Trial Outcomes & Findings for Novel Therapeutics in Posttraumatic Stress Disorder (PTSD): A Randomized Clinical Trial of Mifepristone (NCT NCT01739335)

NCT ID: NCT01739335

Last Updated: 2018-01-24

Results Overview

A clinical responder at 4-week is defined as a participant who achieves a 30% or greater reduction in CAPS total score (past week symptom status) from baseline to 4-week follow-up. The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. The CAPS total score (ranges 0 - 136) is the sum of 17 PTSD symptoms (each symptom is the sum of the frequency score (ranges 0-4) and the intensity score (ranges 0-4)) in the three different symptom subcategories (intrusive/re-experiencing (0-40), avoidance/numbing (0-56) and hyperarousal (0-40)). The higher is the CAPS total score, the worse is the PTSD symptom. Higher percentage of responders indicate a better drug effect in treating PTSD symptoms.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 81 participants
• Primary outcome timeframe: week 4
• Results posted on: 2018-01-24

Participant Flow

Participant milestones

Measure	Mifepristone (600 mg/Day) 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Overall Study STARTED	41	40
Overall Study COMPLETED	34	35
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Measure	Mifepristone (600 mg/Day) 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Overall Study Lost to Follow-up	7	4
Overall Study Ineligible patient randomized	0	1

Baseline Characteristics

Novel Therapeutics in Posttraumatic Stress Disorder (PTSD): A Randomized Clinical Trial of Mifepristone

Baseline characteristics by cohort

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Total n=80 Participants Total of all reporting groups
Age, Continuous	43 years n=5 Participants	37 years n=7 Participants	40 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	39 Participants n=7 Participants	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	25 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	26 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: week 4

Population: Participants who were included in the modified intent-to-treat (mITT) population and also did not miss 4-week CAPS assessment were analyzed. The mITT population include participants who took at least a single dose of study medication and also met all study eligibility criteria.

A clinical responder at 4-week is defined as a participant who achieves a 30% or greater reduction in CAPS total score (past week symptom status) from baseline to 4-week follow-up. The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. The CAPS total score (ranges 0 - 136) is the sum of 17 PTSD symptoms (each symptom is the sum of the frequency score (ranges 0-4) and the intensity score (ranges 0-4)) in the three different symptom subcategories (intrusive/re-experiencing (0-40), avoidance/numbing (0-56) and hyperarousal (0-40)). The higher is the CAPS total score, the worse is the PTSD symptom. Higher percentage of responders indicate a better drug effect in treating PTSD symptoms.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=39 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=38 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Percentage of Clinical Responders at 4-week Follow-up ≥ 30% Reduction in CAPS Total Score	15 Participants	12 Participants
Percentage of Clinical Responders at 4-week Follow-up < 30% Reduction in CAPS Total Score	24 Participants	26 Participants

SECONDARY outcome

Timeframe: week 12

Population: Participants who were included in the modified intent-to-treat (mITT) population and also did not miss 12-week CAPS assessment were analyzed. The mITT population include participants who took at least a single dose of study medication and also met all study eligibility criteria.

A clinical responder at 12-week is defined as a participant who achieves a 30% or greater reduction in CAPS total score (past week symptom status) from baseline to 12-week follow-up. The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. The CAPS total score (ranges 0 - 136) is the sum of 17 PTSD symptoms (each symptom is the sum of the frequency score (ranges 0-4) and the intensity score (ranges 0-4)) in the three different symptom subcategories (intrusive/re-experiencing (0-40), avoidance/numbing (0-56) and hyperarousal (0-40)). The higher is the CAPS total score, the worse is the PTSD symptom. Higher percentage of responders indicate a better drug effect in treating PTSD symptoms.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=32 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=35 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Percentage of Clinical Responders at 12-week Follow-up (End of Study) ≥ 30% Reduction in CAPS Total Score	10 Participants	14 Participants
Percentage of Clinical Responders at 12-week Follow-up (End of Study) < 30% Reduction in CAPS Total Score	22 Participants	21 Participants

SECONDARY outcome

Timeframe: baseline to 4-week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% Confidence Interval (CI) reported is the least square estimates from the repeated-measures analysis.

The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. The CAPS total score ranges 0 to 136, which is the sum of 17 PTSD symptoms (each symptom is the sum of the frequency score (ranges 0-4) and the intensity score (ranges 0-4)) in the three different symptom subcategories (intrusive/re-experiencing (0-40), avoidance/numbing (0-56) and hyperarousal (0-40)). A higher CAPS total score indicates worse PTSD symptoms. A positive change score indicates an increased CAPS total score (i.e., worse PTSD symptoms) at 4-week (12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in CAPS Total Score From Baseline to 4-week and 12-week Change Score from Baseline to 4-week	-13.96 units on a scale Interval -19.61 to -8.31	-15.83 units on a scale Interval -21.57 to -10.08
Change in CAPS Total Score From Baseline to 4-week and 12-week Change Score from Baseline to 12-week	-15.15 units on a scale Interval -22.34 to -7.96	-18.06 units on a scale Interval -25.16 to -10.96

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 4-Week and 12-Week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. Its intrusive symptom subscale (ranges 0 - 40) is the sum of 5 PTSD symptoms (each ranges 0 - 8) in the intrusive/re-experiencing symptom subcategory. A higher intrusive symptom score indicates worse PTSD symptoms. A positive change score indicates an increased intrusive symptom score (i.e., worse PTSD symptoms) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in CAPS Intrusive Symptom Scores From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-4.27 units on a scale Interval -6.89 to -1.64	-5.49 units on a scale Interval -8.17 to -2.82
Change in CAPS Intrusive Symptom Scores From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-4.77 units on a scale Interval -7.91 to -1.63	-7.78 units on a scale Interval -10.86 to -4.7

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 4-Week and 12-Week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. Its avoidance symptom subscale (ranges 0 - 56) is the sum of 7 PTSD symptoms (each ranges 0 - 8) in the avoidance/emotional numbing symptom subcategory. A higher avoidance symptom score indicates worse PTSD symptoms. A positive change score indicates an increased avoidance symptom score (i.e., worse PTSD symptoms) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

The higher is the avoidance/emotional numbing PTSD subscale score, the worse is the PTSD symptom.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in CAPS Avoidance Symptom Scores From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-6.24 units on a scale Interval -9.24 to -3.24	-6.81 units on a scale Interval -9.86 to -3.76
Change in CAPS Avoidance Symptom Scores From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-6.30 units on a scale Interval -9.99 to -2.6	-6.22 units on a scale Interval -9.87 to -2.57

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 4-Week and 12-Week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

The Clinical Administered PTSD Scale (CAPS) was used to assess the diagnosis of PTSD symptoms. Its hyperarousal symptom subscale (ranges 0 - 40) is the sum of 5 PTSD symptoms (each ranges 0 - 8) in the hyperarousal symptom subcategory. A higher hyperarousal symptom score indicates worse PTSD symptoms. A positive change score indicates an increased hyperarousal symptom score (i.e., worse PTSD symptoms) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in CAPS Hyperarousal Symptom Scores From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-3.35 units on a scale Interval -5.16 to -1.53	-3.49 units on a scale Interval -5.33 to -1.64
Change in CAPS Hyperarousal Symptom Scores From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-3.22 units on a scale Interval -5.37 to -1.08	-4.15 units on a scale Interval -6.24 to -2.05

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 4-Week and 12-Week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

The Beck Depression Inventory (BDI) total score (ranges 0-63) is the sum of 21 items (each item rated on a 4-point scale of 0 to 3) relating to symptoms of depression, cognitions, and physical symptoms. The BDI total score measures the overall severity of depression. The higher the BDI total score, the more severe the depression. A positive change score indicates an increased BDI total score (i.e., more severe depression) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Depression (Measured by the BDI Total Score) From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-3.50 units on a scale Interval -6.2 to -0.79	-4.52 units on a scale Interval -7.29 to -1.75
Change in Depression (Measured by the BDI Total Score) From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-2.25 units on a scale Interval -5.34 to 0.83	-5.07 units on a scale Interval -8.19 to -1.96

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 4-Week and 12-Week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

Stressful life total score (ranges 17-85) is the sum of the severity ratings of the 17 PTSD-related symptoms (each symptom is rated on a 5-point scale of 1=not at all to 5=extremely) over the past week. It evaluates the extent to which responders have been "bothered" by the symptoms of PTSD. The higher stressful life score indicates more stressful life events. A positive change score indicates an increased stressful life total score (i.e., more stressful life events) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Changes in PTSD Symptom Severity (Measured by the Stressful Life Total Score From the PTSD Checklist) From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-6.84 units on a scale Interval -9.9 to -3.78	-8.65 units on a scale Interval -11.8 to -5.49
Changes in PTSD Symptom Severity (Measured by the Stressful Life Total Score From the PTSD Checklist) From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-6.84 units on a scale Interval -10.54 to -3.14	-8.12 units on a scale Interval -11.9 to -4.34

