E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
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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 demonstrate clinically and statistically significant superiority of at least one asenapine dose to placebo in adolescents diagnosed with schizophrenia, as measured by the Positive and Negative Syndrome Scale (PANSS) total score at Day 56. |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Efficacy Trial Objectives: To evaluate the efficacy of asenapine compared with placebo with respect to: • Change from Baseline in the Clinical Global Impression of Severity of subjects’ illness (CGI-S) at Day 56 • The proportion of total PANSS 30% responders (modified definition) at Day 56/endpoint. For other secondary trial objectives see section 6.3 of the protocol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject must fulfill ALL the criteria listed below for entry. 1. Each subject’s parent(s) or legal representative must be willing and able to provide written informed consent for the trial and each subject must indicate assent. Each subject’s parent(s) or legal representative must provide separate written informed consent for pharmacogentic testing and each subject must indicate assent. Subjects whose parent(s) or legal representative are unwilling to provide written informed consent for pharmacogenetic testing, or who do not assent to pharmacogenetic testing, may be included in the trial; however, pharmacogenetic samples must not be obtained. 2. Each subject must be ≥12 years of age when indicating assent to participate in the trial up to <18 years of age when randomly assigned to treatment. A subject may be of either sex, and of any race/ethnicity. 3. Each subject must have a current diagnosis of schizophrenia of paranoid (295.30), disorganized (295.10), or undifferentiated (295.90) subtype, which is confirmed by the K-SADS-PL; 4. Each subject must have a minimum PANSS total score of 80 at Screening and Baseline; 5. Each subject must have a Clinical Global Impressions-Severity (CGI-S) scale score of at least 4 (moderately ill) at Screening and Baseline; 6. Each subject must have a score of at least 4 (moderate) on two or more of the five items in the positive subscale of the PANSS (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/persecution) at Screening and Baseline; 7. Each subject must be a male, or a female who is not of childbearing potential (e.g., surgically sterile) or who is non-pregnant, non-lactating, and is not sexually active or is using a medically accepted method of contraception. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), and hormonal contraceptives. A female subject of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception while receiving protocol specified medication and for 1 month after stopping the medication should she become sexually active while participating in the trial. 8. Each subject must be fluent in the language of the investigator, trial staff (including raters), and the informed consent. 9. Each subject must have a caregiver who is considered reliable by the investigator and who has agreed to provide support to the subject to ensure compliance with trial treatment, outpatient visits, and protocol procedures. The caregiver must be living with the subject and can be the subject’s parent(s) or legal representative. 10. Each subject must have tapered off all prohibited psychotropic medications (including antipsychotics, antidepressants, and mood stabilizers; see section 7.4.2.1 of the protocol) prior to baseline (the dosing cycle of depot neuroleptics must end prior to Baseline). 11. Each subject must agree not to begin formal, structured psychotherapy during treatment during the trial. |
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E.4 | Principal exclusion criteria |
The subject must fulfill ALL the criteria listed below for entry. 1. A subject must not have an uncontrolled, unstable clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy) that may interfere with the interpretation of safety and efficacy evaluations in the opinion of the investigator. 2. A subject must not have a clinically significant abnormal laboratory, vital sign, physical examination, or ECG finding at Screening that, in the investigator’s opinion, precludes the subject’s participation in the trial (potentially interferes with the ability to evaluate safety, tolerability and efficacy of trial medication or potentially impairs the subject’s ability to complete the trial). 3. A female subject must not have a positive serum pregnancy test at Screening, and must not have the intention to become pregnant while receiving protocol-specified medication and for at least one month after stopping the medication. 4. A female subject must not be breast-feeding. 5. A subject must not have uncontrolled or unstable diabetes or a clinically significant abnormal blood glucose level at Screening and Baseline. 6. A subject must not have any known or suspected (non-febrile) seizure disorder. 7. A subject must not have known serological evidence of human immunodeficiency virus (HIV) antibody. 8. A subject must not have a history of neuroleptic malignant syndrome. 9. A subject must not have a history of tardive dyskinesia or tardive dystonia; 10. A subject must not have a diagnosis of schizoaffective disorder (295.70); schizophrenia of residual subtype (295.60); schizophrenia of catatonic subtype (295.20), or schizophrenia with “continuous,” “single episode in partial remission,” or “single episode in full remission” course specifier. 11. A subject must not have a primary Axis I diagnosis other than schizophrenia and must not have a comorbid Axis I diagnosis that is primarily responsible for current symptoms and functional impairment. 12. A subject must not have a known or suspected diagnosis of mental retardation or organic brain disorder. 13. A subject must not have a positive urine drug/alcohol screen finding at the Screening visit, unless the positive finding can be accounted for by documented prescription use. Subjects with positive alcohol, cannabis, or other psychotropic medication results may be included at the investigator's discretion following the guidelines of Section 7.6.1 of the protocol, procedure on urine alcohol/drug screen. 14. A subject must not currently (within the past 6 months) meet the DSM-IV-TR criteria for substance abuse or dependence (excluding nicotine). 15. A subject must not have a diagnosis of psychotic disorder or a behavioral disturbance thought to be substance induced or due to substance abuse. 16. A subject must not be at imminent risk of self-harm or harm to others, in the investigator’s opinion based on clinical interview and responses provided on the C-SSRS. Note that subjects must be excluded if they report suicidal ideation of Type 4 or 5 in the past 2 months or suicidal behavior in the past 6 months as measured by the C-SSRS at Screening or Baseline. 17. A subject must not currently be under involuntary inpatient commitment. 18. A subject must not be unwilling to discontinue or, in the opinion of the investigator, unable to safely taper off any prohibited treatment listed in Table 1 of the protocol prior to the baseline visit without significant destabilization or increased suicidality (see section 7.4.2 of the protocol for details regarding concomitant treatments prior and during the trial). 19. A subject must not have taken clozapine for treatment resistant schizophrenia (ie, at least one other antipsychotic treatments was unsuccessful before clozapine was prescribed as a replacement or as additional medication for the treatment of core symptoms of schizophrenia). 20. A subject must not have used any investigational drugs within 6 months prior to Randomization. 21. A subject must not be participating in any other clinical trial 22. A subject must not have been treated previously in an asenapine trial. 23. A subject, if previously exposed to marketed asenapine, should not be included if the subject was previously non-responsive to asenapine or if the subject was treated with asenapine for the subject’s current episode. 24. A subject must not have been judged by the investigator to be medically non-compliant in the management of their disease. 25. A subject must not be a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial. 26. A subject must not have any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline in PANSS total score at Day 56. |
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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 | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
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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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Last visit/contact of the last subject, according to the protocol |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 31 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 31 |
E.8.9.2 | In all countries concerned by the trial days | 0 |