An eight-week, multinational, multicenter, double-blind, active- and placebo-controlled clinical trial evaluating the efficacy and tolerability of three fixed doses of SSR125543 (20mg daily, 50 mg daily and 100 mg daily) in outpatients with major depressive disorder.

CRF (corticotripin releasing factor) is a substance produced in a very specific
zone of the brain (the hypothalamus). After CRFbinded at specific receptors
(CRF-receptors), it gives various responses in the organism. CRF is excreted in
case of stress. The purpose of this excretion is coordinate the total of
responses (endrocrine, immune, periferal nervous system, behaviour, ..) to be
ready for a good response.
Extensive literature suggests that the "CRF-circuit" (production, activation of
the receptors,..) unusually active is at affective and anxiety disorders and
that CRF plays a causative role. Additional evidence suggests that particular
CRF receptors, the CRF1 receptors, mediate anxiety and depression-like
behaviours. These data suggest that a CRF1 antagonist may have efficacy in the
treatment of affective and anxiety disorders in man. At the moment, there is no
other medicine with this characterics registered in the indication anxiety or
depressive disorders, but this research domain is very active because they will
expand the therapeutic possibilities for patients.
SSR125543 is in clinical development and is a CRF-type 1 receptor antagonist
(=blocking). Numerous preclinical test with this subtance were performed.
Because the results were promissing, the clinical development was started.
Until this moment only healthy volunteers were admistered with SSR125543 (Fase
I) in order to investigate which doses are the most effective.

The objective of the study is to evaluate various doses of SSR125543 in first
patients (outpatients with a major depressive disorder), evaluate collected
information concerning tolerability, efficacy en safety. The same infomation
will be evaluated for patients who receive placebo or the active comparator
(escitalopram) for which it is proven to be effective in this disorder.

- 1 week "screening" without treatment
- 8 weeks "dubbel-blind" treatment
- 2 weeks follow-up
In total 11 weeks study per patient.

In this study, patients receive one of the following treatments:
- SSR125543 1 capsule at a dose of 20 mg + 1 capsule placebo;
- SSR125543 1 capsule at a dose of 50 mg, + 1 capsule placebo;
- SSR125543 2 capsule at a dose of 50 mg;
- 2 capsules of placebo
- Escitalopram 1 capsule at a dose of 10 mg, + 1 capsule placebo. Escitalopram
(= active substance, class: selective serotonin reuptake inhibitor (SSRI)).

During this 11 week clinical trial, the patient will visit the research site 8
times. The following procedures will be performed:
- 10 x bloodsampling (1 x hepatitis screen, 2 x pregnancy test, 4 x hormone
profile, 6 x monitoring serum cortisol, 6 x standard hematology, biochemistry
and coagulation test)
- 8 x measurement heartrate
- 8 x temperature measurement (oral)
- 1 x measurement lenght
- 2 x measurement weight
- 1 x drug screen
- 2 x pregnancy test (for women only, if applicable)
- 4 x ECG

The following questionnaires will be assessed by the investigator:
1 x DSM-IV/MINI
8 x C-SSRS
8 x HAMD
7 x CGI
3 x MADRS

The following questionnaires will be answered by the patient (self-assessment):
- DESS (Discontinuation-emergent signs and symptoms scale) - from visit 7 to
visit 8, every two days
- SHEEHAN (SHEEHAN disability scale) - 2 x
- ETISR-SF (Early Trauma Inventory Self Report - Short Form) - 2 x
- PHQ-15 (Patient Health Questionnaire-15) - 2 x