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 4-Week and 12-Week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

The Pittsburgh Sleep Quality Index (PSQI) assesses self-report sleep quality and disturbances. Nineteen individual items generate 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. Each component is scored from 0=better to 3=worse. The sum of the 7 component scores yields the PSQI total score (range 0-21) with a higher score indicating a worse sleep quality. A positive change score indicates an increased PSQI total score (i.e., worse sleep quality) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Sleep Quality (Measured by the PSQI Total Score) From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-1.63 units on a scale Interval -2.67 to -0.59	-1.27 units on a scale Interval -2.34 to -0.21
Change in Sleep Quality (Measured by the PSQI Total Score) From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-0.86 units on a scale Interval -2.1 to 0.4	-2.04 units on a scale Interval -3.29 to -0.79

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4-week and 12-week

Population: Participants in the modified intent-to-treat (mITT) population were analyzed. This includes 80 randomized participants who took at least a single dose of study medication and met all study eligibility criteria. Mean and 95% CI reported is the least square estimates from the repeated-measures analysis.

The State-Trait Anger Expression Inventory (STAXI) total score is the sum of 10 items assessing intensity of anger as an emotional state (State Anger) and the disposition to experience angry feelings as a personality trait (Trait Anger). Each item consists of a 4-point scale (1=not at all, 4=very much) that assess intensity of anger at a particular moment and the frequency of anger experience, expression and control. The STAXI total score ranges from 10 to 40, with a higher score indicating a higher intensity of anger.The sum of the 7 component scores yields the PSQI total score (range 0-21) with a higher score indicating a worse sleep quality. A positive change score indicates an increased STAXI total score (i.e., higher intensity of anger) at 4-week (or 12-week) compared to its baseline value, while a negative change score indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=39 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Anger Level (Measured by the STAXI Total Score) From Baseline to 4-Week and 12-Week Change Score from Baseline to 4-week	-0.61 units on a scale Interval -2.78 to 1.56	-1.83 units on a scale Interval -4.05 to 0.4
Change in Anger Level (Measured by the STAXI Total Score) From Baseline to 4-Week and 12-Week Change Score from Baseline to 12-week	-1.73 units on a scale Interval -3.85 to 0.39	-3.20 units on a scale Interval -5.32 to -1.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 1-week

Population: Participants who were included in the modified intent-to-treat (mITT) population and also did not miss 1-week blood collection on cortisol were analyzed. The mITT population include participants who took at least a single dose of study medication and also met all study eligibility criteria.

Mifepristone will induce acute increase in Cortisol and ACTH levels. Higher Cortisol value indicates higher magnitude of mifepristone's effects on negative feedback inhibition. Cortisol value in placebo group at follow-up visits will remain at the similar level as its baseline magnitude. A positive change value indicates increased cortisol level at 1-week (i.e., higher magnitude on negative feedback inhibition) compared to its baseline value, while a negative change value indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=38 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Plasma Cortisol From Baseline to 1-Week	22.3 ug/dl Interval 3.3 to 33.2	-0.9 ug/dl Interval -3.4 to 3.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4-week

Population: Participants who were included in the modified intent-to-treat (mITT) population and also did not miss 4-week blood collection on cortisol were analyzed. The mITT population include participants who took at least a single dose of study medication and also met all study eligibility criteria.

Mifepristone will induce acute increase in Cortisol and ACTH levels. Higher Cortisol value indicates higher magnitude of mifepristone's effects on negative feedback inhibition. Cortisol value in placebo group at follow-up visits will remain at the similar level as its baseline magnitude. A positive change value indicates an increased cortisol level at 4-week (i.e., higher magnitude on negative feedback inhibition) compared to its baseline value, while a negative change value indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=38 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=35 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Plasma Cortisol From Baseline to 4-Week	-0.6 ug/dl Interval -7.0 to 3.1	-0.4 ug/dl Interval -2.4 to 3.4

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 1-week

Population: Participants who were included in the modified intent-to-treat (mITT) population and also did not miss 1-week blood collection on ACTH were analyzed. The mITT population include participants who took at least a single dose of study medication and also met all study eligibility criteria.

Mifepristone will induce acute increase in Cortisol and ACTH levels. Higher ACTH value indicates higher magnitude of mifepristone's effects on negative feedback inhibition. ACTH value in placebo group at follow-up visits will remain at the similar level as its baseline magnitude. A positive change value indicates an increased ACTH level at 1-week (i.e., higher magnitude on negative feedback inhibition) compared to its baseline value, while a negative change value indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=41 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=38 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Adrenocorticotropic Hormone (ACTH) From Baseline to 1-week	28.8 pg/ml Interval 7.9 to 63.7	-0.5 pg/ml Interval -5.0 to 5.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4-week

Population: Participants who were included in the modified intent-to-treat (mITT) population and also did not miss 4-week blood collection on ACTH were analyzed. The mITT population include participants who took at least a single dose of study medication and also met all study eligibility criteria.

Mifepristone will induce acute increase in Cortisol and ACTH levels. Higher ACTH value indicates higher magnitude of mifepristone's effects on negative feedback inhibition. ACTH value in placebo group at follow-up visits will remain at the similar level as its baseline magnitude. A positive change value indicates an increased ACTH level at 4-week (i.e., higher magnitude on negative feedback inhibition) compared to its baseline value, while a negative change value indicates an opposite direction.

Outcome measures

Measure	Mifepristone (600 mg/Day) n=38 Participants 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=35 Participants Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Change in Adrenocorticotropic Hormone (ACTH) From Baseline to 4-week	-0.8 pg/ml Interval -7.3 to 2.6	1.5 pg/ml Interval -5.5 to 6.2

Adverse Events

Mifepristone (600 mg/Day)

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Mifepristone (600 mg/Day) n=41 participants at risk 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=40 participants at risk Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Social circumstances Social stay hospitalization	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.

Other adverse events

Measure	Mifepristone (600 mg/Day) n=41 participants at risk 600 mg/day mifepristone for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week	Sugar Pill n=40 participants at risk Placebo (sugar pill) for one week Mifepristone (600 mg/day) or placebo (sugar pill): 600 mg/day mifepristone or placebo (sugar pill) for one week
Cardiac disorders Sinus tachycardia	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Endocrine disorders Hyperthyroidism	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Gastrointestinal disorders Abdominal Discomfort	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Gastrointestinal disorders Diarrhea	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Gastrointestinal disorders Dry Mouth	4.9% 2/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Gastrointestinal disorders Gastrointestinal Pain	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Gastrointestinal disorders Nausea	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
General disorders Energy Increased	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
General disorders Fatigue	7.3% 3/41 • Number of events 3 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	5.0% 2/40 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
General disorders Pain	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Injury, poisoning and procedural complications Laceration	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Injury, poisoning and procedural complications Road Traffic Accident	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Investigations Blood thyroid stimulating hormone increase	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Investigations Electrocardiogram Prolonged QT interval	2.4% 1/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	5.0% 2/40 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Investigations Glomerular Filtration Rate Decrease	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Investigations Liver function test increased	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Investigations Platelet Count Decreased	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Investigations Urine analysis abnormal	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Musculoskeletal and connective tissue disorders Tendonitis	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Nervous system disorders Dizziness	4.9% 2/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Nervous system disorders Exertional headache	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Nervous system disorders Headache	4.9% 2/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	7.5% 3/40 • Number of events 3 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Nervous system disorders Somnolence	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Psychiatric disorders Anger	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Psychiatric disorders Depressed Mood	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Contact Dermatitis	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Eczema	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Miliaria	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Pruritis	4.9% 2/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Rash	4.9% 2/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	7.5% 3/40 • Number of events 3 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Skin and subcutaneous tissue disorders Rash pruritic	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Surgical and medical procedures Sympathectomy	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Vascular disorders Hypertension	4.9% 2/41 • Number of events 2 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/41 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	2.5% 1/40 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.
Renal and urinary disorders Nocturia	2.4% 1/41 • Number of events 1 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.	0.00% 0/40 • Participants were enrolled for 3 months. Adverse Events (AE) and Serious Adverse Events (SAE) information were collected from randomization to study medication/placebo until 12 week follow-up and/or participant termination (whichever occurred first). If a participant experienced more than 1 of a given AE, the participant was counted only once for that AE. If a participant experienced more than one AE in a system organ class (SOC), the participant was counted only once in that SOC.

Additional Information

Dr. Julia Golier; Chief of Psychiatry

Bronx VA Medical Center

Phone: 718-584-9000

Email: julia.golier@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place