| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | P.T. |
| E.1.2 | Classification code | 10039626 |
|
| 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 |
| The primary objective of this pilot study is to assess the clinical and biological safety of S 33138 after 8 weeks of oral administration in schizophrenic patients with predominant positive symptoms. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- to assess the efficacy of S 33138,
- to get an evaluation of patient’s subjective well-being,
- to assess the pharmacokinetics of S 33138 and S 35424.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Selection criteria :
- Male or female, aged between 18 and 65 years old (inclusive),
- Hospitalised for an acute first episode or a relapse of schizophrenia paranoid or undifferentiated types or provisional schizophreniform disorder or schizoaffective disorder .
- Patients with a total score of at least 60 for the 30-item PANSS, a score of at least 4 on three or more items of the PANSS positive subscale, a (PANSS positive subscale score - PANSS negative subscale score) > 0 and with a CGI severity of illness score of at least 4.
Inclusion criteria :
- Patients with a total score of at least 60 for the 30-item PANSS (scoring 1-7), a score of at least 4 on three or more items of the PANSS positive subscale, a (PANSS positive subscale score - PANSS negative subscale score) >0,
- Patients with a CGI Severity of Illness score of at least 4 (moderately ill),
- Normal results (or judge by the investigator as clinically not significant) for physical examination and vital signs.
|
|
| E.4 | Principal exclusion criteria |
Non-selection criteria - General criteria :
- Pregnant or breast feeding women,
- Women of childbearing potential or women who have been post menopausal for less than 2 years without effective contraception (protected by oral contraception or intra-uterine device or any other method judged by the investigator to be adapted to the patient’s condition),
Non-selection criteria - Medical and therapeutic :
- Patients presenting DSM-IV-TR criteria for any other psychotic disorder such as:
. schizophrenia disorganised type (295.10), catatonic type (295.20) and residual type (295.60),
. delusional disorder (297.1), brief psychotic disorder (298.8), shared psychotic disorder (297.3), substance-induced psychotic disorder and psychotic disorder NOS (298.9),
- Patients with ongoing or previous recurrent disease of the central nervous system, especially convulsive disorders or epilepsy, depression, generalised anxiety disorder, mental retardation, brain tumor, delirium, dementia,
- Patients with a history of not responding to risperidone or who have not responded to risperidone for the present episode,
- Patients having a known hypersensitivity to risperidone,
- Patients with a history of neuroleptic malignant syndrome,
- Patients having received long-acting intramuscular neuroleptic medication or barbiturates within 4 weeks before the selection visit,
- Patients treated with fluoxetine, lithium, valproate, valpromide, carbamazepine, phenytoine within 15 days preceding the selection visit,
- Patients treated with antidepressants other than fluoxetine within six days before the selection visit,
- Patients simultaneously treated with two or more QT/QTc interval prolonging drugs and/or two or more concomitant treatments which are CYP 2D6 substrates or inhibitors, and/or 2C19 and/or 3A4 inhibitors, which cannot be stopped and/or must be maintained during the study,
- Patients resistant to antipsychotic treatment defined as failure to respond to at least 3 periods of treatment lasting at least 6 weeks in the preceding 5 years with antipsychotics from at least 2 different chemical classes at maximum effective dosages (e.g. 300 mg per day of chlorpromazine or 20 mg per day of haloperidol or 8 mg per day of risperidone or 15 mg per day of olanzapine), and with no period of relatively good functioning within the previous 5 years,
- Patients who are non responders for the present psychotic episode defined as failure to respond to at least two different adequate antipsychotic treatments, during 3 weeks at an adequate dose,
- Patients with previous or present history of severe or uncontrolled cardiovascular, pulmonary, infectious, autoimmune, renal, hepatic, gastro-intestinal, ophthalmologic, endocrine, blood disease or cancer,
- Patients with severe or uncontrolled arterial hypertension,
- Patients with a known moderate to severe hepatic or renal insufficiency,
- Patients having a known glucose intolerance or diabetes type I or II,
- Patients with a known lactose intolerance,
- Patients with congestive or ischemic heart disease or infarction,
- Patients with a known personal or family history of Long QT Syndrome,
- Patients with history of extreme and/or repeated violence or judged by the investigator to be at risk of suicide or homicide,
- Patients with presence of alcohol or drug abuse or addiction.
Non-inclusion criteria :
- Patients having significant abnormalities seen with the 12-lead ECG as: QTc > 450 ms, AVBIIb, AVBIII, repeated sequences of 3 or more consecutive VES, or any other disorder judged by the investigator as clinically significant,
- Patients having biological results [haematology, blood biochemistry, endocrinology and urinalysis (glucose, protein, acetone)] out of the normal range and judged by the investigator as clinically significant,
- With positive urinary drug screening: opiates, barbiturates, amphetamines, cocaine (except benzodiazepines and cannabinoids),
- With positive blood alcohol level,
- With positive serology tests (Hbs antigen, anti-HCV antibodies). However, if results are not yet available at the time of the inclusion and if the other hepatic biological results are normal, patients can be included according to investigator's judgement. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The safety criteria are:
- Adverse events,
- Simpson-Angus scale total score,
- Barnes Akathisia scale,
- UKU side effect rating scale ,
- ECG parameters issued from the central reading of ECG tracings,
- ECG abnormalities issued from the central reading of ECG tracings,
- Supine Blood pressure [SBP (mmHg) and DBP (mmHg)] and Heart rate (bpm),
- Body temperature (°C) and Body weight (kg),
- Laboratory parameters.
The efficacy criteria are:
- Positive And Negative Syndrome Scale (PANSS) total score,
- PANSS positive subscale score,
- PANSS negative subscale score,
- PANSS-derived Brief Psychiatric Rating Scale (BPRS) score,
- Clinical Global Impression (CGI) Severity of Illness score, CGI Global Improvement score, CGI Efficacy Index,
- Response to treatment defined as a decrease from baseline > or = 20% of the PANSS total score and a CGI Global Improvement equal to 1 (very much improved) or 2 (much improved),
- Response to treatment defined as a decrease from baseline > or = 30% of the PANSS positive subscale score and a CGI Global Improvement equal to 1 (very much improved) or 2 (much improved).
|
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | 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.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
Print
