Study to Treat Major Depressive Disorder With a New Medication

• Sponsor: James Murrough (Other)
• Overall Status: Completed
• CT.gov ID: NCT03043560
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Baylor College of Medicine (Other)
• Enrollment: 45
• Locations: 2
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site: 22.5
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This project is designed to examine the neuronal KCNQ2/3 potassium (K+) channel subtype as a novel treatment target for mood disorders through the administration of the KCNQ-selective channel opener ezogabine (Potiga, GlaxoSmithKline; FDA-approved for the treatment of seizure disorders).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder; Anhedonia	Drug: Ezogabine; Drug: Placebos	Phase 2

Detailed Description

Depressive disorders are among the most disabling medical conditions worldwide and currently available treatments fall short of addressing this large public health burden. Dysfunction within the brain reward system is emerging as a core feature of depressive disorders, in particular related to deficits in motivation, interest, and response to pleasure (e.g., anhedonia: markedly diminished response to pleasure). Evidences from a series of preclinical studies from our group highlighted the KCNQ subtype of neuronal potassium (K+) channel as a novel target for the treatment of depressive disorders and our human pilot study showed a reduction in anhedonia and related symptoms, and an increased brain response to reward (as measured by functional magnetic resonance imaging [fMRI]) following treatment with ezogabine. Building on this data, the current project will assess reward circuit activity following treatment with ezogabine in depressed patients with a current depressive disorder (Major depressive disorder [MDD], persistent depressive disorder, other specified depressive disorder) and anhedonia (defined by a score ≥ 20 on the Snaith-Hamilton Pleasure Scale [SHAPS]), using fMRI to investigate the cortico-striatal circuit to reward.

This study represents the first part of the R61/R33 National Institutes of Health (NIH) founded project. A clear increase in reward circuit activation in at least one ezogabine treatment group compared to placebo, given acceptable tolerability, will constitute a "go" and the project will move to the next phase (R33), where we aim to examine the relationship between treatment, reward circuit activity, and behavioral and clinical outcomes in a larger, confirmatory efficacy trial of ezogabine for depression with anhedonia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double blind
• Primary Purpose: Other
• Official Title: Developing Neuronal KCNQ Channel Modulators for Mood Disorders
• Actual Study Start Date: Sep 25, 2017
• Actual Primary Completion Date: Aug 30, 2019
• Actual Study Completion Date: Aug 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ezogabine Participants will receive treatment with ezogabine up to 900mg/day.	Drug: Ezogabine; daily for 5 weeks; Other Names: Potiga
Placebo Comparator: Placebo Participants will receive treatment with a matching placebo pill.	Drug: Placebos; placebo pill daily for 5 weeks

Outcome Measures

Primary Outcome Measures

1. Change in Ventral Striatum (VS) Activation [baseline and 5 weeks]

   change in activation during reward anticipation within the bilateral VS from baseline (Study Visit 0) to the primary outcome visit (Study Visit 5) as measured by functional MRI during the incentive flanker task (IFT). The IFT, like the Monetary Incentive Delay task, permits discrete modeling of brain activity during anticipation of an incentive. Functional scans were preprocessed and denoised for motion and physiological noise using multi-echo independent component analysis (ME-ICA). Task-based modeling was conducted using AFNI and FSL software. The primary outcome for reward anticipation was the contrast of reward cue compared to neutral cue (reward>neutral cue). The primary imaging outcome was analyzed using a linear mixed model with a single random intercept term treating time as discrete or continuous as appropriate.

Secondary Outcome Measures

1. Change in Snaith-Hamilton Pleasure Scale (SHAPS) [baseline and 5 weeks]

   The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are coded as "1", while a "strongly disagree" response was assigned a score of "4." Total scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.

2. Clinical Global Impression - Improvement (CGI-I) [baseline and 5 weeks]

   A widely administered clinician rated global measure of the degree of improvement from the initial assessment in subject overall illness severity. 7 point scale rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.

3. Clinical Global Impression - Severity (CGI-S) [baseline and 5 weeks]

   Clinician rated global measure of subject overall illness severity. a 7-point scale rated as 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

4. Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) [baseline and 5 weeks]

   A measure specifically designed to assess hedonic capacity for social and interpersonal pleasure.The ACIPS is a 17-item self-report measure scored on a likert scale, ranging from 1 (very false for me) to 6 (very true for me). Full scale from 17-102, higher score indicates higher hedonic capacity

5. Montgomery-Asberg Depression Rating Scale (MADRS) [baseline and 5 weeks]

   A 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).

