Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01849250
• Collaborator: (none)
• Enrollment: 65
• Locations: 4
• Arms: 2
• Actual Duration (Months): 83.7
• Patients Per Site: 16.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well docosahexaenoic acid works in preventing recurrence in breast cancer survivors. Docosahexaenoic acid supplement may prevent recurrence in breast cancer survivors.

Condition or Disease	Intervention/Treatment	Phase
Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer	Drug: Docosahexaenoic Acid; Other: Placebo	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether treatment with docosahexaenoic acid (DHA) for 12 weeks at 1000 mg twice daily as compared to placebo reduces normal breast tissue levels of tumor necrosis factor-alpha (TNF-alpha) in overweight and obese patients with a history of stage I-III invasive breast cancer, ductal carcinoma in situ (DCIS), Paget's disease, lobular carcinoma in situ (LCIS), or proliferative benign breast disease.

SECONDARY OBJECTIVES:

1. To investigate the effect of DHA at 1000 mg twice daily on tissue biomarkers

• Change from the baseline in cyclooxygenase-2 (COX-2)/interleukin-1-beta (IL-1beta)/aromatase measured by quantitative real-time polymerase chain reaction (PCR).

• Change from the baseline in crown-like structures of the breast (CLS-B) measured by immunohistochemical techniques for cluster of differentiation (CD)68.

• Change from baseline in CLS-B index determined as follows: ([number of slides with evidence of at least one CLS-B]/[total number of slides examined]).

• Change from baseline in CLS-B/cm^{2 defined as the number of CLS-B/cm}2. II. Evaluate age as a predictor of CLS-B and inflammatory biomarkers (TNF-alpha/COX-2/IL-1beta) at baseline and over the time of treatment.

1. Evaluate red blood cell (RBC) fatty acid level as a surrogate of compliance.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive docosahexaenoic acid orally (PO) twice daily (BID) for 12 weeks.

ARM II: Patients receive placebo PO BID for 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Patients With a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: Jan 11, 2016
• Actual Study Completion Date: Apr 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (Docosahexaenoic Acid) Docosahexaenoic Acid orally twice a day (PO BID) for 12 weeks.	Drug: Docosahexaenoic Acid; Given PO; Other Names: Fatty Acid 22:6
Placebo Comparator: Arm II (placebo) Placebo orally twice a day (PO BID) for 12 weeks.	Other: Placebo; Given PO; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels [Baseline to 12 weeks]

   Differences in normal breast tissue levels of TNF-α 12 weeks post-treatment relative to pre-treatment for active treatment and placebo arm, compared using analysis of covariance where the post-treatment measurements were used as a dependent variable and the pretreatment measurements were included as a covariate in the analysis. For the primary study end-point TNF-α levels will be measured by quantitative real-time PCR (mRNA essays) on extracted RNA from breast core biopsies. Relative expression determined using the Computed Tomography (ΔΔCT) analysis protocol.

Secondary Outcome Measures

1. Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment [Baseline to 12 weeks]

   An indicator of whether a subject is detected with CLS-B or not.

2. Absolute Change in CLS-B/cm^2 Adjusted for the Pre-treatment Measurements [Baseline to 12 weeks]

   To assess the severity of CLS-B using the following formula: number of CLS-B/cm^2. The absolute change in the CLS-B/cm^2 calculated according to the formula; Change in CLS-B/cm^2 = (post-treatment CLS-B/cm^2) - (pre-treatment CLS-B/cm^2).

3. Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks [Baseline to 12 weeks]

   Biomarkers COX-2 are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.

4. Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers [Baseline to 12 weeks]

   Biomarkers IL-1Beta are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.

5. Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers [Baseline and 12 weeks]

   Biomarkers Aromatase are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.

6. Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance [Baseline and week 12]

   Whole blood samples collected for red blood cell fatty acid analyses at baseline and week 12 (+ 2 weeks). RBC fatty acid composition analyzed by gas chromatography (GC) with flame ionization detection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must have a history of histologically-confirmed stage I-III invasive breast cancer or ductal carcinoma in situ (DCIS), Paget's disease, lobular carcinoma in situ (LCIS), or proliferative benign breast disease

• No evidence of disease (in situ or invasive cancer that would normally be treated by resection) at trial entry as determined by the investigator

• = 6 months from all previous breast cancer treatment (including surgery for invasive cancer, chest wall radiotherapy, chemotherapy, trastuzumab and endocrine therapy)

• Participants must have a body mass index (BMI) >= 25, defined as (weight in kilograms/[height in meters]^2)

• Participants must have adequate accessible breast tissue as determined by the treating physician, consisting of one breast unaffected by invasive cancer, which has not been radiated; a history of prior pre-invasive breast cancer or benign biopsy of this breast will be permitted

• Daily DHA consumption =< 200 mg/day in the month prior to screening estimated by an abbreviated DHA food frequency questionnaire

• Mammogram within no more than 6 months prior to the date of informed consent (normal/benign Breast Imaging-Reporting and Data System [BI-RADS] 1 or 2) and no further routine breast imaging planned during the course of the study (12 weeks DHA/placebo)

• Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2 (Karnofsky

= 60%)

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 75,000/uL

• White blood cells >= 3,000/uL

• Hemoglobin >= 10 g/dL

• Total bilirubin within 1.5 times the institution's upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within 1.5 times the institution's ULN

• Serum creatinine within 1.5 times the institution's ULN

• Pregnant women will be excluded; for women of childbearing potential; negative pregnancy testing within 72 hours prior to or on study visit #1 (day 0) and willingness to use adequate contraception during the study intervention OR post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy

• Willingness to comply with all study interventions and follow-up procedures including the ability to swallow the study drug

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Any type of active invasive cancer (excluding breast and non-melanoma skin cancer) within the preceding 18 months

• A history of histologically-confirmed bilateral invasive breast cancer

• Bilateral mastectomy

• Prior history or evidence of metastatic breast cancer

• Prior radiation therapy to the contralateral (unaffected) breast

• Prior history of contralateral (unaffected) breast augmentation with breast implant placement

• History of daily use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) in the week preceding study entry

• History of DHA supplementation > 200 mg/day in the month preceding study entry

• History of autoimmune disorder or any illness that requires therapy with chronic steroids or immunomodulators

• History of therapeutic doses of anticoagulants including warfarin and low molecular weight heparin (e.g. for prior deep venous thrombosis and pulmonary embolism) in the preceding year

• Participants may not be receiving any other investigational agents during the study

• Women who have received cancer surgery, chemotherapy, biological therapy (e.g., trastuzumab), or radiotherapy for the treatment of any cancer within 6 months of study participation

• Women who are receiving endocrine therapy for breast cancer treatment or chemoprevention including tamoxifen, letrozole, anastrozole, fulvestrant, or exemestane at the time of screening

• Individuals with severe underlying chronic illness, such as uncontrolled diabetes; ongoing or active infection, psychiatric illness or social situations which in the opinion of the investigator would interfere with study participation

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to DHA or corn/soy oil in placebo agent

• Pregnant, breastfeeding, or women of childbearing potential unwilling to use a reliable contraceptive method

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Columbia University/Herbert Irving Cancer Center	New York	New York	United States	10032
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
4	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ayca Gucalp, Memorial Sloan Kettering Cancer Center
• Study Chair: Powel H. Brown, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01849250
• Other Study ID Numbers: NCI-2013-00859; NCI-2013-00859; 12-474; 12-267; N01-CN-2012-00034; DFCI:12- 474; AAAK6752; MSKCC-12-267; H-33017; CUMC: AAAK6752; 2011-0766; MDA10-16-01; N01CN00034; N01CN35159; P30CA016672
• First Posted: May 8, 2013
• Last Update Posted: Dec 28, 2021
• Last Verified: Dec 1, 2021

• Additional relevant MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Paget's Disease, Mammary; Breast Diseases

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 1 ,2013 to December 31, 2015. All recruitment done in medical settings.
Pre-assignment Detail	Of 65 participants enrolled, one was not eligible thus excluded from the study.

Arm/Group Title	Placebo	Docosahexaenoic Acid (DHA)
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid 1000 mg orally twice a day for 12 weeks.
Period Title: Overall Study
STARTED	32	32
COMPLETED	25	29
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Placebo	Docosahexaenoic Acid	Total
Arm/Group Description	Placebo orally twice a day for 12 weeks.	DHA 1000 mg orally twice a day for 12 weeks.	Total of all reporting groups
Overall Participants	32	32	64
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57	59.5	59
Sex: Female, Male (Count of Participants)
Female	32 100%	32 100%	64 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 15.6%	1 3.1%	6 9.4%
Not Hispanic or Latino	22 68.8%	25 78.1%	47 73.4%
Unknown or Not Reported	5 15.6%	6 18.8%	11 17.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.1%	0 0%	1 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 6.3%	4 12.5%	6 9.4%
White	27 84.4%	28 87.5%	55 85.9%
More than one race	1 3.1%	0 0%	1 1.6%
Unknown or Not Reported	1 3.1%	0 0%	1 1.6%
Region of Enrollment (participants) [Number]
United States	32 100%	32 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels
Description	Differences in normal breast tissue levels of TNF-α 12 weeks post-treatment relative to pre-treatment for active treatment and placebo arm, compared using analysis of covariance where the post-treatment measurements were used as a dependent variable and the pretreatment measurements were included as a covariate in the analysis. For the primary study end-point TNF-α levels will be measured by quantitative real-time PCR (mRNA essays) on extracted RNA from breast core biopsies. Relative expression determined using the Computed Tomography (ΔΔCT) analysis protocol.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

6 participants in the Placebo group and 1 participant in the DHA group were not evaluable due to tissue was not available quantitative RT-PCR.

Arm/Group Title	Placebo	Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Measure Participants	26	31
Baseline	0.26 (0.93)	0.08 (0.78)
Post-Treatment	0.06 (0.92)	0.16 (0.95)
Post-treatment vs. Baseline Change	-0.22 (1.19)	0.08 (0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.50
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment
Description	An indicator of whether a subject is detected with CLS-B or not.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

4 participants on the placebo arm and 1 participant on the DHA arm did not have a post treatment biopsy.

Arm/Group Title	Placebo	Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Measure Participants	28	31
Baseline	2 6.3%	4 12.5%
Post-treatment	3 9.4%	3 9.4%
Positive both Baseline and Post-treatment	2 6.3%	0 0%

3. Secondary Outcome

Title	Absolute Change in CLS-B/cm^2 Adjusted for the Pre-treatment Measurements
Description	To assess the severity of CLS-B using the following formula: number of CLS-B/cm^2. The absolute change in the CLS-B/cm^2 calculated according to the formula; Change in CLS-B/cm^2 = (post-treatment CLS-B/cm^2) - (pre-treatment CLS-B/cm^2).
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Placebo	Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Measure Participants	0	0

4. Secondary Outcome

Title	Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks
Description	Biomarkers COX-2 are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with adequate RNA available were analyzed.

Arm/Group Title	Placebo	Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Measure Participants	14	23
Baseline COX-2	0.49 (1.35)	0.31 (0.97)
Post-Treatment COX-2	-0.11 (1.30)	0.22 (1.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Docosahexaenoic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.19
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers
Description	Biomarkers IL-1Beta are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with adequate RNA available were analyzed.

Arm/Group Title	Placebo	Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Measure Participants	26	31
Baseline IL-Beta	0.62 (2.00)	0.28 (1.50)
Post-treatment IL-Beta	0.23 (2.06)	0.19 (2.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Docosahexaenoic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.52
	Comments
	Method	ANOVA
	Comments

6. Secondary Outcome

Title	Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers
Description	Biomarkers Aromatase are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with adequate RNA available were analyzed.

Arm/Group Title	Placebo	Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Measure Participants	22	30
Baseline Aromatase	-0.38 (1.93)	0.13 (2.38)
Post-treatment Aromatase	-0.59 (2.13)	0.06 (1.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Docosahexaenoic Acid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.12
	Comments
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance
Description	Whole blood samples collected for red blood cell fatty acid analyses at baseline and week 12 (+ 2 weeks). RBC fatty acid composition analyzed by gas chromatography (GC) with flame ionization detection.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Available blood samples.

Arm/Group Title	Placebo	Docosahexaenoic Acid (DHA)
Arm/Group Description	Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid 1000 mg orally twice a day for 12 weeks.
Measure Participants	28	30
Baseline Omega3 index	5.03 (1.65)	5.01 (1.13)
Baseline DHA level	4.53 (1.5)	4.47 (0.98)
Post-Treatment Omega3 index	4.92 (1.68)	11.95 (1.35)
Post-Treatment DHA level	4.41 (1.48)	11.2 (1.33)
Post Treatment v. Baseline Change Omega3 index	-0.10 (.068)	6.99 (1.43)
Post Treatment v. Baseline Change DHA level	-0.12 (0.59)	6.78 (1.42)

Adverse Events

Time Frame	Adverse events collected over 12 weeks of treatment.
Arm/Group Title	Placebo		Docosahexaenoic Acid
Arm/Group Description	Placebo orally twice a day for 12 weeks.		Docosahexaenoic Acid 1000 mg orally twice a day for 12 weeks.
All Cause Mortality
	Placebo		Docosahexaenoic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Docosahexaenoic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Docosahexaenoic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/32 (53.1%)		15/32 (46.9%)
Blood and lymphatic system disorders
Anemia	0/32 (0%)	0	2/32 (6.3%)	2
Cardiac disorders
Heart failure, Congestive	1/32 (3.1%)	1	0/32 (0%)	0
Ear and labyrinth disorders
Vertigo	0/32 (0%)	0	1/32 (3.1%)	1
Gastrointestinal disorders
Bloating	1/32 (3.1%)	1	0/32 (0%)	0
Colitis	1/32 (3.1%)	1	0/32 (0%)	0
Diarrhea	2/32 (6.3%)	3	1/32 (3.1%)	2
Dyspepsia - Heart Burn	0/32 (0%)	0	1/32 (3.1%)	1
Flatulence	0/32 (0%)	0	1/32 (3.1%)	1
Gastroesophageal reflux disease	1/32 (3.1%)	1	1/32 (3.1%)	1
Gastrointestinal disorders - Other: Burping	5/32 (15.6%)	5	2/32 (6.3%)	2
Gastrointestinal disorders - Other: Diverticulitis	1/32 (3.1%)	1	0/32 (0%)	0
Gastrointestinal disorders - Other: Loose stool	1/32 (3.1%)	1	0/32 (0%)	0
Nausea	1/32 (3.1%)	1	0/32 (0%)	0
Oral pain	1/32 (3.1%)	1	0/32 (0%)	0
Vomiting	2/32 (6.3%)	2	0/32 (0%)	0
General disorders
Fatigue	1/32 (3.1%)	1	0/32 (0%)	0
Flu like symptoms	0/32 (0%)	0	1/32 (3.1%)	1
Localized edema	0/32 (0%)	0	1/32 (3.1%)	1
Pain	0/32 (0%)	0	1/32 (3.1%)	1
Infections and infestations
Otitis media	1/32 (3.1%)	1	0/32 (0%)	0
Sinusitis	1/32 (3.1%)	1	1/32 (3.1%)	1
Injury, poisoning and procedural complications
Bruising	1/32 (3.1%)	1	1/32 (3.1%)	1
Fall	0/32 (0%)	0	1/32 (3.1%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/32 (3.1%)	1	0/32 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/32 (3.1%)	1	0/32 (0%)	0
Back pain	2/32 (6.3%)	2	1/32 (3.1%)	1
Myalgia	2/32 (6.3%)	2	1/32 (3.1%)	1
Neck pain	1/32 (3.1%)	1	0/32 (0%)	0
Nervous system disorders
Headache	1/32 (3.1%)	1	2/32 (6.3%)	2
Reproductive system and breast disorders
Breast pain	1/32 (3.1%)	1	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/32 (3.1%)	1	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders - Other, Chest Congestion	0/32 (0%)	0	1/32 (3.1%)	1
Sore throat	0/32 (0%)	0	1/32 (3.1%)	1
Upper respiratory infection	1/32 (3.1%)	1	0/32 (0%)	0
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - other, Poison Ivy Rash	1/32 (3.1%)	1	0/32 (0%)	0
Skin infection	0/32 (0%)	0	1/32 (3.1%)	1
Urticaria	0/32 (0%)	0	1/32 (3.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.