E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with schizophrenia on stable antispychotic treatment |
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E.1.1.1 | Medical condition in easily understood language |
patients with schizophrenia who are in the residual (non-acute) phase
and on stable antipsychotic treatment |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039634 |
E.1.2 | Term | Schizophrenia residual |
E.1.2 | System Organ Class | 100000004873 |
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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 provide proof of concept (PoC) and dose finding data in patients with schizophrenia on stable antipsychotic treatment who are treated with oral once daily administration of BI 425809 or placebo |
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E.2.2 | Secondary objectives of the trial |
to assess the safety and pharmacokinetics of BI 425809 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Biomarker sub-study I: MRI brain imaging
Protocol Date: 24-FEB-16
Protocol Version: 1
Biomarker Sub-study II: EEG
Protocol Date: 24-FEB-16
Protocol Version: 1 |
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E.3 | Principal inclusion criteria |
- Men or women who are 18-50 years (inclusive) of age at time of consent
- Established schizophrenia with the following clinical features:
a) Outpatient, with no hospitalization for worsening of schizophrenia within 3 months prior to randomisation
b) Medically stable over the prior 4 weeks and psychiatrically stable without symptom exacerbation within 3 months prior to randomisation
c) patients who have no more than a moderate severe rating on the PANSS positive items P1, P3-P7 and no more than a moderate rating on the PANSS positive item P2
- Current antipsychotic and concomitant psychotropic medications as assessed at Visit 1 must meet the criteria below:
a) patients may have up to 2 antipsychotics (typical and/or atypical)
b) patients must be maintained on current typical and/or atypical antipsychotics other than Clozapine and on current dose for at least 4 weeks prior to randomisation and/or maintained on current long acting injectable antipsychotics and current dose for at least 3 months prior to randomization
c) patients must be maintained on current concomitant psychotropic medications, anticholinergics, antiepilectics and/or lithium for at least 3 months prior to randomisation and on current dose for at least 4 weeks prior to randomisation
- Women of child-bearing potential must be ready and able to use highly effective
methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly.
- Patients must exhibit reliability, physiologic capability, and an educational level sufficient to comply with all protocol procedures, in the investigator´s opinion
- Patients must have an identified informant who will be consistent throughout the study.
-Further inclusion criteria apply |
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E.4 | Principal exclusion criteria |
- Patients who have a categorical diagnosis of another current major psychiatric disorder
- Diseases of the central nervous system that may impact cognitive test performance
- movement disorder not currently controlled
- Patients receiving another investigational drug or procedure within 30 days or 6 half-lives (whichever is longer) or recent participation in another trial with any cognitive enhancing therapy
- recent participation in formal cognitive remediation program
- recent electroconvulsive therapy
- Patients who have been on BI 409306, encenicline or other investigational drug testing effects on cognition in schizophrenia within the last 6 months prior to randomisation or who have previously been on bitopertin
- Participation in a clinical trial with repeated MATRICS Consensus Cognitive Battery (MCCB) assessments within the last 6 months
- Patients who required change in benzodiazepine or sleep medication regimen within the last 4 weeks prior to randomisation
- Treatment with Clozapine within 6 months prior to randomisation
- Treatment with medical devices (e.g. Transcranial Magnetic Stimulation (TMS), neurofeedback) for any psychiatric condition within the last 3 months prior to randomisation
- Patients taking strong or moderate Cytochrome P450 (CYPA4) inhibitors or inducers within the last 30 days prior to randomization
- Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior) prior to randomisation
- Any suicidal ideation of type 4 or 5 in the Columbia Suicidal Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent) prior to randomisation
- Known history of Human Immunodeficiency Virus (HIV) infection, Hepatitis B or C infection
- Hemoglobin less than 130 g/L (13g/dL) in men or 120g/L (12g/dL) in women
-History of hemoglobinopathy such as thalassemia major or sickle-cell anemia
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial or men who are able to father a child, unwilling to be abstinent or use adequate contraception for the duration of the study participation and for at least 28 days after treatment has ended
- Significant history of drug abuse disorder (including alcohol) within the last 6 months prior to informed consent or a positive urine drug screen at screening
- Further exclusion criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: Change from baseline in cognitive function as measured by the composite MATRICS Consensus Cognitive Battery (MCCB) score after 12 weeks of treatment
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1: Change from baseline in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) total score after 12 weeks of treatment
2: Percentage of patients with (Serious)Adverse Evetns (including clinically relevant abnormalities of physical examination, vital signs, Electrocardiogram (ECG) test and laboratory tests)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Austria |
Canada |
Germany |
Italy |
Japan |
Korea, Republic of |
Poland |
Spain |
Taiwan |
United Kingdom |
United States |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 10 |