E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Negative and depressive symptoms of schizophrenia according to DSM-5 |
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E.1.1.1 | Medical condition in easily understood language |
Negative and depressive symptoms of schizophrenia. Negative symptoms include social withdrawal, avolition, reduced motivation and drive, anhedonia, or depressive mood |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 show that treatment with esketamine is superior over placebo in ameliorating negative and depressive symptoms in patients with schizophrenia, schizophreniform disorder or schizoaffective disorder |
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E.2.2 | Secondary objectives of the trial |
To investigate effects of esketamine treatment on positive symptoms of schizophrenia, schizophreniform disorder or schizoaffective disorder for supporting the claim that esketamine will not lead to psychotic exacerbation in these patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of schizophrenia, other non-affective psychotic disorder, or schizoaffective disorder according to DSM-5 • Minimum score of 60 on the Scale for the Assessment of Negative Symptoms (SANS; Andreasen 1989) or • Minimum score of 22 on the Montgomery and Åsberg Depression Rating Scale (MADRS) (Montgomery and Asberg 1979) • Age of at least 18 years • Ability to provide written informed consent • Female patients of childbearing potential need to utilize a proper method of contraception (pill, vaginal ring, hormonal patch, intrauterine device, cervical cap, condom, contraceptive injection, diaphragm)
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E.4 | Principal exclusion criteria |
• Severe or unstable medical or neurologic disorders or clinically significant abnormality on laboratory screening results • Clinically relevant abnormalities in the electro-cardiogram (ECG) • History of myocardial infarction, angina pectoris, or paroxysmal hypertensive states • Untreated or unstable arterial hypertension • Established diagnosis of advanced arteriosclerosis or hyperthyroidism • Intolerance to Ketanest® or Dibondrin® • Pregnancy or lactation • Current antidepressant treatment (or treatment up to two weeks prior to inclusion) with an irreversible MAO-inhibitor (e.g. tranylcypromine) • Acute suicidal or homicidal ideation • Presence of ferromagnetic metal in the body or heart pacemaker
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change in the Scale for the Assessment of Negative Symptoms (SANS; Andreasen 1982) • Change in Montgomery-Asberg Depression Rating Scale (MADRS; Montgomery & Asberg 1979) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Before initiation of treatment with study drug period 1 (KET/PLC; baseline study period 1) • Six times during treatment with study drug period 1 (KET/PLC; study week 1-2) • Before initiation of treatment with study drug period 2 (KET/PLC; baseline study period 2; study week 4) • Six times during treatment with study drug period 2 (KET/PLC; study week 5-6) • One and two weeks after end of study related treatment (study week 7 and 8)
6 times week 4-5, once week 6, once week 8. |
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E.5.2 | Secondary end point(s) |
• Change in Positive and Negative Syndrome Scale (PANSS; Kay et al. 1987) • Change in Calgary Depression Rating Scale for Schizophrenia (CDSS; Addington et al. 1992) • Clinical Global Impression Scale (CGI; Guy 1976) • Clinician Administered Dissociative States Scale (CADSS; Addinbgton et al. 1992)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Before initiation of treatment with study drug period 1 (KET/PLC; baseline study period 1) • Six times during treatment with study drug period 1 (KET/PLC; study week 1-2) • Before initiation of treatment with study drug period 2 (KET/PLC; baseline study period 2; study week 4) • Six times during treatment with study drug period 2 (KET/PLC; study week 5-6) • One and two weeks after end of study related treatment (study week 7 and 8)
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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 | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |