| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Predominant Negative Symptoms of Schizophrenia |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with Predominant Negative Symptoms of Schizophrenia |
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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 | 16.1 |
| 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 |
| To evaluate the efficacy, safety and tolerability of cariprazine for the treatment of patients with schizophrenia having predominant negative symptoms. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- The patient is able to understand the patient information sheet.
- Prior to any screening procedures, the patient must have signed the informed consent form.
- Men and women, aged between 18-65 years (extremes included), suffering from schizophrenia (DSM-IV-TR diagnosis, all subtypes allowed).
- The onset of schizophrenia has been known for at least 2 years prior to the Screening Visit.
- The patient should be known by the investigator, either directly or via another psychiatrist from the site or via a referring psychiatrist. Reliable source data including detailed history of the patient‘s diagnosis of schizophrenia for at least a period of one year prior to the Screening Visit must be available to the investigator.
- Predominant negative symptoms present for at least 6 months at the Screening Visit, based on the medical records and the judgment of the investigator.
- A Positive and Negative Syndrome Scale (PANSS) factor score for negative symptoms 24.
- A score of > or = 4 on a minimum 2 of the 3 PANSS items
o Flat affect (N1 – Blunted affect),
o Avolition (N4 – Passive/apathetic social withdrawal),
o Poverty of speech (N6 – Lack of spontaneity and flow of conversation).
- Female patients of non-childbearing potential or non-pregnant, not breast-feeding women of childbearing potential, using adequate contraception.
- If the patients are treated with antipsychotic medication(s) at the Screening Visit, and
o they must receive one or a maximum of 2 different antipsychotic medication(s);
o the dosage of the antipsychotic medication(s) must not be higher than 6 mg risperidone equivalent daily if the patient is treated with one antipsychotic, or the sum of the dosages of the antipsychotic medications must not be higher than 8 mg risperidone equivalent daily if the patient is treated with 2 antipsychotic medications (Simpson GM et al., 2006);
o the antipsychotic medication(s) must not have been changed within 30 days before the Screening Visit. Dosage(s) may be changed, but not the medication(s). |
|
| E.4 | Principal exclusion criteria |
•Current DSM-IV-TR–based primary diagnosis of mental retardation or an axis I disorder, other than schizophrenia.
•Other psychiatric, neurological, or behavioural disorders that may interfere with the conduct or interpretation of the study.
•The condition of the patient is unstable:
oHospital admission for, or history of acute exacerbation of schizophrenia within 6 months prior to the Screening Visit, based on the medical records, or during the 4-week Prospective Lead-in Period.
oMajor increase in psychiatric care or imprisonment within the last 6 months prior to the Screening Visit, based on the medical record, or during the 4-week Prospective Lead-in Period.
o A PANSS factor score for positive symptoms >19.
oin order to avoid pseudospecificity a score of ≥4 on more than 2 of the following PANSS items: P1 – delusions, P3 – hallucinatory behaviour, P5 – grandiosity, P6 – suspiciousness, G9 – unusual thought content.
oTreatment with clozapine in the 12 months prior to Screening Visit; except episodic use of clozapine at doses ≤ 100 mg/day for the treatment of sleep disorder.
•Substance abuse or dependence (other than nicotine or caffeine) within the prior 12 months.
•Presence of moderate to severe depressive symptoms, defined by the Calgary Depression Scale for Schizophrenia (CDSS) total score >6.
•The patient has clinically relevant parkinsonian symptoms (EPS) as judged by the investigator and/or clinically significant parkinsonian symptoms as evaluated by the sum of the first 8 items on the SAS > 3.
•Treatment with antidepressant medications within 3 months prior to the screening visit.
•Being at significant risk of suicide defined as, in the 12 months prior to Screening, significant risk of suicide according to the investigator judgment, based upon all available source of information including those collected in the C-SSRS; and/or within the 5 years prior to Screening, more than one life-threatening suicide attempt.
•Known or suspected cluster B personality disorders (borderline, antisocial, histrionic and narcissi personality disorders).
•Violent behaviour in the 12 months prior to Screening, according to the investigator’s judgment and/or on PSP scale “Domain d. – Disturbing and agressive behaviors” scored as “Marked”, “Severe” or “Very severe” at Screening Visit.
•Treatment with risperidone within 6 weeks of the Screening Visit.
•History of non-response of a psychotic episode to an adequate trial of risperidone treatment.
•Single episode of schizophrenia without residual symptoms (DSM-IV TR criteria).
• Patients with known history of cataracts, or whose anterior chamber angles are too shallow for safe dilation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline (CFB) to endpoint (Week 26) in the PANSS factor score for negative symptoms |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
CFB to endpoint (Week 26) in Personal and Social Performance (PSP) score
CFB in PANSS negative subscale score at Week 26
CFB on CGI-S at Week 26
CFB in PANSS total score at Week 26
CFB in PANSS general psychopathology scale at Week 26
CGI-I score at Week 26
Responder rates based on number of patients who achieve a decrease of at least 20% in baseline PANSS factor score for negative symptoms |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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) | 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 | No |
| 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 | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| 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 |
| France |
| Croatia |
| Romania |
| Czech Republic |
| Germany |
| Hungary |
| Spain |
| Poland |
| Russian Federation |
| Serbia |
| Ukraine |
|
| 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
|
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
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