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

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

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.

Study Overview

• Status: Terminated
• Conditions: Psychosis; Psychotic Depression; Severe Major Depression With Psychotic Features
• Intervention / Treatment: Drug: mifepristone; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, Inc.
    • Little Rock, Arkansas, United States, 72201
      • K&S Professional Research Services, LLC
  • California
    • Anaheim, California, United States, 92804
      • South Coast Clinical Trials, Inc
    • Downey, California, United States, 90241
      • Diligent Clinical Trials
    • Escondido, California, United States, 92025
      • Synergy Clinical Research Center
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Oakland, California, United States, 94612
      • Pacific Research Partners
    • Oceanside, California, United States, 92056
      • North County Clinical Research
    • San Bernardino, California, United States, 92408
      • Breakthrough Clinical Trials
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital
    • San Diego, California, United States, 92126
      • Cnri, Llc
  • Florida
    • Aventura, Florida, United States, 33180
      • Professional Clinical Research, Inc.
    • Gainesville, Florida, United States, 32606
      • University of Florida
    • Hollywood, Florida, United States, 33021
      • Segal Institute for Clinical Research
    • Kissimmee, Florida, United States, 34741
      • Accurate Clinical Trials
    • Miami, Florida, United States, 33144
      • AMB Research Center
    • Orlando, Florida, United States, 32810
      • Lakeside Behavioral Health
    • Tampa, Florida, United States, 33613
      • University of South Florida Dept of Psychiatry and Neurosciences
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Center for Psychiatric Research
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Millennium Psychiatric Associate
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • CRI Lifetree
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
    • Glen Oaks, New York, United States, 11004
      • The Zucker Hillside Hospital
  • North Carolina
    • Hope Mills, North Carolina, United States, 28348
      • Inquest Clinical Group/ Global Research Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19131
      • Belmont Center For Comprehensive Treatment
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC)
  • South Carolina
    • Charleston, South Carolina, United States, 29405
      • Carolina Clinical Trials, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials, L.P.
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75243
      • Pillar Clinical Research, LLC
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research, LLC
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77008
      • Claghorn-Lesem Research Clinic
    • Houston, Texas, United States, 77074
      • Fein-Jennings Clinic, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Publications and helpful links

General Publications

• Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C, Schatzberg AF. An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry. 2002 Sep 1;52(5):386-92. doi: 10.1016/s0006-3223(02)01432-4.
• Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF. Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol. 2001 Oct;21(5):516-21. doi: 10.1097/00004714-200110000-00009.
• Block TS, Kushner H, Kalin N, Nelson C, Belanoff J, Schatzberg A. Combined Analysis of Mifepristone for Psychotic Depression: Plasma Levels Associated With Clinical Response. Biol Psychiatry. 2018 Jul 1;84(1):46-54. doi: 10.1016/j.biopsych.2018.01.008. Epub 2018 Jan 31.
• DeBattista C, Belanoff J, Glass S, Khan A, Horne RL, Blasey C, Carpenter LL, Alva G. Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression. Biol Psychiatry. 2006 Dec 15;60(12):1343-9. doi: 10.1016/j.biopsych.2006.05.034. Epub 2006 Aug 4.
• Flores BH, Kenna H, Keller J, Solvason HB, Schatzberg AF. Clinical and biological effects of mifepristone treatment for psychotic depression. Neuropsychopharmacology. 2006 Mar;31(3):628-36. doi: 10.1038/sj.npp.1300884.

Helpful Links

• Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: March 11, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (ESTIMATE): March 18, 2008

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: psychosis; major depression with psychotic features; psychotic depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Depression; Depressive Disorder; Psychotic Disorders; Mental Disorders; Depressive Disorder, Major; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Abortifacient Agents; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Mifepristone
• Other Study ID Numbers: C-1073-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO