E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Schizophrenia ICD-10 code F20 |
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E.1.1.1 | Medical condition in easily understood language |
Schizophrenia which is associated with a distortion in thoughts and perceptions.
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 compare all cause discontinuation rates in patients with schizophrenia randomized to oral antipsychotic medications (i.e., aripiprazole or paliperidone) versus depot antipsychotic medications (i.e., paliperidone palmitate or aripiprazole depot) over an 18 month follow-up period. |
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E.2.2 | Secondary objectives of the trial |
• compare the combined oral medication group with the combined depot treatment arms regarding changes in different dimensions of psychopathology of schizophrenia, global psychosocial functioning, quality of life, resource utilization and safety measures. • compare treatment success regarding the outcomes mentioned above to those achieved in a group of patients who did not agree to participate in the trial but could be followed up with the CGI. • compare side effects and general well-being under antipsychotic medication between the combined oral medication groups with the combined depot treatment arms. • compare the combined oral medication group with the combined depot treatment arms regarding cognitive functioning and aggression incidents.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of schizophrenia as defined by DSM-IV-R as determined by the M.I.N.I.plus 2. Age 18 or older. 3. The first psychosis occurred at least one year and no more than 7 years ago. 4. If patients are using an antipsychotic drug, a medication switch is currently under consideration. 5. Capable of providing written informed consent
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E.4 | Principal exclusion criteria |
1. Intolerance / hypersensitivity to one of the drugs (including active substances, metabolites and excipients) in this study including oral risperidone, paliperidone and aripiprazole. 2. Pregnancy or lactation. 3. Patients who are currently using clozapine. 4. Patients who do not fully comprehend the purpose or are not competent to make a rational decision whether or not to participate. 5. Patients with a documented history of non-response and/or intolerance to any of the study medications. 6. Forensic patients. 7.Patients who have been treated with an investigational drug within 30 days prior to screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to compare all cause discontinuation rates between treatment with the combined oral treatment groups (aripiprazole and paliperidone) to the combined depot treatment groups (aripiprazole depot and paliperidone depot) during 18 months of treatment. This overall measure best reflects effectiveness encompassing in one measurement efficacy, adverse events, and patient’s and physician's attitude towards the drug. Discontinuation consist of : • the allocated treatment is stopped or used at doses outside the allowed range. • medication is switched or augmented with another antipsychotic after visit 4 for more than 1 month continuously or for more than 3 months cumulative over the 18 months of the trial. • a patient misses a monthly visit and does not show up after reminding him (patients who do not show up for appointments will be contacted once). • patient withdraws consent for the study. • clinician decision to withdraw the patient.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Investigators will be encouraged to keep patients in the trial for the full 18 month duration regardless of them meeting discontinuation criteria or not |
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E.5.2 | Secondary end point(s) |
Although the trial is only powered for the primary objective, a number of secondary objectives will be considered and investigated: • comparing the combined oral medication group with the combined depot treatment arms regarding changes in different dimensions of psychopathology of schizophrenia, global psychosocial functioning, quality of life, resource utilization and safety measures. • comparing treatment success regarding the outcomes mentioned above to those achieved in a group of patients who did not agree to participate in the trial but could be followed up with the CGI. • comparing side effects and general wellbeing under antipsychotic medication between the combined oral medication groups with the combined depot treatment arms. • comparing the combined oral medication group with the combined depot treatment arms regarding cognitive functioning. • associations between immune parameters on the one hand, and primary as well as secondary outcome measures on the other. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Investigators will be encouraged to keep patients in the trial for the full 18 month duration regardless of them meeting discontinuation criteria or not. |
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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 | 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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Belgium |
Bulgaria |
Czech Republic |
Denmark |
Germany |
Greece |
Hungary |
Israel |
Italy |
Netherlands |
Norway |
Poland |
Romania |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the trial is 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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |