E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adjunctive treatment of patients with sub-optimally controlled symptoms of schizophrenia. Sub-optimally controlled patients are defined as those who on their current medication have persistent symptoms of psychosis. |
|
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 | 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 |
|
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 the efficacy after 12 weeks of treatment with RO4917838 vs. placebo, as adjunct to antipsychotics, in the PANSS positive symptom factor score in patients with suboptimally controlled symptoms of schizophrenia;
• Evaluate the safety and tolerability after 12 weeks of treatment with RO4917838 vs. placebo as adjunct to antipsychotics, in patients with sub-optimally controlled symptoms of schizophrenia. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate effects of 12
weeks of treatment with RO4917838 vs. placebo in patients with
suboptimally controlled symptoms of schizophrenia treated with
antipsychotics with respect to:
• Symptoms domains of schizophrenia: PANSS total score, PANSS factor
score of negative symptoms, disorganized thought, hostility/excitement,
anxiety/depression; and PANSS syndrome subscale scores of positive,
negative and general psychopathology symptoms at week 12;
• The Clinical Global Impression - Improvement (CGI-I) positive and
overall symptoms with "much" or "very much" improvement at week 12;
• Clinical Global Impression - Severity (CGI-S) on overall and positive
symptoms at week 12;
• Personal and Social Performance (PSP) total score at 12 week;
• Safety and tolerability of 52 weeks randomized study treatment. |
|
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. |
|
E.3 | Principal inclusion criteria |
- Adult patients, >/= 18 years of age
- Diagnosis of schizophrenia
- Clinical stability for the 16 weeks (4 months) prior to randomisation
- Antipsychotic treatment stability for 12 weeks prior to randomisation
- With the exception of clozapine, patients are on any of the available marketed atypical or typical antipsychotic (treatment with a maximum of two antipsychotics) |
|
E.4 | Principal exclusion criteria |
- Has treatment resistant schizophrenia as judged by the treating physician OR have failed two trials
- Evidence that patient has clinically significant uncontrolled or unstable medical disorder (e.g. cardiovascular, renal hepatic, gastrointestinal, hematologic, immunological, neurological, endocrine, metabolic or pulmonary disease)
- Patient with body mass index (BMI) <18.5 kg/m2 or >40 kg/m2
- Diagnosis of mental retardation or severe organic brain syndromes
- In the investigator's judgment, a significant risk of suicide or violent behavior |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Positive symptoms factor score assessed by Positive and Negative
Syndrome Scale (PANSS)
2. Safety (incidence of adverse events) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: Change from baseline to Week 12
2. Time Frame: Week 12 |
|
E.5.2 | Secondary end point(s) |
1. Symptom domains of schizophrenia using Positive and Negative
Syndrome Scale (PANSS)
2. Disease improvement on Clinical Global Impression - Improvement
(CGI-I) symptoms scale
3. Disease severity on Clinical Global Impression - Severity (CGI-S)
symptoms scale
4. Safety (incidence of adverse events) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: Change from baseline to Week 12
2. Time Frame: Change from baseline to Week 12
3. Time Frame: Change from baseline to Week 12
4. Time Frame: Week 52 |
|
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 | Yes |
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 / Biomarkers |
|
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 | 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.8.4.1 | 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 | 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 | Information not present in EudraCT |
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 |
|
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
|
The study will end when the last randomized patient completes the last
assessment 4 weeks after the last dose taken. |
|
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 |