Psychosis, Psychotic Depression, Severe Major Depression With Psychotic Features
Conditions
Keywords
psychotic depression, major depression with psychotic features, psychosis
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.
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.
Interventions
DRUGmifepristone
1200 mg (administered as four 300 mg tablets) once a day by mouth for the initial 7 days
DRUGplacebo
Tablets of identical appearance to active drug, once a day by mouth for the initial 7 days
Sponsors
Corcept Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mifepristone Followed by an Antidepressant Mifepristone 1200 mg/day on Days 1-7 and a single-study approved antidepressant on Days 8-56 | 141 |
| Matching Placebo Matching placebo on Days 1-7 and a single-study approved antidepressant on Days 8-56 | 151 |
| Total | 292 |
Baseline characteristics
| Characteristic | Matching Placebo | Mifepristone Followed by an Antidepressant | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 147 Participants | 141 Participants | 288 Participants |
| Age, Continuous | 47.0 years STANDARD_DEVIATION 9.5 | 45.4 years STANDARD_DEVIATION 9 | 46.2 years STANDARD_DEVIATION 9.3 |
| Region of Enrollment United States | 151 participants | 141 participants | 292 participants |
| Sex: Female, Male Female | 85 Participants | 76 Participants | 161 Participants |
| Sex: Female, Male Male | 66 Participants | 65 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 115 / 141 | 103 / 151 |
| serious Total, serious adverse events | 3 / 141 | 4 / 151 |
Outcome results
Primary
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
Time frame: 56 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | 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 | 51 participants |
| Placebo | 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 | 48 participants |
Secondary
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
Time frame: 56 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | 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 | 37 participants |
| Placebo | 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 | 48 participants |