A Study of Mifepristone vs. Placebo in the Treatment of Patients With Major Depression With Psychotic Features

Study Overview
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Brief Summary
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Approximately 450 patients will be randomized to receive mifepristone or placebo for 7 days followed by antidepressant. The purpose is to compare the efficacy of mifepristone followed by antidepressant versus placebo followed by antidepressant in reducing psychotic symptoms in patients with a diagnosis of psychotic depression.

Detailed Description
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Up to 450 patients with psychotic depression will be randomly assigned to receive either mifepristone or matching placebo. Patients will be assessed by the investigator or site staff during screening and on study days. A single antidepressant selected from a list of approved drugs will be administered after the administration of investigational drug. Adverse events, laboratory assessments, electrocardiograms, and physical examinations will be used to assess safety.

Official Title
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A Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Mifepristone vs. Placebo in the Treatment of Psychotic Symptoms in Patients With Major Depressive Disorder With Psychotic Features

Conditions
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Psychotic Depression, Severe Major Depression With Psychotic Features, Psychosis

Intervention / Treatment
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* Drug: mifepristone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have provided written consent to participate in the study prior to any study procedures and understand that they are free to withdraw from the study at any time. Patients must be able to read and understand the consent form, complete study-related procedures, and communicate with the study staff Have a DSM-IV TR diagnosis of Major Depressive Disorder with Psychotic Features (DSM-IV 296.24 or 296.34), and are clinically symptomatic with their illness Have pre-specified minimum scores on standardized psychiatric rating scales at baseline Have not been taking excluded medication for at least 7 days prior to randomization Have a negative pregnancy test If not postmenopausal for ≥ 2 years or surgically sterile (6 months post-surgery), must consent (patient or partner) to utilize two medically acceptable methods of contraception, one of which is a barrier method, throughout the entire study period and for 3 months after the study is completed Exclusion Criteria: Have any primary psychiatric diagnosis other than psychotic depression. Have a major medical problem, which in the opinion of the investigator would place the patient at undue risk. Have undergone electroconvulsive therapy within 3 months prior to randomization Have had a hospitalization due to a suicide attempt within 45 days prior to randomization Are female and of childbearing age, and are unable or unwilling to use two medically acceptable methods of contraception during the study and for three months after study completion, one of which must be a barrier method Are female and are pregnant or lactating Are currently taking excluded medications Have used drugs of abuse within 30 days prior to screen, as per patient report and urine drug screen Have a history of active drug or alcohol abuse within 3 months or dependence within 6 months prior to screening Are in the opinion of the investigator at immediate risk of suicide, or at risk of harming others Have received investigational therapy (drug, vaccine, biological agent or device) within 6 months prior to randomization Have previously participated in a clinical trial of mifepristone Have a history of an allergic reaction to mifepristone Are in the investigator's opinion not appropriate for participation in the study or may not be capable of following the study schedule for any reason Are patients who are employees of the study unit or their family members, students who are working in the study unit, or family members of the investigator or Corcept Therapeutics

Ages Eligible for Study
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Minimum Age: 22 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Mifepristone followed by an antidepressant | Drug: mifepristone<br>* 1200 mg (administered as four 300 mg tablets) once a day by mouth for the initial 7 days<br>* Other names: Korlym;|
| Placebo Comparator: 2<br>Placebo followed by an antidepressant | Drug: placebo<br>* Tablets of identical appearance to active drug, once a day by mouth for the initial 7 days<br>* Other names: control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Mifepristone vs. Placebo Treated Patients With at Least a 50% Reduction From Baseline in Brief Psychiatric Rating Scale-Positive Symptom Subscale (BPRS-PSS) at Days 7 and 56 | Response as measured by 50% reduction in psychosis at Days 7 and 56 was compared between the group administered placebo and the group administered mifepristone | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Mifepristone Treated Patients With Plasma Drug Concentrations Equal to or Above 1637 ng/mL vs. Placebo Treated Patients Who Achieve a ≤ 50% Reduction in BPRS-PSS at Days 7 and 56 | Response as measured by 50% reduction in psychosis at Days 7 and 56 was compared between the group administered placebo and the group who achieved a sufficiently high plasma level of mifepristone | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psychotic depression, major depression with psychotic features, psychosis