6. World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) [baseline and 5 weeks]

   A 12-item generic assessment instrument that measures the level of functioning. Each item is scored from 0 to 4 and the items are summed to provide a total score. The score therefore ranges from 0 to 48, with higher scores indicating greater disability.

7. Temporal Experience of Pleasure Scale (TEPS) [baseline and 5 weeks]

   The TEPS is composed of 18-items rated on a likert-type scale ranging from 1 (Very True for me) to 6 (Very False for me), and yields two subscales. Ten items make up the TEPS-Anticipatory Pleasure (TEPS-ANT) scale with a range from 10 (not motivated) to 60 (highly motivated). The other eight TEPS items make up the TEPS-Consummatory Pleasure (TEPS-CON) scale; range from 8 (not responsive) to 48 (highly responsive). Total scores range is 18-108. Lower scores indicate greater levels of anhedonia.

8. Specific Loss of Interest and Pleasure Scale (SLIPS) [baseline 5 weeks]

   The SLIPS is a recently developed and validated measure of anhedonia that is tailored to detect recent changes in anhedonia. A 23-item measure, each item range from 0-3. Full scale from 0 to 69, higher score indicates more recent changes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study;

• Men and women, age 18-65;

• Participants must meet DSM-V criteria for current depressive disorder (major depressive disorder [MDD], persistent depressive disorder, other specified depressive disorder) as determined by a study psychiatrist and confirmed using the Structured Clinical Interview for DSM-V (SCID);

• Clinically significant anhedonia as determined by a SHAPS score ≥ 20 at screening;

• Current illness severity is at least moderate, defined as a score of ≥4 on the Clinical Global Impression-Severity (CGI-S) Scale;

• If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinence.

Exclusion Criteria:

• A primary psychiatric diagnosis other than a depressive disorder as defined by DSM-V [co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD) are allowed] or major cognitive disorder;

• Meets criteria for a substance or alcohol use disorder in the past 6 months;

• Female participants who are pregnant, breastfeeding, or may become pregnant, or unwilling to practice birth control during participation in the study;

• Positive urine toxicology screen for drugs of abuse at the time of screening;

• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease;

• Clinically significant abnormalities of laboratory tests, physical examination, or ECG;

• Prolonged QT Interval at screening, operationalized as a QTc of > 480 ms;

• A history of retinal abnormalities (i.e., pigment changes, retinal dystrophy) or findings of retinal pathology on ophthalmological exam at baseline;

• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data;

• Use of any dis-allowed medication according to the study protocol;

• Serious and imminent risk of self harm or violence as determined by the PI;

• Extreme illness severity as defined by a GCI-S score >6;

• Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more;

• History of non-response to electroconvulsive therapy in the current depressive episode

• Exceptions:

1. Subjects with a positive urine drug screen for cannabinoids, barbiturates, opiates, amphetamines, or benzodiazepines may be allowed in the study provided that the drug was used for a documented, legitimate medical purpose and/or the use of such products may be discontinued (documented by a negative repeat test) prior to randomization;

2. Medically appropriate episodic use (up to 3 days) of narcotic analgesics for acute medical indications is allowed (Discussion with PI required)

• Potential participants will not be discontinued from medication for the purposes of this study. If a patient is taking a protocol dis-allowed medication at the time of screening, the patient may discontinue the medication under the supervision of the treating physician in the case that the patient is not benefiting from the medication or otherwise wishes to discontinue the medication. In no case will a dis-allowed medication be discontinued for the purpose of study participation if the patient is receiving clinical benefit from the medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
2	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• James Murrough
• National Institute of Mental Health (NIMH)
• Baylor College of Medicine

Investigators

• Principal Investigator: James Murrough, MD, PhD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 1, 2018
• Study Protocol - Jun 12, 2019

More Information

Publications

None provided.

• Responsible Party: James Murrough, Associate Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03043560
• Other Study ID Numbers: GCO 16-0374; 1R61MH111932-01
• First Posted: Feb 6, 2017
• Last Update Posted: Oct 23, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by James Murrough, Associate Professor, Icahn School of Medicine at Mount Sinai: depression; anhedonia; reward
• Additional relevant MeSH terms: Anhedonia; Depressive Disorder; Depression; Ezogabine

Study Results

Participant Flow

Recruitment Details	Participants recruited from Sept 2017 through August 2019

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Period Title: Overall Study
STARTED	21	24
COMPLETED	20	21
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Ezogabine	Placebo	Total
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks	Total of all reporting groups
Overall Participants	21	24	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.4 (13.6)	38.9 (14.3)	41.5 (14.1)
Sex: Female, Male (Count of Participants)
Female	10 47.6%	12 50%	22 48.9%
Male	11 52.4%	12 50%	23 51.1%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	12 57.1%	12 50%	24 53.3%
Black/African American	5 23.8%	7 29.2%	12 26.7%
Hispanic/Latino	6 28.6%	9 37.5%	15 33.3%
Employment at least Part-Time (Count of Participants)
Count of Participants [Participants]	9 42.9%	14 58.3%	23 51.1%
Educational Attainment - ast least some college (Count of Participants)
Count of Participants [Participants]	15 71.4%	21 87.5%	36 80%
Relationship Status - Single, Never Married (Count of Participants)
Count of Participants [Participants]	8 38.1%	13 54.2%	21 46.7%
Primary Diagnosis (Count of Participants)
Major Depressive Disorder	21 100%	23 95.8%	44 97.8%
Persistent Depressive Disorder	0 0%	1 4.2%	1 2.2%
Current Major Depressive Episode (Count of Participants)
Count of Participants [Participants]	21 100%	22 91.7%	43 95.6%
Age at Onset of Depression (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.3 (15.6)	21.7 (11.5)	24.3 (14.0)
Current Depressive Episode Duration (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	72	24	30
Generalized Anxiety Disorder (Count of Participants)
Count of Participants [Participants]	11 52.4%	10 41.7%	21 46.7%
Posttraumatic Stress Disorder (PTSD) (Count of Participants)
Count of Participants [Participants]	4 19%	8 33.3%	12 26.7%

Outcome Measures

1. Primary Outcome

Title	Change in Ventral Striatum (VS) Activation
Description	change in activation during reward anticipation within the bilateral VS from baseline (Study Visit 0) to the primary outcome visit (Study Visit 5) as measured by functional MRI during the incentive flanker task (IFT). The IFT, like the Monetary Incentive Delay task, permits discrete modeling of brain activity during anticipation of an incentive. Functional scans were preprocessed and denoised for motion and physiological noise using multi-echo independent component analysis (ME-ICA). Task-based modeling was conducted using AFNI and FSL software. The primary outcome for reward anticipation was the contrast of reward cue compared to neutral cue (reward>neutral cue). The primary imaging outcome was analyzed using a linear mixed model with a single random intercept term treating time as discrete or continuous as appropriate.
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	-0.26 (0.69)	0.95 (0.79)
5 weeks	0.176 (0.81)	0.015 (0.68)

2. Secondary Outcome

Title	Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Description	The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are coded as "1", while a "strongly disagree" response was assigned a score of "4." Total scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
Baseline	38.7 (8.1)	33.7 (6)
5 weeks	27.5 (8.5)	30 (10.9)

3. Secondary Outcome

Title	Clinical Global Impression - Improvement (CGI-I)
Description	A widely administered clinician rated global measure of the degree of improvement from the initial assessment in subject overall illness severity. 7 point scale rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	4 (0.2)	4 (0.4)
5 weeks	2.1 (1)	2.8 (1.3)

4. Secondary Outcome

Title	Clinical Global Impression - Severity (CGI-S)
Description	Clinician rated global measure of subject overall illness severity. a 7-point scale rated as 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	4.4 (0.5)	4.6 (0.6)
5 weeks	2.6 (1.2)	3.3 (1.2)

5. Secondary Outcome

Title	Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
Description	A measure specifically designed to assess hedonic capacity for social and interpersonal pleasure.The ACIPS is a 17-item self-report measure scored on a likert scale, ranging from 1 (very false for me) to 6 (very true for me). Full scale from 17-102, higher score indicates higher hedonic capacity
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	46.1 (15.1)	53.7 (15)
5 weeks	65.1 (22.8)	59 (23.5)

6. Secondary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Description	A 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	28.3 (6.1)	26.8 (5.1)
5 weeks	12.7 (8.7)	18.5 (10.1)

