Study of TNF-Antagonism in the Metabolic Syndrome (II)

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00413400
• Collaborator: Amgen (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This study will investigate whether etanercept will result in improved inflammatory indices, glucose tolerance and endothelial function in patients with the metabolic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome	Drug: Etanercept; Drug: Placebo	N/A

Detailed Description

Metabolic syndrome is an increasingly prevalent disorder associated with elevated risks of type II DM (diabetes mellitus) and cardiovascular morbidity and mortality. A subclinical inflammatory state is thought to contribute to the pathophysiology of metabolic syndrome, insulin resistance, and coronary artery disease (CAD). Tumor Necrosis Factor (TNF) -alpha is an inflammatory cytokine that is increased in a spectrum of inflammatory diseases as well as in insulin resistance. TNF-alpha antagonists are clinically effective in the inflammation of arthritides, and have recently been shown by our group to decrease inflammatory cardiovascular risk markers in metabolic syndrome. Data suggests that adiponectin, a recently discovered adipocytokine that may protect against the development of insulin resistance and atherosclerosis, may be downregulated by TNF-alpha. In addition, population based studies have shown that those with the highest levels of TNF-alpha have an increased relative risk of cardiovascular morbidity while rheumatoid arthritis patients treated with TNF-alpha blockade appear protected from cardiovascular disease. We will perform a 6-month study in which we will administer etanercept, a TNF-alpha receptor fusion protein, to subjects with metabolic syndrome to investigate its effect on surrogate markers of cardiovascular disease, including inflammatory markers, adiponectin and glucose tolerance and endothelial function. The results of the proposed study will have broad implications regarding the physiological role of TNF-alpha on the inflammatory cascade, cardiovascular indices and endothelial function.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Etanercept in Patients With the Metabolic Syndrome (II)
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; 50 mg one syringe sc 2x per week for three months followed by 50 mg one syringe sc 1X per week for three months
Active Comparator: Etanercept	Drug: Etanercept; 50 mg one syringe sc 2X per week for three months followed by 50 mg one syringe sc 1X per week for three months; Other Names: Enbrel

Outcome Measures

Primary Outcome Measures

1. C-reactive Protein (CRP) [6 months]

   As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported

2. Interleukin-6 (IL-6) [6 months]

   6 month value of IL-6 (pg/mL)

3. Adiponectin [6 months]

   The ratio of circulating high molecular weight (HMW) adiponectin to total adiponectin ratio (HMW:total Adiponectin) at 6 months is reported.

Secondary Outcome Measures

1. Glucose Tolerance [6 months]

   Fasting glucose (mg/dL) at 6mo

2. Endothelial Function [6 months]

   Reactive Hyperemia Index (RHI) using peripheral artery tonometry (using Endo-PAT 2000). Peripheral artery tonometry measures blood flow in the tip of the index finger at baseline and in response to vaso-occlusion (inflated blood pressure cuff). The reactive hyperemia index is an index of vasodilation after occlusion compared to baseline. A higher value indicates better vasoreactivity. As this is a relatively new test, there are no thoroughly validated clinically utilized norms.

3. White Blood Cell (WBC) Count [Baseline to 6 months]

   Change in WBC during study (WBC at six months minus WBC at baseline)

4. Cardiac Echo Ejection Fraction (EF) [Baseline to 6 months]

   change in EF (6mo - baseline). Please note that the value given is the absolute change in EF (which has units of percent), not the percent change in the variable.

5. Body Composition [6 months]

   6 month visceral adipose tissue (cm^2) - cross-sectional area of the visceral adipose tissue at the level of the 4th lumbar vertebrae was measured using single-slice abdominal computed tomography (CT) scan

6. Tumor Necrosis Factor (TNF) Receptor [6 months]

   Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months

7. Other Adipocytokines [6 months]

   circulating resistin at 6 months

8. Lipid Levels [6 months]

   total cholesterol (mg/dL) at 6 months

9. Adipocyte Messenger Ribonucleic Acid (mRNA) Levels of Adipocytokines Including Tumor Necrosis Factor (TNF) -Alpha [6 months]

   fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Hyperinsulinemia in the upper quartile of the non-diabetic population defined as >= 10 mU/mL (based on Framingham Data, oral communication, James Meigs, MD) or fasting glucose 110-126 mg/dL

2. Plus two of the following:

• Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women and BMI > 30 kg/m2

• Dyslipidemia including serum triglycerides >= 150 mg/dl or serum high density lipoprotein (HDL) < 0.9 mmol/L for men (35 mg/dL) and < 1.0 mmol/L (39mg/dL) for women

• Hypertension defined as blood pressure >= 140/90 or on medication

Exclusion Criteria:

1. Age < 18 or > 60 years

2. Body mass index (BMI) < 30 kg/m2

3. Positive tuberculosis (purified protein derivative [PPD]) skin test (5mm induration or more) on screening

4. Mycobacterial disease treated less than 6 months.

5. Current or recurrent infection or any underlying condition that may predispose to infection or anyone who has been admitted to the hospital due to bacteremia, pneumonia or any other serious infection.

6. Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months.

7. Prior or concurrent cyclophosphamide therapy

8. Use of a live vaccine 90 days prior to, or during this study.

9. History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.

10. Hemoglobin < 11 g/dl

11. History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers who will be eligible)

12. History of organ transplantation

13. HIV-positive status determined by HIV test at screening or known history of any other immuno-suppressing disease.

14. Hepatitis B or hepatitis C infection detected at screening, lupus (SLE), history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy

15. Patients with known autoimmune or inflammatory conditions (excluding patients with stable, treated hypothyroidism)

16. Severe comorbidities (diabetes mellitus requiring insulin, congestive heart failure (CHF) (EF<50% at baseline will be exclusionary) of any severity, myocardial infarction (MI), cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 3 months of screening visit, unstable angina pectoris, oxygen-dependent severe pulmonary disease

17. Uncontrolled systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg

18. Fasting blood glucose > 126 mg/dL

19. Creatinine > 1.5

20. Current use of insulin, any oral anti-hyperglycemic agents (including insulin sensitizing agents). Initiation of insulin, oral hypoglycemics, or insulin sensitizing agents during the study will result in discontinuation from the study.

21. Initiation of statins, niacin, antihypertensive or fibrate therapy within 6 weeks of the study. Chronic use of fibrates, niacin, or antihypertensives for > 6 weeks prior to study initiation at a stable dose is not exclusionary, but chronic use of statins for > 6 months is exclusionary. Initiation of statins, fibrates, niacin or antihypertensive treatments during the study is not exclusionary but will be considered in the analysis (see Protection against risks).

22. Positive pregnancy test or lactating females

23. Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (intrauterine device [IUD], condoms, diaphragms) or abstinence

24. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.

25. Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept

26. Concurrent sulfasalazine therapy

27. History of recent alcohol or substance abuse (< 1 year)

28. Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient.

29. History of non-compliance with other therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MGH	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Amgen

Investigators

• Principal Investigator: Steven K Grinspoon, MGH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00413400
• Other Study ID Numbers: 2006-P-001060
• First Posted: Dec 19, 2006
• Last Update Posted: Dec 2, 2010
• Last Verified: Nov 1, 2010

• Keywords provided by , ,: Inflammation; Visceral adiposity; TNF; Adiponectin; glucose tolerance; endothelial function; metabolic syndrome
• Additional relevant MeSH terms: Metabolic Syndrome; Syndrome; Etanercept

Study Results

Participant Flow

Recruitment Details	Recruitment period 12/2006 to 3/2009

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Period Title: Overall Study
STARTED	24	16
3 Month Visit	22	12
COMPLETED	22	12
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Placebo	Etanercept	Total
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months	Total of all reporting groups
Overall Participants	24	16	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 100%	16 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (8)	41 (9)	45 (9)
Sex: Female, Male (Count of Participants)
Female	12 50%	8 50%	20 50%
Male	12 50%	8 50%	20 50%
Region of Enrollment (participants) [Number]
United States	24 100%	16 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	C-reactive Protein (CRP)
Description	As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [Log10 mg/L]	0.61 (0.06)	0.68 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	treatment effect (etanercept vs. placebo) using ANCOVA including baseline CRP, age, and race
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Interleukin-6 (IL-6)
Description	6 month value of IL-6 (pg/mL)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [pg/mL]	8.2 (1.1)	11.3 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	within subject percent changes calculated for each timepoint and repeated measures ANCOVA controlling for age and race performed
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Repeated Measures ANCOVA
	Comments

3. Primary Outcome

Title	Adiponectin
Description	The ratio of circulating high molecular weight (HMW) adiponectin to total adiponectin ratio (HMW:total Adiponectin) at 6 months is reported.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [(ratio)]	0.30 (0.08)	0.40 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	within subject percent changes were calculated for each time point, then repeated measures ANCOVA controlling for age and race performed
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Repeated Measures ANCOVA
	Comments

4. Secondary Outcome

Title	Glucose Tolerance
Description	Fasting glucose (mg/dL) at 6mo
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [mg/dL]	95 (5)	91 (6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	percent change calculated then repeated measures ANCOVA performed controlling for age and race
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	repeated measures ANCOVA
	Comments

5. Secondary Outcome

Title	Endothelial Function
Description	Reactive Hyperemia Index (RHI) using peripheral artery tonometry (using Endo-PAT 2000). Peripheral artery tonometry measures blood flow in the tip of the index finger at baseline and in response to vaso-occlusion (inflated blood pressure cuff). The reactive hyperemia index is an index of vasodilation after occlusion compared to baseline. A higher value indicates better vasoreactivity. As this is a relatively new test, there are no thoroughly validated clinically utilized norms.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [(index)]	1.8 (0.11)	2.0 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	ANCOVA controlling for baseline value, age, race
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	White Blood Cell (WBC) Count
Description	Change in WBC during study (WBC at six months minus WBC at baseline)
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [th/cumm]	-0.17 (0.23)	-0.04 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Cardiac Echo Ejection Fraction (EF)
Description	change in EF (6mo - baseline). Please note that the value given is the absolute change in EF (which has units of percent), not the percent change in the variable.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [percent]	1.1 (0.7)	-1.1 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Body Composition
Description	6 month visceral adipose tissue (cm^2) - cross-sectional area of the visceral adipose tissue at the level of the 4th lumbar vertebrae was measured using single-slice abdominal computed tomography (CT) scan
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [cm^2]	206 (18)	186 (14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	ANCOVA controlling for baseline value, age, race
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Tumor Necrosis Factor (TNF) Receptor
Description	Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [pg/mL]	2573 (148)	4518 (329)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	within subject percent changes calculated then repeated measures ANCOVA controlling for age and race performed
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures ANCOVA
	Comments

10. Secondary Outcome

Title	Other Adipocytokines
Description	circulating resistin at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [ng/mL]	6.7 (0.5)	8.6 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	within subject percent changes calculated then repeated measures ANCOVA performed controlling for age and race
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Repeated Measures ANCOVA
	Comments

11. Secondary Outcome

Title	Lipid Levels
Description	total cholesterol (mg/dL) at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	22	12
Mean (Standard Error) [mg/dL]	196 (9)	201 (12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Etanercept
	Comments	ANCOVA controlling for baseline value, age, and race
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	ANCOVA
	Comments

12. Secondary Outcome

Title	Adipocyte Messenger Ribonucleic Acid (mRNA) Levels of Adipocytokines Including Tumor Necrosis Factor (TNF) -Alpha
Description	fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months	Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
Measure Participants	8	4
Mean (Standard Error) [fold-change]	2.3 (0.7)	1.1 (0.3)

Adverse Events

Time Frame	6 months
Arm/Group Title	Placebo		Etanercept
Arm/Group Description	Placebo injections, subcutaneously, twice weekly x 3 months, then once weekly x 3 months		Etanercept 50mg subcutaneously twice weekly x 3 months, then once weekly x 3 months
All Cause Mortality
	Placebo		Etanercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Etanercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		2/16 (12.5%)
Musculoskeletal and connective tissue disorders
Operative Surgical Procedure	1/24 (4.2%)	1	1/16 (6.3%)	1
Nervous system disorders
Paresthesia	0/24 (0%)	0	1/16 (6.3%)	1
Psychiatric disorders
Schizophrenia	1/24 (4.2%)	1	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Etanercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/24 (33.3%)		6/16 (37.5%)
Blood and lymphatic system disorders
Leukocytopenia	0/24 (0%)	0	1/16 (6.3%)	1
Gastrointestinal disorders
Diarrhea	1/24 (4.2%)	1	1/16 (6.3%)	1
General disorders
Foot Swelling	1/24 (4.2%)	1	0/16 (0%)	0
Infections and infestations
Dental Infection	1/24 (4.2%)	2	0/16 (0%)	0
Influenza	1/24 (4.2%)	1	0/16 (0%)	0
Upper respiratory infection	1/24 (4.2%)	1	2/16 (12.5%)	3
Musculoskeletal and connective tissue disorders
Bakers Cyst	1/24 (4.2%)	1	1/16 (6.3%)	1
Joint Pain	1/24 (4.2%)	1	0/16 (0%)	0
Nervous system disorders
Paresthesia	0/24 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Rash	1/24 (4.2%)	1	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

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.