Macrogol 3350-based Oral Osmotic Laxative in Preventing Cancer in Patients at Risk of Colorectal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00828984
• Collaborator: (none)
• Enrollment: 87
• Locations: 3
• Arms: 3
• Duration (Months): 60
• Patients Per Site: 29
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well macrogol 3350-based oral osmotic laxative (polyethylene glycol 3350) works in preventing cancer in patients at risk of colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of macrogol 3350-based oral osmotic laxative may stop cancer from growing in patients who are at risk of colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Adenomatous Polyp; Colorectal Carcinoma	Drug: macrogol 3350-based oral osmotic laxative; Other: Placebo; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8 g or 17 g/day for six months) versus placebo on epidermal growth factor receptor (EGFR) expression.

SECONDARY OBJECTIVES:

1. To determine the effect of PEG 3350 on aberrant crypt foci (ACF) number and to compare the reduction in ACF number between the low dose (8 g PEG 3350/day) and higher dose (17 g PEG 3350/day) groups.

2. To determine the effect of PEG 3350 on mucosal epithelial proliferation (marker of proliferation Ki-67 [Ki-67]).

3. To determine the effect of PEG 3350 on mucosal apoptosis (cleaved caspase-3).

4. To determine the effect of PEG 3350 on snail family zinc finger 1 (SNAIL) protein expression.

5. To determine the effect of PEG 3350 on messenger ribonucleic acid (mRNA) expression of SNAIL and EGFR.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: Patients receive high-dose macrogol 3350-based oral osmotic laxative orally (PO) once daily (QD).

ARM B: Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD.

ARM C: Patients receive placebo (i.e., maltodextrose powder) PO QD.

In all arms, treatment begins within 6-10 days after colonoscopy and continues for up to 6 months in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (high-dose PEG 3350) Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.	Drug: macrogol 3350-based oral osmotic laxative; Given PO; Other Names: Colonlytely ; Other: Laboratory Biomarker Analysis; Correlative studies
Experimental: Arm B (low-dose polyethylene glycol) Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.	Drug: macrogol 3350-based oral osmotic laxative; Given PO; Other Names: Colonlytely ; Other: Laboratory Biomarker Analysis; Correlative studies
Placebo Comparator: Arm C (placebo) Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.	Other: Placebo; Given PO; Other Names: PLCB ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Difference (After Treatment Minus Before Treatment) of EGFR Expression [6 months - baseline]

   Evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8g or 17g/day for six months) versus placebo on EGFR expression.

Secondary Outcome Measures

1. Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [6 months - baseline]

   To determine the effect of PEG 3350 on aberrant crypt foci (ACF) number and to compare the reduction in ACF number between the low dose (8g PEG 3350 / day) and higher dose (17g PEG 3350 / day) groups

2. Change in Ki-67 (Proliferation) Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [6 months - baseline]

   To determine the effect of PEG 3350 on mucosal epithelial proliferation (Ki-67)

3. Change in Mucosal Apoptosis (Cleaved Caspase-3) as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [6 months - baseline]

   Change in activated caspase-3 (apoptosis) expression as measured in endoscopically normal (non-ACF) mucosal biopsies

4. Change in SNAIL Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [6 months - baseline]

5. Change in E-cadherin Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [6 months - baseline]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• History of any size adenoma, known adenoma on present exam, or colon cancer within the last 6 years

• Scheduled for colonoscopy

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

• Willingness to forego PEG laxative during the study period; if the patient has been on a consistent dose of non-PEG laxative for 90 days prior to study entry, the participant may continue those laxatives; participants must agree to restrict additional laxative use to the rescue medication (bisacodyl) provided

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (equivalent to Karnofsky >= 70%)

• Leukocytes >= 3,000/uL

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• International normalized ratio (INR) =< 1.5

• Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X institutional ULN

• Estimated glomerular filtration rate (eGFR) > 45

• Blood urea nitrogen (BUN) < 40

• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; restricting intercourse to a surgically sterilized partner; abstinence) for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

• If patients are on a dose of cardioprotective aspirin, they must have been on a stable dose for three months prior to colonoscopy and agree to remain at that dose for the six months duration of the study; in addition, patients must agree to limit therapeutic nonsteroidal anti-inflammatory drug (NSAID) use (e.g. pain relief) to no more than 30 cumulative days during the six month duration of the trial

Exclusion Criteria:

• Average of > 2 bowel movements per day for the 90 days preceding study entry as assessed by self-report at baseline

• Average consistency of stools described as watery or loose for the 90 days preceding study entry as assessed by self-report at baseline

• Systemic chemotherapy for any cancer within 18 months prior to enrollment or evidence of active malignant disease

• Radiation to the rectum within 24 months prior to enrollment

• Polyethylene glycol use within 3 months of enrollment (except as part of colonoscopy preparation)

• Systemic corticosteroid use

• Anticoagulant therapy

• Inflammatory bowel disease

• Removal of the rectum

• Evidence of proctitis (radiation, inflammatory bowel disease [IBD], infectious, etc.) by history or endoscopy

• Other investigational agent use within 30 days prior to enrollment

• History of adverse reactions attributed to compounds of similar chemical or biologic composition to polyethylene glycol, bisacodyl or methylene blue

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnancy

• Patient must not have used suppository medication or enemas for the three months prior to the trial or for the duration of the trial except as directed for colonoscopy or flexible sigmoidoscopy procedure bowel preparation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637
2	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
3	Boston Medical Center	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Seema Khan, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00828984
• Other Study ID Numbers: NCI-2009-01113; NCI-2009-01113; NCI 06-8-01; CDR0000632553; N01CN35157; NCI06-8-01; NWU06-8-01; P30CA060553
• First Posted: Jan 26, 2009
• Last Update Posted: Apr 18, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Colorectal Neoplasms; Adenomatous Polyps; Laxatives; Polyethylene glycol 3350

Study Results

Participant Flow

Recruitment Details	Age 18 and older; Recruitment sites: NorthShore University HealthSystem, University of Chicago, Boston University (no accrual occurred)
Pre-assignment Detail	History of any size adenoma or colon cancer within the last 6 years;

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	28	31	28
Randomization	28	31	28
Treatment	24	26	24
Flexible Sigmoidoscopy	20	19	19
Post Intervention Follow-Up	15	16	19
COMPLETED	14	15	19
NOT COMPLETED	14	16	9

Baseline Characteristics

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)	Total
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies	Total of all reporting groups
Overall Participants	28	31	28	87
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	19 67.9%	18 58.1%	18 64.3%	55 63.2%
>=65 years	9 32.1%	13 41.9%	10 35.7%	32 36.8%
Sex: Female, Male (Count of Participants)
Female	14 50%	17 54.8%	12 42.9%	43 49.4%
Male	14 50%	14 45.2%	16 57.1%	44 50.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%	2 6.5%	0 0%	3 3.4%
Not Hispanic or Latino	27 96.4%	29 93.5%	28 100%	84 96.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	2 7.1%	2 2.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 14.3%	5 16.1%	0 0%	9 10.3%
White	24 85.7%	26 83.9%	26 92.9%	76 87.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Difference (After Treatment Minus Before Treatment) of EGFR Expression
Description	Evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8g or 17g/day for six months) versus placebo on EGFR expression.
Time Frame	6 months - baseline

Outcome Measure Data

Analysis Population Description

The study population includes men and women of all races and ethnicities who are scheduled to undergo colonoscopy for a history of colonic neoplasia (within the past 6 years of either colonic adenoma ≥ 5 mm or carcinoma).

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	15	19
Mean (Standard Deviation) [ng/ml]	0.17 (1.07)	-0.40 (0.66)	0.21 (0.67)

2. Secondary Outcome

Title	Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Description	To determine the effect of PEG 3350 on aberrant crypt foci (ACF) number and to compare the reduction in ACF number between the low dose (8g PEG 3350 / day) and higher dose (17g PEG 3350 / day) groups
Time Frame	6 months - baseline

Outcome Measure Data

Analysis Population Description

The study population includes men and women of all races and ethnicities who are scheduled to undergo colonoscopy for a history of colonic neoplasia (within the past 6 years of either colonic adenoma ≥ 5 mm or carcinoma).

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	15	19
Mean (Standard Deviation) [Aberrant Crypt Foci]	2.11 (4.63)	1 (1.73)	-0.73 (2.74)

3. Secondary Outcome

Title	Change in Ki-67 (Proliferation) Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Description	To determine the effect of PEG 3350 on mucosal epithelial proliferation (Ki-67)
Time Frame	6 months - baseline

Outcome Measure Data

Analysis Population Description

To determine the effect of PEG 3350 on aberrant crypt foci (ACF) number and to compare the reduction in ACF number between the low dose (8g PEG 3350 / day) and higher dose (17g PEG 3350 / day) groups.

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	15	19
Mean (Standard Deviation) [ng/ml]	2.74 (5.20)	-0.86 (6.62)	-3.58 (11.84)

4. Secondary Outcome

Title	Change in Mucosal Apoptosis (Cleaved Caspase-3) as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Description	Change in activated caspase-3 (apoptosis) expression as measured in endoscopically normal (non-ACF) mucosal biopsies
Time Frame	6 months - baseline

Outcome Measure Data

Analysis Population Description

The study population includes men and women of all races and ethnicities who are scheduled to undergo colonoscopy for a history of colonic neoplasia (within the past 6 years of either colonic adenoma ≥ 5 mm or carcinoma).

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	15	19
Mean (Standard Deviation) [ng/ml]	-0.27 (2.97)	0.25 (3.18)	-0.15 (2.3)

5. Secondary Outcome

Title	Change in SNAIL Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Time Frame	6 months - baseline

Outcome Measure Data

Analysis Population Description

The study population includes men and women of all races and ethnicities who are scheduled to undergo colonoscopy for a history of colonic neoplasia (within the past 6 years of either colonic adenoma ≥ 5 mm or carcinoma).

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	15	19
Mean (Standard Deviation) [ng/ml]	0.45 (0.58)	0.55 (0.88)	0.08 (0.70)

6. Secondary Outcome

Title	Change in E-cadherin Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Time Frame	6 months - baseline

Outcome Measure Data

Analysis Population Description

The study population includes men and women of all races and ethnicities who are scheduled to undergo colonoscopy for a history of colonic neoplasia (within the past 6 years of either colonic adenoma ≥ 5 mm or carcinoma).

Arm/Group Title	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	14	15	19
Mean (Standard Deviation) [ng/ml]	-0.17 (1.75)	0.15 (0.59)	-0.18 (0.82)

Adverse Events

Time Frame	6 months
Arm/Group Title	Arm A (High-dose PEG 3350)		Arm B (Low-dose Polyethylene Glycol)		Arm C (Placebo)
Arm/Group Description	Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 17g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies		Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. 8g day/macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies		Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Arm A (High-dose PEG 3350)		Arm B (Low-dose Polyethylene Glycol)		Arm C (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A (High-dose PEG 3350)		Arm B (Low-dose Polyethylene Glycol)		Arm C (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		1/31 (3.2%)		2/28 (7.1%)
Blood and lymphatic system disorders
Hemorrgae/Bleeding,CNS	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Gastrointestinal disorders
Perforation,GI: Colon	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Infections and infestations
Infection - Other	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Arm A (High-dose PEG 3350)		Arm B (Low-dose Polyethylene Glycol)		Arm C (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/28 (46.4%)		16/31 (51.6%)		13/28 (46.4%)
Blood and lymphatic system disorders
Edema; Limb	0/28 (0%)	0	1/31 (3.2%)	1	1/28 (3.6%)	1
Hemorrhage, GI: Rectum	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Cardiac disorders
Cardiac arrythmia: Supraventricular and nodal arrhythmia: Atrial fibrillation	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Ear and labyrinth disorders
Tinnitus	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Otitis, Middle Ear (Non-Infectious)	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Otitis, External Ear (Non-Infectious)	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Endocrine disorders
Endocrine - Other (Specify, __)	8/28 (28.6%)	17	1/31 (3.2%)	1	0/28 (0%)	0
Gastrointestinal disorders
Diarrhea	8/28 (28.6%)	8	4/31 (12.9%)	5	4/28 (14.3%)	5
Flatulence	2/28 (7.1%)	8	2/31 (6.5%)	2	3/28 (10.7%)	4
Distention/bloating, Abdominal	6/28 (21.4%)	13	3/31 (9.7%)	4	3/28 (10.7%)	5
Heartburn/Dyspepsia	0/28 (0%)	0	1/31 (3.2%)	2	0/28 (0%)	0
Constipation	0/28 (0%)	0	2/31 (6.5%)	2	0/28 (0%)	0
Vomiting	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Nausea	1/28 (3.6%)	1	0/31 (0%)	0	1/28 (3.6%)	1
Gastrointestinal - Other (Specify)	2/28 (7.1%)	2	0/31 (0%)	0	0/28 (0%)	0
General disorders
Pain: Pain Nos	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Pain - Other (Specify, __)	0/28 (0%)	0	1/31 (3.2%)	4	0/28 (0%)	0
Pain: Muscle	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Pain: Abdomen Nos	2/28 (7.1%)	6	1/31 (3.2%)	1	4/28 (14.3%)	6
Pain: Joint	0/28 (0%)	0	1/31 (3.2%)	2	2/28 (7.1%)	8
Pain: Neuralgia/Peripheral Nerve	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Pain: Throat/Pharynx/Larynx	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Pain: Stomach	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Pain: Rectum	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Pain: Chest/Thorax Nos	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Pain: Back	1/28 (3.6%)	1	0/31 (0%)	0	1/28 (3.6%)	1
Pain: Dental/Teeth/Peridontal	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Pain: Headache	1/28 (3.6%)	1	0/31 (0%)	0	0/28 (0%)	0
"Constitutional Symptoms: Fever (In the absence of Neutropenia, where Neutropenia is defined as ANC	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Constitutional Symptoms: Fatigue (Asthenia, Lethargy, Malaise)	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Syndromes: Flu-like Syndrome	0/28 (0%)	0	2/31 (6.5%)	6	0/28 (0%)	0
Immune system disorders
Allergic Rhinitis (Including sneezing, nasal stuffiness, postnasal drip)	0/28 (0%)	0	2/31 (6.5%)	2	2/28 (7.1%)	2
Infections and infestations
Infection with normal ANC or Grade 1 or 2 Neutrophils: Nerve-Peripheral	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Infection with unknown ANC: Upper Airway Nos	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Infection - Other (Specify, __)	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Infection with unknown ANC: Pharynx	0/28 (0%)	0	1/31 (3.2%)	1	1/28 (3.6%)	1
Infection with normal ANC or Grade 1 or 2 Neutrophils: Upper Airway Nos	0/28 (0%)	0	1/31 (3.2%)	1	1/28 (3.6%)	2
Infection with unknown ANC: Skin (Cellulitis)	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
"Infection (documented clinically or microbiologically) with grade 3 or 4 neutrophils (ANC <1.0 X 1	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Infection with unknown ANC: Nerve-Peripheral	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Infection with unknown ANC: Dental-tooth	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Infection with unknown ANC: Sinus	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	1
Infection with unknown ANC: Bladder (Urinary)	1/28 (3.6%)	1	0/31 (0%)	0	0/28 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft tissue - Other (Specify, __)	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Musculoskeletal/Soft tissue - Arthritis (non-septic)	0/28 (0%)	0	0/31 (0%)	0	2/28 (7.1%)	2
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory: Nasal Cavity/Paranasal Sinus Reactions	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Pulmonary/Upper Respiratory: Cough	0/28 (0%)	0	2/31 (6.5%)	2	0/28 (0%)	0
Skin and subcutaneous tissue disorders
Rash/Desquamation	0/28 (0%)	0	1/31 (3.2%)	1	0/28 (0%)	0
Dry Skin	0/28 (0%)	0	0/31 (0%)	0	1/28 (3.6%)	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.