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

• Sponsor: Corcept Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00637494
• Collaborator: (none)
• Enrollment: 292
• Locations: 42
• Arms: 2
• Duration (Months): 75
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Psychotic Depression; Severe Major Depression With Psychotic Features; Psychosis	Drug: mifepristone; Drug: placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 292 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 [56 days]

   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

Secondary Outcome Measures

1. 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 [56 days]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Corcept Therapeutics

Investigators

• Study Director: Thaddeus Block, MD, Corcept Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Corcept Therapeutics

Publications

• 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.
• 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.
• 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. 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.

• Responsible Party: Corcept Therapeutics
• ClinicalTrials.gov Identifier: NCT00637494
• Other Study ID Numbers: C-1073-14
• First Posted: Mar 18, 2008
• Last Update Posted: Jun 5, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Corcept Therapeutics: psychotic depression; major depression with psychotic features; psychosis
• Additional relevant MeSH terms: Depression; Depressive Disorder; Psychotic Disorders; Mental Disorders; Depressive Disorder, Major; Mifepristone

Study Results

Participant Flow

Arm/Group Title	Mifepristone 1200 mg/Day	Matching Placebo
Arm/Group Description	Mifepristone 1200 mg/day on Days 1-7 and a single-study approved antidepressant on Days 8-56	Matching placebo on Days 1-7 and a single-study approved antidepressant on Days 8-56
Period Title: Overall Study
STARTED	141	151
COMPLETED	109	108
NOT COMPLETED	32	43

Baseline Characteristics

Arm/Group Title	Mifepristone Followed by an Antidepressant	Matching Placebo	Total
Arm/Group Description	Mifepristone 1200 mg/day on Days 1-7 and a single-study approved antidepressant on Days 8-56	Matching placebo on Days 1-7 and a single-study approved antidepressant on Days 8-56	Total of all reporting groups
Overall Participants	141	151	292
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	141 100%	147 97.4%	288 98.6%
>=65 years	0 0%	4 2.6%	4 1.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.4 (9.0)	47.0 (9.5)	46.2 (9.3)
Sex: Female, Male (Count of Participants)
Female	76 53.9%	85 56.3%	161 55.1%
Male	65 46.1%	66 43.7%	131 44.9%
Region of Enrollment (participants) [Number]
United States	141 100%	151 100%	292 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Mifepristone followed by an antidepressant mifepristone: 1200 mg (administered as four 300 mg tablets) once a day by mouth for the initial 7 days	Placebo followed by an antidepressant placebo: Tablets of identical appearance to active drug, once a day by mouth for the initial 7 days
Measure Participants	141	151
Number [participants]	51 36.2%	48 31.8%

2. Secondary Outcome

Title	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
Description	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
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Mifepristone followed by an antidepressant mifepristone: 1200 mg (administered as four 300 mg tablets) once a day by mouth for the initial 7 days	Placebo followed by an antidepressant placebo: Tablets of identical appearance to active drug, once a day by mouth for the initial 7 days
Measure Participants	94	151
Number [participants]	37 26.2%	48 31.8%

Adverse Events

Arm/Group Title	Mifepristone 1200 mg/Day		Matching Placebo
Arm/Group Description	Mifepristone 1200 mg/day on Days 1-7 and a single-study approved antidepressant on Days 8-56		Matching placebo on Days 1-7 and a single-study approved antidepressant on Days 8-56
All Cause Mortality
	Mifepristone 1200 mg/Day		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mifepristone 1200 mg/Day		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/141 (2.1%)		4/151 (2.6%)
Nervous system disorders
Psychotic Disorder	1/141 (0.7%)	1	0/151 (0%)	0
Depression	1/141 (0.7%)	1	2/151 (1.3%)	2
Suicidal Ideation	0/141 (0%)	0	2/151 (1.3%)	2
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/141 (0.7%)	1	0/151 (0%)	0
Other (Not Including Serious) Adverse Events
	Mifepristone 1200 mg/Day		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/141 (81.6%)		103/151 (68.2%)
Gastrointestinal disorders
Nausea	25/141 (17.7%)	35	19/151 (12.6%)	20
Constipation	17/141 (12.1%)	20	14/151 (9.3%)	16
Diarrhoea	11/141 (7.8%)	11	14/151 (9.3%)	15
Dry Mouth	15/141 (10.6%)	15	9/151 (6%)	9
Dyspepsia	14/141 (9.9%)	16	9/151 (6%)	10
Vomiting	11/141 (7.8%)	11	8/151 (5.3%)	8
Abdominal Pain	7/141 (5%)	7	3/151 (2%)	3
Abdominal pain upper	7/141 (5%)	9	3/151 (2%)	3
General disorders
Fatigue	9/141 (6.4%)	16	4/151 (2.6%)	4
Nervous system disorders
Headache	33/141 (23.4%)	41	29/151 (19.2%)	32
Dizziness	11/141 (7.8%)	11	9/151 (6%)	9
Psychiatric disorders
Insomnia	8/141 (5.7%)	9	16/151 (10.6%)	16
Anxiety	8/141 (5.7%)	8	9/151 (6%)	11
Renal and urinary disorders
Pollakiuria	12/141 (8.5%)	15	5/151 (3.3%)	5
Skin and subcutaneous tissue disorders
Rash	9/141 (6.4%)	9	6/151 (4%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.