Randomized, Placebo-controlled Trial of an AMPAkine in Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to test a candidate drug, Org 24448,in a phase II clinical trial in adult patients with moderately treatment-resistant unipolar major depressive disorder.

Detailed Description
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Major depressive disorder (MDD) is a common, severe, chronic and often life-threatening illness. Major depression contributes to significant morbidity and mortality. Available pharmacotherapies for major depression are suboptimal in terms of speed of onset, efficacy, and tolerability. Current medications for severe, chronic mood disorders are not based on pathophysiological models of illness, but rather are variation of monoaminergic-based therapies. Org 24448 represents a new treatment approach for depression, by potentiating the AMPA receptor subfamily of ionotropic glutamate receptors. This drug has been shown to have antidepressant features in preclinical models, as well as cognitive-enhancing qualities.

Official Title
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Randomized, Placebo-controlled Trial of an AMPAkine in Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: ORG 24448
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical Diagnosis of MDD Have not responded to an adequate trial of one antidepressant in the current episode or have not completed antidepressant trials due to intolerance to ≤3 antidepressant medications in the current or a previous episode Exclusion Criteria: Presence of psychotic features, OCD, drug or alcohol dependency with the preceding 3 months

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Org 24448<br>ampa receptor potentiator for the treatment of MDD | Drug: ORG 24448<br>* flexible regimen starting at 250mg once a day, increasing to maximum of 750mg twice a day.<br>* Other names: AMPA receptor potentiator;|
| Placebo Comparator: Placebo<br>matching placebo pill | Drug: Placebo<br>* matching placebo pill - flexible regimen starting at 250mg once a day, increasing to maximum of 750mg twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to 8 weeks | Reduction of depressive symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at 8 weeks as compared to baseline. | at baseline and at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in neuropsychological function from baseline to 7 weeks | Effect on neuropsychological functioning measured by neuropsychological testing | at baseline and at 7 weeks |