E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
measure of overall cognitive functioning in chronic schizophrenia |
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MedDRA Classification |
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 neurocognitive effects of amisulpride with those of risperidone in patients with chronic schrizophrenia, as assessed by the general cognitive index, a measure of overall cognitive functioning in schrizophrenia |
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E.2.2 | Secondary objectives of the trial |
Secondary analyses: how the two atypical agents’ neurocognitive effects compare with regard to their profile of therapeutic action; Investigate whether amisulpride elicits more improvement on negative symptoms compared to risperidone treatment, as measured by the total score on the SANS 8 and by the Negative Symptom Subscale of the PANSS; Assess whether amisulpride improves overall functioning and individual domains of psychotic symptoms compared to risperidone as measured by the Clinical Global Impression (CGI), and the total and positive and general psychopathology subscale scores of PANSS and by the individual domains of SANS, respectively; Evaluate the safety and tolerability of amisulpride and risperidone based on the study completion rates, and frequency of abnormal laboratory values, prolactin serum concentrations and on the Simpson Angus Scale for Extrapyramidal Symptoms (SAS) 10 and the Abnormal Involuntary Movement Scale (AIMS).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis: DSM-IV schizophrenia (any subtype) 2. Aged between 18 and 65 years 3. Sex: Male, or non pregnant female subjects 4. General Health: Satisfactory medical assessment with no clinically significant and relevant abnormalities 5. Duration of illness: ≥ 5 years 6. Concomitant standing or prn medications (except other antipsychotics and those contraindicated in the respective package inserts [amisulpride or risperidone]) are permitted during treatment phase, if they were present at a stable dose for at least 6 weeks prior to the start of initial treatment with study medication 7. Overall symptom severity: patients must evidence a total score of 60 or higher on the PANSS scale 8. Clinical Symptoms: A score of 4 (moderate) or greater on any of the 7 items of the PANSS Positive Symptom Subscale (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility) is present 9. Cognitive status (minimum performance level): subject must be able to validly complete the baseline MATRICS assessment (validity of performance to be assessed by Chief Neuropsychologist or NP tester) 10. Clinical judgment by the investigator that treatments with amisulpride or risperidone are warranted due to suboptimal clinical outcome despite previous treatments 11. Patient is judged capable of understanding all relevant risks and potential benefits of the study and provides informed consent
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E.4 | Principal exclusion criteria |
1. Past or current intolerance of amisulpride or risperidone side effects that are judged by the investigator to be unsafe, dose-limiting, or likely to result in study discontinuation. 2. Any contraindication for amisulpride or risperidone therapy as indicated in the drug description. (Contrainidications for amisulpride therapy: prolactine dependent tumours, phaeochromocytome, pregnant or breast feeding woman, creatinine-clearance<10 ml/min, combination with drugs are potential triggers for torsades de pointes and hypersensitivity / intolerance to the active substance or to any of the excipients. Contraindications for risperidone therapy: hypersensitivity / intolerance to the active substance or to any of the excipients.) 3. Presence of any unstable or untreated medical disorder. 4. Any history of seizures or seizure disorder other than febrile seizures of childhood; 5. History of positive hepatitis B surface antigen. 6. Any abnormal laboratory test that is judged to be clinically significant by the investigator. 7. A history of significant head injury/trauma, as defined by: A. loss of consciousness (LOC) for more than 1 hour B. recurring seizures resulting from the head injury C. clear cognitive sequelae of the injury D. cognitive rehabilitation following the injury 8. Alcohol or substance dependence within the past 12 months or abuse within the past 3 months. Any subject with positive urine toxicology or alcohol use that is considered abnormal at baseline. 9. Clinically significant suicidal or homicidal behavior or attempts within past 6 months. 10. Any subject who is judged by the investigator to present a danger to self or others. 11. Any subject who is judged by the investigator to be unable or unlikely to comply with all study requirements, including adherence with prescribed medication regimen. 12. Pregnant or breast-feeding women (excluded by pregnancy test) 13. Absence of medically approved contraceptive methods for female of childbearing potential.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary General cognitive index, as assessed by the overall average z-score based on the neurocognitive test (MATRICS) battery.
Secondary Cognitive measures: Individual subscales scores in seven cognitive domains including speed of processing, attention/vigilance, working memory (verbal and nonverbal), verbal learning and memory, visual learning and memory, reasoning and problem solving and social cognition.
Overall Clinical Effects: Clinical Global Impression (CGI).
Clinical Symptoms/Ratings of psychopathology: The total and each of the subscale scores on the PANSS (positive and negative symptoms, general psychopathology), and the SANS (Attention; Affect; Alogia, asociality/Anhedonia; Avolition).
Ratings of potential side effects: The total, subscale and item scores on the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale, respectively.
General Safety/Tolerability: Completion rates and specific reasons for discontinuation, changes in vital signs, treatment-emergent adverse events, and frequency of abnormal laboratory measures. Prolactin serum concentrations.
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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) | 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 | 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) | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |