| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 17.0 |
| 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 |
| The primary objective of this trial is to assess the effect of asenapine 2.5 and 5 mg twice daily (BID) compared with placebo in the treatment of schizophrenia (overall symptoms) at Day 42 as measured by the Positive and Negative Syndrome Scale (PANSS). |
|
| E.2.2 | Secondary objectives of the trial |
The key secondary efficacy objectives are to evaluate the effectiveness of 2.5 and 5 mg BID asenapine compared with placebo in:
• Clinical Global Impression Severity of Illness (CGI-S)
• Rate of PANSS Responders
The key safety objective is to evaluate weight change associated with asenapine in comparison with olanzapine. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Each subject must be at least 18 years of age and of legal minimum age for signing the consent form.
• Each subject must have a current diagnosis of schizophrenia of paranoid (295.30), disorganized (295.10), or undifferentiated (295.90) subtype.
• Each subject must have a minimum PANSS total score of 70 at Screening and Baseline.
• Each subject must have a score of at least 4 (moderate) in two or more of the five items in the positive subscale of the PANSS (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/persecution) at Screeningand Baseline.
• Each subject must be confirmed (documented in the psychiatric intake evaluation form by the investigator, and reviewed by the sponsor designated medical expert [SDME] prior to randomization) to be experiencing an acute exacerbation of schizophrenia, as evidenced by ALL of the following:
- duration of the current episode is no more than 8 weeks,
- the subject’s current symptoms represent a marked and substantial change compared with the subject’s symptomatic state prior to the emergence of the current episode.
- the subject is in need of increased medical attention to treat worsening positive symptoms
• Each subject must taper off all prohibited psychotropic medications (including antipsychotics, antidepressants, and mood stabilizers) with last dose taken no later than the evening prior to Baseline (the dosing cycle of depot neuroleptics must end no later than the day prior to Baseline). For subjects who skip the tapering period, tapering off must be done, with last dose taken no later than the day of Screening (the dosing cycle of depot neuroleptics must end no later than the day of Screening). |
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| E.4 | Principal exclusion criteria |
A subject must not have a past or current diagnosis of schizoaffective disorder (295.70), schizophrenia of residual subtype (295.60) or schizophrenia of catatonic subtype (295.20) as determined by the investigator and must not have a current diagnosis of schizophrenia with course specifiers
continuous, single episode in partial remission, or single episode in full remission.
• 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.
• A subject must not have a known diagnosis of borderline personality disorder.
• A subject must not currently (within the past 6 months) meet the DSM-IV-TRTM criteria for substance
abuse or dependence (excluding nicotine).
• 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 Columbia Suicide Severity Rating Scale (C-SSRS).
Note that subjects must be excluded at Screening if they report suicidal ideation of Type 4 or 5 (ie, suicidal ideation with intent, with or without a plan) in the past 2 months or suicidal behavior in the past 6 months as measured by the C-SSRS; subjects must be excluded at Baseline if they report suicidal ideation of Type 4 or 5 or suicidal behavior, as measured by the C-SSRS between Screening and Baseline. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this trial is the change from Baseline to Day 42 in the PANSS total score using the Full Analysis Set. The primary efficacy analysis will be performed on the full analysis set population using a mixed model for repeated measures analysis (MMRM). The model will include change from
Baseline in PANSS total score at each visit as the dependent variable, and terms for treatment, center, visit, treatment by visit interaction, and Baseline PANSS total score as covariates. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Baseline to day 42 of treatment |
|
| E.5.2 | Secondary end point(s) |
The key secondary efficacy endpoints are:
1. Change from Baseline to Day 42 in Clinical Global Impression - Severity of Illness Score. The same methodology used for primary endpoint analysis will be performed on this key secondary efficacy endpoint;
2. Rate of responders (≥30% reduction in PANSS total score) at Day 42. Comparisons to the placebo group will be done using a Cochran Mantel-Haenszel test with an adjustment for center. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Baseline to day 42 of treatment |
|
| 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 | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
| Bulgaria |
| Croatia |
| Romania |
| Russian Federation |
| Ukraine |
| United States |
|
| 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
|
| Last patient last visit of 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 30 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 24 |
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