| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Psychotic major depression (major depressive episode, severe, with psychotic features) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037250 |
|
| 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 superiority of adjunctive treatment with 900 mg Org 34517, as compared to placebo, in alleviating psychotic symptoms in patients with psychotic depression on "usual treatment", as measured by the PANSS positive symptoms scale. |
|
| E.2.2 | Secondary objectives of the trial |
- Additional efficacy assessments
- Effects on cognition
- Onset of action, maintenance of effect
- Safety/tolerability
- Population PK
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
a) provide voluntary written informed consent for trial participation after the scope and nature of the investigation have been explained to them, and before starting any trial-related activities (before Screening);
b) be able to speak, read, understand, respond to questions, and follow instructions in English or their native language, if the investigator is fluent in that language and any required documents, including informed consent, can be translated into that language;
c) have a DSM-IV severe depressive episode with psychotic features, as diagnosed by the MINI-Plus for single or recurrent episodes (296.24 or 296.34);
d) have a score on PANSS item “Delusions” AND/OR “Hallucinatory behavior” of at least 4 at Screening and Baseline;
e) have a PANSS Positive Scale score of at least 16 at Screening and Baseline;
f) have a total score of at least 18 on the HAMD 17 item scale at Screening and Baseline;
g) be on a stable dose of usual “treatment”, which has to consist of an antidepressant, an antipsychotic, a mood stabilizer or any combination of these 3 drug classes;
h) be 18 up to and including 70 years of age at Screening;
i) must be willing to be hospitalized for at least 11 days from Screening onwards. Interval between Screening and Baseline is 2 - 3 days and 1 day is needed for confirmation of the diagnosis and subsequent randomization. Subjects will be treated as inpatients for at least 1 week after Randomization. After this period subjects may be treated on an outpatient basis if the investigator is of the opinion that it is safe to do so.
|
|
| E.4 | Principal exclusion criteria |
a) have any other current psychiatric diagnosis (according to the MINI-Plus) except MDD, such as organic mental syndromes and disorders, delirium or anxiety disorders;
b) have a lifetime psychiatric diagnosis of psychotic disorders (according to the MINI), or a MINI diagnosis of past manic episode. Subjects with a MINI diagnosis of past hypomanic episode can be enrolled, provided that their current episode is not hypomanic. Subjects with a MINI diagnosis of panic disorder lifetime can be enrolled, provided that they do not have the MINI diagnosis of panic disorder current;
c) are at significant risk of committing suicide, as indicated by a score greater than 9 on the revised ISST;
d) are currently treated with carbamazepine or valproate;
e) are currently treated with midazolam;
f) have been treated with electroconvulsive therapy (ECT) in the current episode;
g) are currently treated with more than one antidepressant;
h) are currently treated with more than one antipsychotic;
i) are currently treated with more than one mood stabilizer;
j) have “usual treatment” started or discontinued in the 2 weeks before Randomization.
k) have a “usual treatment” dose change within the week prior to Randomization;
l) have any clinically unstable or uncontrollable renal, hepatic, respiratory, hematological, cardiovascular or cerebrovascular disease that would put the patient at risk of safety or bias assessment of efficacy;
m) have known hypersensitivity reactions to glucocorticoid antagonists;
n) have any clinically significant abnormal laboratory data (e.g. aspartate amino transferase (ASAT) and/or alanine amino transferase (ALAT) values > 2x normal range upper limit) or ECG results, or a clinically significant abnormal outcome at the physical examination at the screening visit;
o) have any untreated or uncompensated clinically significant endocrine disorder;
p) have a MINI-Plus diagnosis of alcohol and/or drug dependence;
q) have a confirmed positive result on the drug screening test for any illicit drug, except cannabis, at Screening;
r) are using hormone replacement therapy at Screening;
s) require concomitant treatment with corticosteroids, like dexamethasone, prednisone or cortisol (topical use is allowed);
t) are subjects diagnosed with Cushing’s disease;
u) are women of childbearing potential without adequate contraception (an IUD or oral contraceptives in combination with a barrier method are considered adequate);
v) are women with a positive pregnancy test at Screening or Baseline, or are breastfeeding mothers;
w) Are male subjects with a current diagnosis of prostate hypertrophia or past history (less than 3 months) of symptoms of prostate hypertrophia. Subjects, whose symptoms of prostate hypertrophia were not more recent than 3 months, may be included based on a negative Prostate-Specific Antigen (PSA) test (PSA blood level lower than 4.0 ng/mL) and medical judgment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The PANSS positive symptoms score proportion of 50% responders at both Day 8 and Day 43. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 2 |
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