7. Secondary Outcome

Title	World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
Description	A 12-item generic assessment instrument that measures the level of functioning. Each item is scored from 0 to 4 and the items are summed to provide a total score. The score therefore ranges from 0 to 48, with higher scores indicating greater disability.
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	15.5 (7.5)	16.5 (9.4)
5 weeks	10.2 (9.5)	11.6 (9.8)

8. Secondary Outcome

Title	Temporal Experience of Pleasure Scale (TEPS)
Description	The TEPS is composed of 18-items rated on a likert-type scale ranging from 1 (Very True for me) to 6 (Very False for me), and yields two subscales. Ten items make up the TEPS-Anticipatory Pleasure (TEPS-ANT) scale with a range from 10 (not motivated) to 60 (highly motivated). The other eight TEPS items make up the TEPS-Consummatory Pleasure (TEPS-CON) scale; range from 8 (not responsive) to 48 (highly responsive). Total scores range is 18-108. Lower scores indicate greater levels of anhedonia.
Time Frame	baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
TEPS-ANT baseline	26.3 (8.3)	28.6 (8.7)
TEPS-ANT 5 weeks	37.3 (10.5)	32.4 (11.5)
TEPS-CON baseline	24.8 (8.1)	25.6 (7.6)
TEPS-CON 5 weeks	32.2 (6)	29.9 (10.5)

9. Secondary Outcome

Title	Specific Loss of Interest and Pleasure Scale (SLIPS)
Description	The SLIPS is a recently developed and validated measure of anhedonia that is tailored to detect recent changes in anhedonia. A 23-item measure, each item range from 0-3. Full scale from 0 to 69, higher score indicates more recent changes.
Time Frame	baseline 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ezogabine	Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks	Matching placebo pill daily for 5 weeks
Measure Participants	21	24
baseline	32.3 (9.8)	28.8 (10.4)
5 weeks	16.3 (16.7)	21.5 (16.8)

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Ezogabine		Placebo
Arm/Group Description	Ezogabine up to 900mg/day daily for 5 weeks		Matching placebo pill daily for 5 weeks
All Cause Mortality
	Ezogabine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/24 (0%)
Serious Adverse Events
	Ezogabine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Ezogabine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		19/24 (79.2%)
Cardiac disorders
Palpitations	1/21 (4.8%)		1/24 (4.2%)
Eye disorders
Vision blurred	3/21 (14.3%)		1/24 (4.2%)
Gastrointestinal disorders
Abdominal Pain	2/21 (9.5%)		3/24 (12.5%)
Constipation	1/21 (4.8%)		2/24 (8.3%)
Diarrhea	5/21 (23.8%)		1/24 (4.2%)
Dry mouth	1/21 (4.8%)		0/24 (0%)
Nausea	3/21 (14.3%)		5/24 (20.8%)
Vomiting	2/21 (9.5%)		1/24 (4.2%)
General disorders
Malaise	1/21 (4.8%)		0/24 (0%)
Other	9/21 (42.9%)		8/24 (33.3%)
Infections and infestations
Upper respiratory tract infection	0/21 (0%)		1/24 (4.2%)
Metabolism and nutrition disorders
Increased appetite	1/21 (4.8%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	0/21 (0%)		1/24 (4.2%)
Nervous system disorders
Disturbance in attention	3/21 (14.3%)		0/24 (0%)
Dizziness	21/21 (100%)		5/24 (20.8%)
Headache	5/21 (23.8%)		7/24 (29.2%)
Memory impairment	1/21 (4.8%)		2/24 (8.3%)
Sedation	0/21 (0%)		1/24 (4.2%)
Somnolence	2/21 (9.5%)		3/24 (12.5%)
Psychiatric disorders
Anxiety	1/21 (4.8%)		1/24 (4.2%)
Confusional state	4/21 (19%)		0/24 (0%)
Panic attack	2/21 (9.5%)		0/24 (0%)
Restlessness	0/21 (0%)		1/24 (4.2%)
Renal and urinary disorders
Polyuria	0/21 (0%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	1/21 (4.8%)		1/24 (4.2%)
Nasal Congestion	1/21 (4.8%)		0/24 (0%)
Oropharyngeal pain	1/21 (4.8%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Rash	2/21 (9.5%)		0/24 (0%)

Limitations/Caveats

The relatively small sample size and termination of enrollment prior to the planned target limit conclusions regarding efficacy and generalizability.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.