Trial Outcomes & Findings for Exploring the Effects of Corticosteroids on the Human Hippocampus (NCT NCT03896659)

NCT ID: NCT03896659

Last Updated: 2025-12-16

Results Overview

High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

66 participants

Primary outcome timeframe

3 days

Results posted on

2025-12-16

Participant Flow

Study participants included healthy controls and adults with depression being treated at UT Southwestern Medical Center.

Participant milestones

Participant milestones
Measure	Depressed: Hydrocortisone, Then Placebo Participants in the "Depressed' arm first received Hydrocortisone 160 mg tablet every day for 3 days. After a washout period of 25 days, they then received a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.	Depressed: Placebo, Then Hydrocortisone Participants in the "Depressed' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days. After a washout period of 25 days, they then received Hydrocortisone 160 mg tablet every day for 3 days.	Healthy Controls: Hydrocortisone, Then Placebo Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days. After a washout period of 25 days, they then received a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.	Healthy Controls: Placebo, Then Hydrocortisone Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days. After a washout period of 25 days, they then received Hydrocortisone 160 mg tablet every day for 3 days.
First Intervention (3 Days) STARTED	12	11	22	21
First Intervention (3 Days) COMPLETED	12	9	20	21
First Intervention (3 Days) NOT COMPLETED	0	2	2	0
Washout (25 Days) STARTED	12	9	20	21
Washout (25 Days) COMPLETED	10	7	16	20
Washout (25 Days) NOT COMPLETED	2	2	4	1
Second Intervention (3 Days) STARTED	10	7	16	20
Second Intervention (3 Days) COMPLETED	8	7	16	19
Second Intervention (3 Days) NOT COMPLETED	2	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exploring the Effects of Corticosteroids on the Human Hippocampus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Depressed: Hydrocortisone, Then Placebo n=12 Participants Participants in the "Depressed' arm first received Hydrocortisone 160 mg tablet every day for 3 days. After a washout period of 25 days, they then received a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.	Depressed: Placebo, Then Hydrocortisone n=11 Participants Participants in the "Depressed' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days. After a washout period of 25 days, they then received Hydrocortisone 160 mg tablet every day for 3 days.	Healthy Controls: Hydrocortisone, Then Placebo n=22 Participants Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days. After a washout period of 25 days, they then received a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.	Healthy Controls: Placebo, Then Hydrocortisone n=21 Participants Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days. After a washout period of 25 days, they then received Hydrocortisone 160 mg tablet every day for 3 days.	Total n=66 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants	0 Participants n=16 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=9 Participants	11 Participants n=6 Participants	22 Participants n=9 Participants	21 Participants n=205 Participants	66 Participants n=16 Participants
Age, Categorical >=65 years	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants	0 Participants n=16 Participants
Age, Continuous	32.25 Years STANDARD_DEVIATION 11.07 • n=9 Participants	41.73 Years STANDARD_DEVIATION 8.57 • n=6 Participants	29.45 Years STANDARD_DEVIATION 9.26 • n=9 Participants	31.00 Years STANDARD_DEVIATION 9.36 • n=205 Participants	32.50 Years STANDARD_DEVIATION 10.43 • n=16 Participants
Sex: Female, Male Female	9 Participants n=9 Participants	9 Participants n=6 Participants	14 Participants n=9 Participants	10 Participants n=205 Participants	42 Participants n=16 Participants
Sex: Female, Male Male	3 Participants n=9 Participants	2 Participants n=6 Participants	8 Participants n=9 Participants	11 Participants n=205 Participants	24 Participants n=16 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants	0 Participants n=16 Participants
Race (NIH/OMB) Asian	1 Participants n=9 Participants	1 Participants n=6 Participants	4 Participants n=9 Participants	4 Participants n=205 Participants	10 Participants n=16 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants	0 Participants n=16 Participants
Race (NIH/OMB) Black or African American	1 Participants n=9 Participants	5 Participants n=6 Participants	2 Participants n=9 Participants	2 Participants n=205 Participants	10 Participants n=16 Participants
Race (NIH/OMB) White	8 Participants n=9 Participants	5 Participants n=6 Participants	14 Participants n=9 Participants	15 Participants n=205 Participants	42 Participants n=16 Participants
Race (NIH/OMB) More than one race	2 Participants n=9 Participants	0 Participants n=6 Participants	2 Participants n=9 Participants	0 Participants n=205 Participants	4 Participants n=16 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants	0 Participants n=16 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=9 Participants	2 Participants n=6 Participants	8 Participants n=9 Participants	9 Participants n=205 Participants	22 Participants n=16 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=9 Participants	9 Participants n=6 Participants	14 Participants n=9 Participants	10 Participants n=205 Participants	42 Participants n=16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	2 Participants n=205 Participants	2 Participants n=16 Participants

PRIMARY outcome

Timeframe: 3 days

The z-scores of hippocampal subregions and hemispheres represent the standardized difference in activation between correct and incorrect conditions of the mnemonic discrimination task, where a Z-score of 0 represents the mean difference across all voxels, and each unit reflects one standard deviation from that mean. To compare brain activation between conditions, separate beta weights were estimated for correct and incorrect trials across all trials. These beta weights represent the voxel-wise blood oxygen level (BOLD)-dependent signal, reflecting changes in neural activity associated with each condition. Positive z-scores indicate greater activation for correct relative to incorrect trials, whereas negative z-scores indicate greater activation for incorrect relative to correct trials. Larger absolute z-scores indicate stronger condition-related effects; there are no established clinical thresholds for these experimental activation differences.

Outcome measures

Outcome measures
Measure	Healthy Controls: Placebo n=16 Participants Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Depressed: Hydrocortisone n=13 Participants Participants in the "Depressed' arm who received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Depressed: Placebo n=11 Participants Participants in the "Depressed' arm who received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Healthy Controls: Hydrocortisone n=15 Participants Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.
Hippocampal Subfield Activation (Left Hemisphere)	-0.07 Z-Score Standard Deviation 0.53	-0.35 Z-Score Standard Deviation 0.76	0.03 Z-Score Standard Deviation 0.25	-0.08 Z-Score Standard Deviation 0.57

PRIMARY outcome

Timeframe: 3 days

Outcome measures

Outcome measures
Measure	Healthy Controls: Placebo n=16 Participants Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Depressed: Hydrocortisone n=13 Participants Participants in the "Depressed' arm who received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Depressed: Placebo n=11 Participants Participants in the "Depressed' arm who received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Healthy Controls: Hydrocortisone n=15 Participants Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.
Hippocampal Subfield Activation (Right Hemisphere)	-0.24 Z-Score Standard Deviation 0.37	-0.05 Z-Score Standard Deviation 0.47	-0.04 Z-Score Standard Deviation 0.41	-0.09 Z-Score Standard Deviation 0.50

PRIMARY outcome

Timeframe: 3 days

High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.

Outcome measures

Outcome measures
Measure	Healthy Controls: Placebo n=33 Participants Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Depressed: Hydrocortisone n=18 Participants Participants in the "Depressed' arm who received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Depressed: Placebo n=17 Participants Participants in the "Depressed' arm who received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Healthy Controls: Hydrocortisone n=36 Participants Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.
Hippocampal Subfield Volume (Left Hemisphere)	50.55 Cubic Millimeter Standard Deviation 13.78	56.05 Cubic Millimeter Standard Deviation 15.67	54.65 Cubic Millimeter Standard Deviation 13.90	54.52 Cubic Millimeter Standard Deviation 12.43

PRIMARY outcome

Timeframe: 3 days

High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.

Outcome measures

Outcome measures
Measure	Healthy Controls: Placebo n=33 Participants Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Depressed: Hydrocortisone n=18 Participants Participants in the "Depressed' arm who received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Depressed: Placebo n=17 Participants Participants in the "Depressed' arm who received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Healthy Controls: Hydrocortisone n=36 Participants Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.
Hippocampal Subfield Volume (Right Hemisphere)	62.03 Cubic Millimeter Standard Deviation 17.08	65.95 Cubic Millimeter Standard Deviation 20.29	66.10 Cubic Millimeter Standard Deviation 20.68	65.65 Cubic Millimeter Standard Deviation 16.38

Adverse Events

Depressed: Hydrocortisone

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Depressed: Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Healthy Controls: Hydrocortisone

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Healthy Controls: Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Depressed: Hydrocortisone n=19 participants at risk Participants in the "Depressed' arm who received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Depressed: Placebo n=21 participants at risk Participants in the "Depressed' arm who received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Healthy Controls: Hydrocortisone n=42 participants at risk Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Healthy Controls: Placebo n=37 participants at risk Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.
Psychiatric disorders Suicidal Ideation	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	4.8% 1/21 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.

Other adverse events

Additional Information

Dr. E. Sherwood Brown

University of Texas Southwestern Medical Center

Phone: 214-645-6950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Depressed: Hydrocortisone n=19 participants at risk Participants in the "Depressed' arm who received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Depressed: Placebo n=21 participants at risk Participants in the "Depressed' arm who received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.	Healthy Controls: Hydrocortisone n=42 participants at risk Participants in the "Healthy Controls' arm first received Hydrocortisone 160 mg tablet every day for 3 days as the first or second intervention.	Healthy Controls: Placebo n=37 participants at risk Participants in the "Healthy Controls' arm first received Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days as the first or second intervention.
Nervous system disorders Daytime Somnolence	5.3% 1/19 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Nervous system disorders Nightmares	5.3% 1/19 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
General disorders Difficulty Sleeping	5.3% 1/19 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.7% 1/37 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
General disorders Flushing in Face	5.3% 1/19 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Gastrointestinal disorders Burning Sensation in Stomach	5.3% 1/19 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Gastrointestinal disorders Nausea	5.3% 1/19 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	4.8% 1/21 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Nervous system disorders MRI Abnormality	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	4.8% 1/21 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
General disorders Increased Energy	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	4.8% 1/21 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Skin and subcutaneous tissue disorders Hives	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	4.8% 1/21 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Gastrointestinal disorders Flatulence	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
General disorders Restlessness	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Gastrointestinal disorders Loose Stool	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Skin and subcutaneous tissue disorders Acne Exacerbation	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.7% 1/37 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Skin and subcutaneous tissue disorders Eczema Flare	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.4% 1/42 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/37 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
General disorders Racing Thoughts	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.7% 1/37 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Gastrointestinal disorders Abdominal Bloating	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.7% 1/37 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Infections and infestations Fever Blister	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.7% 1/37 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.
Nervous system disorders Headache	0.00% 0/19 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/21 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	0.00% 0/42 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.	2.7% 1/37 • Number of events 1 • The period of observation for the collection of adverse events extended from the time the subject gave informed consent until study completion, an average of 40 days.