E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of negative symptoms for patients with schizophrenia treated with antipsychotics. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
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 |
• Evaluate efficacy of 24 weeks treatment with RO4917838 in the PANSS
negative symptom factor score in patients with persistent, predominant
negative symptoms of schizophrenia treated with antipsychotics.
• Evaluate safety and tolerability of 24 weeks treatment with
RO4917838 in patients with persistent, predominant negative symptoms
of schizophrenia treated with antipsychotics. |
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E.2.2 | Secondary objectives of the trial |
Evaluate efficacy after 24 weeks of treatment with RO4917838 in
patients with persistent, predominant negative symptoms of
schizophrenia treated with antipsychotics:
• PANSS NSFS in the CFHR1-high subgroup
• personal and social functioning using PSP total score in the all-patient population and in the CFHR1-high subgroup
Additional objectives: evaluate the effect of treatment with RO4917838 in patients with persistent, predominant negative symptoms of schizophrenia, in the all-patient population and the CFHR1 subgroups according to patient's CFHR1 serum at baseline with respect to:
• Other symptom domains of schizophrenia: PANSS total score; PANSS factors: positive symptom, disorganized thought, hostility/excitement, anxiety/depression; PANSS subscales: positive, negative and general psychopathology at week 24;
• Clinical Global Impression of severity and improvement on overall and negative symptoms at week 24; • Safety/tolerability of 52 weeks of randomized study treatment. |
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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 |
AN EXPLORATORY SUBSTUDY TO THE PHASE III STUDIES NN25307 AND NN25310 TO ASSESS THE EFFECTS OF RO4917838 TREATMENT ON BRAIN GLUTAMATE LEVELS AND PREFRONTAL ACTIVATION IN PATIENTS WITH SCHIZOPHRENIA.
Protocol number NN25307 NN25310 MRS fMRI UK Substudy version A dated 5 October 2011.
All objectives of this substudy are exploratory.
Primary Objective
• To explore changes in glutamate levels in the anterior cingulate cortex (measured by proton magnetic resonance spectroscopy [1H-MRS]) that are associated with 12 weeks of
RO4917838/placebo treatment as an adjunct to antipsychotic medication in patients with suboptimally controlled symptoms or predominant negative symptoms of schizophrenia.
Secondary Objectives
• To explore changes in the magnitude of prefrontal activation during verbal fluency performance (measured by functional magnetic resonance imaging [fMRI]) that are associated with 12 weeks of RO4917838/placebo treatment as an adjunct to antipsychotic medication in patients with suboptimally controlled symptoms or predominant negative symptoms of schizophrenia.
• To explore changes in glutamate levels in the thalamus (measured by 1H-MRS) that are associated with 12 weeks of RO4917838/placebo treatment as an adjunct to antipsychotic
medication in patients with suboptimally controlled symptoms or predominant negative symptoms of schizophrenia.
• To explore the associations between:
- the change in glutamate levels in the anterior cingulate cortex and thalamus (measured by 1H-MRS) and the change in the clinical symptoms of schizophrenia that are associated with 12 weeks of RO4917838/placebo treatment as an adjunct to
antipsychotic medication.
- the change in the magnitude of prefrontal activation (measured by verbal fluency fMRI) and the change in the clinical symptoms of schizophrenia that are associated with 12 weeks of RO4917838/placebo treatment as an adjunct to antipsychotic medication.
- the change in glutamate levels in the anterior cingulate cortex and thalamus (measured by 1H-MRS) and the change in the magnitude of prefrontal activation (measured by verbal fluency fMRI) that are associated with 12 weeks of RO4917838/placebo treatment as an adjunct to antipsychotic medication. |
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E.3 | Principal inclusion criteria |
• Adult patients, aged 18 years and above
• Diagnosis of schizophrenia of paranoid, disorganized, residual, undifferentiated or catatonic subtype
• Predominant negative symptoms
• With the exception of clozapine, patients are on any of the available marketed atypical or typical antipsychotics (treatment with a maximum of two antipsychotics) |
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E.4 | Principal exclusion criteria |
• Evidence that patient has clinically significant, uncontrolled and unstable disorder (e.g. cardiovascular, renal, hepatic disorder)
• Patient with Body Mass Index (BMI) <17 kg/m2 or >40 kg/m2
• Depressive symptoms, defined as a score of 9 or greater on the Calgary Depression Rating Scale for Schizophrenia (CDSS)
• A severity score of 3 or greater on the Parkinsonism item of the ESRS-A (Clinical Global Impression, Parkinsonism). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Efficacy (PANSS negative symptoms factor score)
2. Safety (incidence of adverse events) |
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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) |
The key secondary efficacy endpoint is the mean change from baseline in the Personal and Social Performance (PSP) total score. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Quality of Life and Biomarker |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 | 3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Argentina |
Finland |
France |
Hungary |
India |
Korea, Republic of |
Mexico |
Romania |
Russian Federation |
Sweden |
United Kingdom |
United States |
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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 study will end when the last randomized patient completes the last
assessment 4 weeks after the last dose taken. |
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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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |