapine or response to clozapine treatment only.
5. Subjects with a current DSM-IV-TR Axis I diagnosis other than
schizophrenia including, but not limited to schizoaffective disorder, MDD,
bipolar disorder, post-traumatic stress disorder, anxiety
disorders, delirium, dementia, amnestic or other cognitive disorders.
Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid,
or antisocial personality disorder or mental
retardation.
6. Subjects experiencing acute depressive symptoms within the past 30
days, according to the investigator's opinion, that require treatment with
an antidepressant.
7. Subjects with a significant risk of violent behavior
8. Subjects with clinically significant tardive dyskinesia, as determined
by a score of ≥ 3 on Item 8 of the AIMS at entry
9. Subjects with a score of 5 (severe akathisia) on the BARS global
clinical assessment of akathisia at entry
10. Subjects who have met DSM-IV-TR criteria for substance abuse or
dependence within the past 180 days; including alcohol and
benzodiazepines, but excluding caffeine and nicotine.
11. Subjects with hypothyroidism or hyperthyroidism (unless condition
has been stabilized with medications for at least the past 90 days)
and/or an abnormal result for free T4 at
screening/baseline.
12. Subjects who currently have clinically significant neurological,
hepatic, renal, metabolic, hematological, immunological, cardiovascular,
pulmonary, or gastrointestinal disorders such as any history of
myocardial infarction, congestive heart failure, HIV seropositive
status/acquired immunodeficiency syndrome, or chronic hepatitis B or C.
13. Subjects with IDDM (ie, any subjects using insulin)
14. Subjects with known ischemic heart disease or history of myocardial
infarction, congestive heart failure (whether controlled or uncontrolled),
angioplasty, stenting, or coronary artery bypass
surgery.
15. Subjects with epilepsy or a history of seizures
16. Subjects with uncontrolled hypertension (DBP > 95 mmHg in any
position) or symptomatic hypotension, or orthostatic hypotension which
is defined as a decrease of ≥ 30 mmHg in SBP
and/or a decrease of ≥ 20 mmHg in DBP after at least 3 minutes
standing compared to the previous supine blood pressure, OR
development of symptoms.
17. Subjects who would be likely to require prohibited concomitant
therapy during the trial.
18. Subjects who received ECT within 60 days of the Screening/Baseline
visit for Trial 331-10-237.
19. Subjects who have not received the first dose of IMP in either phase A or B of trial 331-10-232 will not be permitted to enter Trial 331-10-237 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Outcome Measure - safety and tolerability of OPC-34712 to be assessed by examining the frequency and severity of adverse events.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| up to 52 weeks (week 26 for subjects enrolled post - Amendment 2) |
|
| E.5.2 | Secondary end point(s) |
•Change in Positive and Negative Syndrome Scale Positive Subscale, Negative Subscale and Total Scores.
Change in Clinical Global Impression -Severity of Illness scale score
◦Change in Personal and Social Performance scale Total Score
◦Mean Clinical Global Impression - Improvement scale score
◦Improved Response rate
◦Discontinuation rate for lack of efficacy
•Complete Physical Exam, including Clinical Laboratory Tests |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| up to 52 weeks (week 26 for subjects enrolled post - Amendment 2) |
|
| 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 | Yes |
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | 13 |
| 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 |
| Chile |
| Colombia |
| Croatia |
| India |
| Mexico |
| Philippines |
| Russian Federation |
| South Africa |
| Taiwan |
|
| 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
|
| The End of Trial Date is defined as the last Date of Contact or the Date of Final Contact Attempt from the Post-treatment Follow-up eCRF page for the last subject completing or withdrawing from the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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