E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039638 |
E.1.2 | Term | Schizophrenia, disorganised type |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039639 |
E.1.2 | Term | Schizophrenia, paranoid type |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052792 |
E.1.2 | Term | Schizophrenia, undifferentiated type |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039637 |
E.1.2 | Term | Schizophrenia, catatonic type |
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 assess the effect of zicronapine versus risperidone on metabolic parameters comprising body weight, BMI, waist circumference, levels of fasting blood lipids and glucose during 6 months of treatment |
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E.2.2 | Secondary objectives of the trial |
- to assess the overall safety and tolerability of zicronapine (ZIC) versus risperidone (RIS)
- to assess the potential of ZIC versus RIS to induce EPS
- to assess the effect of ZIC versus RIS on serum prolactin levels
- to assess the effect of ZIC on suicidal ideation and behaviour
- to assess the effect of ZIC versus RIS on ECG
- to assess the efficacy of ZIC versus RIS
- to assess the efficacy of ZIC versus RIS by comparing the proportions of responders
- to assess the efficacy of ZIC versus RIS on global improvement
- to assess the effect of ZIC versus RIS on personal and social functioning
- to assess the effect of ZIC versus RIS on functioning
- to assess the effect of ZIC versus RIS on quality of life
- to assess the effect of ZIC versus RIS on the patient’s satisfaction with treatment
- to assess the PK properties of ZIC and its major metabolite Lu AA22774
- to explore biological parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The patient meets the DSM-IV-TR criteria for schizophrenia (codes 295.10, 295.20, 295.30, 295.90)
- The patient is a man or woman, ≥18 and ≤65 years old
- The patient has a PANSS total score ≥60 and ≤100 at screening and baseline
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E.4 | Principal exclusion criteria |
- The patient has a current Axis I psychiatric disorder other than schizophrenia as defined in the DSM-IV-TR
- The patient has a current diagnosis or a history of substance dependence (except nicotine) or substance abuse (except cannabis) according to the DSM-IV-TR criteria ≤6 months prior to screening
- The patient is at significant risk of harming himself/herself or others according to the investigator’s judgement (assisted by the assessment of suicidal ideation and behaviour using the C-SSRS)
- The patient is resistant to antipsychotic treatment according to the investigator’s judgement or has been treated with clozapine ≤ 3 months prior to screening
- The patient has experienced an acute exacerbation requiring hospitalisation ≤ 3 months prior to screening or between screening and baseline
- The patient has been treated with risperidone or paliperidone ≤6 months prior to screening
- The patient has been treated with an adequate course of risperidone or paliperidone and failed to respond or has shown intolerance to the drug according to the investigator`s judgement |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the effect of zicronapine versus risperidone on metabolic parameters comprising body weight, body mass index (BMI), waist circumference, levels of fasting blood lipids and glucose during 6 months of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation at the end of the study |
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E.5.2 | Secondary end point(s) |
Safety endpoints:
• To assess the overall safety and tolerability of zicronapine versus risperidone during 6 months of treatment
• To assess the potential of zicronapine versus risperidone to induce extrapyramidal symptoms using change from baseline to each assessment in the AIMS, BARS, and SAS total scores
• To assess the effect of zicronapine versus risperidone on serum prolactin levels
• To assess the effect of zicronapine on suicidal ideation and behaviour using the Columbia Suicide-Severity Rating Scale (C-SSRS)
• To assess the effect of zicronapine versus risperidone on electrocardiogram (ECG) parameters
Efficacy endpoints:
• To assess the efficacy of zicronapine versus risperidone following 6 months of treatment using change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score
• To assess the efficacy of zicronapine versus risperidone using change from baseline to each assessment in the PANSS total score and PANSS subscale scores (Positive Symptoms, Negative Symptoms, and General Psychopathology
• To assess the efficacy of zicronapine versus risperidone by comparing the proportions of responders (using two definitions of response: ≥20% and ≥50% decrease from baseline in PANSS total score)
• To assess the efficacy of zicronapine versus risperidone on global improvement using change from baseline to each assessment in the Clinical Global Impression – Severity of Illness (CGI-S) score
• To assess the effect of zicronapine versus risperidone on personal and social functioning using the Personal and Social Performance Scale (PSP)
• To assess the effect of zicronapine versus risperidone on functioning using the Global Assessment of Functioning scale (GAF)
• To assess the effect of zicronapine versus risperidone on quality of life using the disease-specific Schizophrenia Quality of Life scale (S-QoL)
• To assess the effect of zicronapine versus risperidone on the patient’s satisfaction with treatment using the Medication Satisfaction Questionnaire (MSQ)
Other endpoints:
• To assess the pharmacokinetic (PK) properties of zicronapine and its major metabolite Lu AA22774 in patients with schizophrenia
• To explore biological parameters (including gene expression profiling, metabolomics, and genetic biomarker analysis) that may be associated with schizophrenia, the effect of treatment, and/or the treatment response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation at the end of the study |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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 study for an individual patient is defined as the last protocol-specified contact with that patient. The overall end of the study is defined as the last protocol-specified contact with the last patient ongoing in the study. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |