Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial

• Sponsor: Joseph Roscoe (Other)
• Overall Status: Completed
• CT.gov ID: NCT00475085
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1,021
• Locations: 16
• Arms: 4
• Patients Per Site: 63.8

Study Details

Study Description

Brief Summary

RATIONALE: Antiemetic drugs, such as granisetron, dexamethasone, prochlorperazine, aprepitant, and palonosetron, may help lessen or prevent nausea. It is not yet known which combination of antiemetic drugs is more effective in preventing nausea caused by chemotherapy.

PURPOSE: This randomized phase III trial is comparing different combinations of granisetron, dexamethasone, prochlorperazine, aprepitant, and palonosetron to see how well they work in preventing nausea in patients undergoing chemotherapy for breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Nausea	Drug: aprepitant; Drug: dexamethasone; Drug: granisetron hydrochloride; Drug: palonosetron hydrochloride; Drug: prochlorperazine; Drug: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of palonosetron hydrochloride and dexamethasone followed by prochlorperazine with vs without dexamethasone in preventing delayed nausea in women with chemotherapy-naive breast cancer. (Arms I and IV)

• Determine if palonosetron hydrochloride is more effective than granisetron hydrochloride in controlling treatment-related delayed nausea in these patients. (Arms I and II)

• Determine if the currently recommended antiemetic guideline of aprepitant combined with palonosetron hydrochloride and dexamethasone is the most effective antiemetic regimen for controlling treatment-related delayed nausea in these patients. (Arms III and IV)

Secondary

• Determine if the addition of dexamethasone to prochlorperazine is more effective than the same regimen without dexamethasone for reducing interference with functioning caused by chemotherapy-induced nausea and vomiting in these patients. (Arms I and IV)

• Determine if palonosetron hydrochloride is more effective than granisetron hydrochloride for reducing interference with functioning caused by chemotherapy-induced nausea and vomiting in these patients. (Arms I and II)

• Determine if the currently recommended antiemetic guideline of aprepitant combined with palonosetron hydrochloride and dexamethasone is the most effective antiemetic regimen for reducing interference with functioning due to chemotherapy-induced nausea and vomiting in these patients. (Arms III and IV)

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to CCOP center and gender. Patients are randomized to 1 of 4 treatment arms. Patients receive study treatment approximately 30 minutes before their scheduled first chemotherapy treatment.

• Arm I: Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.

• Arm II: Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.

• Arm III: Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3.

• Arm IV: Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3.

Quality of life is assessed at baseline and on day 4. Nausea and vomiting, fatigue, sleep quality, exercise, and the need for rescue medication (metoclopramide) are assessed on days 1-4.

PROJECTED ACCRUAL: A total of 890 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1021 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.	Drug: dexamethasone; Given orally or IV; Other Names: Decadron ; Drug: palonosetron hydrochloride; Given orally or IV; Other Names: Aloxi ; Drug: prochlorperazine; Given orally or IV; Other Names: Compazine ; Drug: placebo; Given orally
Experimental: Arm II Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.	Drug: dexamethasone; Given orally or IV; Other Names: Decadron ; Drug: granisetron hydrochloride; Given orally or IV; Other Names: Kytril ; Drug: prochlorperazine; Given orally or IV; Other Names: Compazine ; Drug: placebo; Given orally
Active Comparator: Arm III Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3.	Drug: aprepitant; Given orally or IV; Other Names: Emend ; Drug: dexamethasone; Given orally or IV; Other Names: Decadron ; Drug: palonosetron hydrochloride; Given orally or IV; Other Names: Aloxi ; Drug: placebo; Given orally
Experimental: Arm IV Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3.	Drug: dexamethasone; Given orally or IV; Other Names: Decadron ; Drug: palonosetron hydrochloride; Given orally or IV; Other Names: Aloxi ; Drug: prochlorperazine; Given orally or IV; Other Names: Compazine ; Drug: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Home Record: Severity of Delayed Nausea [average of day 1 afternoon, evening and night, and all of days 2 and 3]

   1=not at all nauseated to 7=extremely nauseated, therefore higher values are worse

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Have a diagnosis of cancer and be chemotherapy naive.

• Must be scheduled to receive a chemotherapy treatment containing doxorubicin hydrochloride, epirubicin hydrochloride, cisplatin, carboplatin, or oxaliplatin (any dose or schedule) without concurrent radiotherapy or interferon treatment

• Chemotherapy may be for adjuvant, neoadjuvant, curative or palliative intent.

• Dose-dense regimens (e.g. chemotherapy with doxorubicin or epirubicin given every two weeks)are allowed.

• For the purposes of this study, Day 1 of chemotherapy will be defined as the day of administration of cisplatin, carboplatin, oxaliplatin, doxorubicin or epirubicin.

• Regimens with multiple-day doses of doxorubicin, epirubicin, cisplatin, carboplatin, oxaliplatin, dacarbazine, hexamethylmelamine, nitrosoureas, or streptozocin are not allowed. Chemotherapy agents, other than those listed above, may be given orally, intravenously, or by continuous infusion on one or multiple days.

• Able to understand English

Exclusion criteria:

• No symptomatic brain metastases

• No concurrent or impending bowel obstruction

• Regimens containing liposomal doxorubicin or cisplatin are not allowed.

• No concurrent pimozide, terfenadine, astemizole, or cisapride

• No concurrent doxorubicin hydrochloride liposome or cisplatin

• No concurrent multiple-day doses of dacarbazine, altretamine, nitrosoureas, streptozocin, cisplatin, carboplatin, or oxaliplatin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - Gulf Coast	Mobile	Alabama	United States	36695
2	CCOP - Central Illinois	Decatur	Illinois	United States	62526
3	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
4	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
5	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
6	CCOP - Metro-Minnesota	St. Louis Park	Minnesota	United States	55416
7	CCOP - Kansas City	Kansas City	Missouri	United States	64131
8	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
9	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
10	CCOP - North Shore University Hospital	Manhassett	New York	United States	11030
11	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
12	CCOP - Columbus	Columbus	Ohio	United States	43215
13	CCOP - Dayton	Dayton	Ohio	United States	45429
14	CCOP - Greenville	Greenville	South Carolina	United States	29615
15	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
16	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• Joseph Roscoe
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Joseph A. Roscoe, PhD, James P. Wilmot Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joseph Roscoe, Research Associate Professor, University of Rochester NCORP Research Base
• ClinicalTrials.gov Identifier: NCT00475085
• Other Study ID Numbers: CDR0000544841; U10CA037420; URCC-U1105
• First Posted: May 17, 2007
• Last Update Posted: Nov 10, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Joseph Roscoe, Research Associate Professor, University of Rochester NCORP Research Base: nausea and vomiting; recurrent breast cancer; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; inflammatory breast cancer; male breast cancer
• Additional relevant MeSH terms: Nausea; Dexamethasone; Aprepitant; Palonosetron; Granisetron; Prochlorperazine

Study Results

Participant Flow

Recruitment Details	Patients from 15 private-practice oncology groups in the USA affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program (URCC CCOP)were enrolled by research personnel from May 2007 to September 2010.

Arm/Group Title	Arm 1 Palonosetron, Dexamethasone, Compazine	Arm 2 Granisetron, Dexamethasone, Compazine	Arm 3 Aprepitant, Palonosetron, Dexamethasone	Arm 4 Palonosetron, Dexamethasone, Compazine, Dexamethasone
Arm/Group Description	Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV granisetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3. placebo : Given orally aprepitant : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV
Period Title: Overall Study
STARTED	253	254	260	254
COMPLETED	235	234	241	234
NOT COMPLETED	18	20	19	20

Baseline Characteristics

Arm/Group Title	Arm II	Arm III	Arm I	Arm IV	Total
Arm/Group Description	Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV granisetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3. placebo : Given orally aprepitant : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Total of all reporting groups
Overall Participants	254	260	254	253	1021
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.2 (12.7)	58.6 (11.4)	57.1 (12.4)	58.2 (11.4)	57.8 (12.0)
Sex: Female, Male (Count of Participants)
Female	208 81.9%	201 77.3%	193 76%	208 82.2%	810 79.3%
Male	46 18.1%	59 22.7%	61 24%	45 17.8%	211 20.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.8%	2 0.8%	3 1.2%	2 0.8%	9 0.9%
Asian	2 0.8%	4 1.5%	0 0%	2 0.8%	8 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 0.4%	1 0.1%
Black or African American	18 7.1%	28 10.8%	20 7.9%	19 7.5%	85 8.3%
White	232 91.3%	226 86.9%	231 90.9%	229 90.5%	918 89.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	254 100%	260 100%	254 100%	253 100%	1021 100%
Previous Surgery (participants) [Number]
Number [participants]	193 76%	194 74.6%	196 77.2%	198 78.3%	781 76.5%
Previous Radiotherapy (participants) [Number]
Number [participants]	6 2.4%	12 4.6%	12 4.7%	9 3.6%	39 3.8%

Outcome Measures

1. Primary Outcome

Title	Home Record: Severity of Delayed Nausea
Description	1=not at all nauseated to 7=extremely nauseated, therefore higher values are worse
Time Frame	average of day 1 afternoon, evening and night, and all of days 2 and 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II	Arm III	Arm I	Arm IV
Arm/Group Description	Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV granisetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3. placebo : Given orally aprepitant : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV	Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV
Measure Participants	234	241	234	235
Mean (Standard Deviation) [units on a scale]	1.88 (1.27)	1.65 (1.15)	1.87 (1.20)	1.68 (1.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II, Arm I
	Comments	Group 1 - Group 2 (palonosetron vs. granisetron)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.718
	Comments	Response skewed. P-value determined after Box-Cox transformation (lambda=-1.6). Significance level set to 0.017 to account for three tested hypotheses.
	Method	ANOVA
	Comments	Testing and estimation performed using contrasts in the context of an omnibus ANOVA.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.013
	Confidence Interval	(2-Sided) 95%; -0.225 to 0.200
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm IV
	Comments	Group 1 - Group 4 (adding dexamethasone)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	Response skewed. P-value determined after Box-Cox transformation (lambda=-1.6). Significance level set to 0.017 to account for three tested hypotheses.
	Method	ANOVA
	Comments	Testing and estimation performed using contrasts in the context of an omnibus ANOVA.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.195
	Confidence Interval	(2-Sided) 95%; -0.017 to 0.407
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm III, Arm IV
	Comments	Group 3 - Group 4 (aprepitant vs. prochlorperazine)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.557
	Comments	Response skewed. P-value determined after Box-Cox transformation (lambda=-1.6). Significance level set to 0.017 to account for three tested hypotheses.
	Method	ANOVA
	Comments	Testing and estimation performed using contrasts in the context of an omnibus ANOVA.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.025
	Confidence Interval	(2-Sided) 95%; -0.236 to 0.186
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Arm II		Arm III		Arm I		Arm IV
Arm/Group Description	Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV granisetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV		Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3. placebo : Given orally aprepitant : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV		Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV		Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3. placebo : Given orally prochlorperazine : Given orally or IV palonosetron hydrochloride : Given orally or IV dexamethasone : Given orally or IV
All Cause Mortality
	Arm II		Arm III		Arm I		Arm IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm II		Arm III		Arm I		Arm IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/ (NaN)		17/ (NaN)		16/ (NaN)		11/ (NaN)
Blood and lymphatic system disorders
Lymphoma	1/254 (0.4%)	1	0/260 (0%)	0	0/254 (0%)	0	0/253 (0%)	0
Neutropenia	0/254 (0%)	0	3/260 (1.2%)	3	1/254 (0.4%)	1	0/253 (0%)	0
Pancytopenia	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	0/253 (0%)	0
Trombocytopenia	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Gastrointestinal disorders
Gastrointestinal	1/254 (0.4%)	1	3/260 (1.2%)	3	0/254 (0%)	0	3/253 (1.2%)	3
GI Bleed	0/254 (0%)	0	0/260 (0%)	0	0/254 (0%)	0	1/253 (0.4%)	1
Nausea/Vomiting	1/254 (0.4%)	1	1/260 (0.4%)	1	1/254 (0.4%)	1	3/253 (1.2%)	4
General disorders
Chest Pain	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	1/253 (0.4%)	1
Dehydration	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	0/253 (0%)	0
Edema	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	0/253 (0%)	0
Fatigue	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	0/253 (0%)	0
Headache	1/254 (0.4%)	1	0/260 (0%)	0	2/254 (0.8%)	2	0/253 (0%)	0
Migraine	0/254 (0%)	0	0/260 (0%)	0	0/254 (0%)	0	1/253 (0.4%)	2
Restless	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Immune system disorders
Allergic Reaction	0/254 (0%)	0	2/260 (0.8%)	2	1/254 (0.4%)	1	0/253 (0%)	0
Infections and infestations
Infection	0/254 (0%)	0	0/260 (0%)	0	2/254 (0.8%)	2	0/253 (0%)	0
MRSA	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Injury, poisoning and procedural complications
Infusion Reaction	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Renal and urinary disorders
Renal Failure	1/254 (0.4%)	1	1/260 (0.4%)	1	0/254 (0%)	0	1/253 (0.4%)	1
Reproductive system and breast disorders
Hydrocele	0/254 (0%)	0	0/260 (0%)	0	1/254 (0.4%)	1	0/253 (0%)	0
Respiratory, thoracic and mediastinal disorders
COPD	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	0/253 (0%)	0
Pleural Effusion	0/254 (0%)	0	1/260 (0.4%)	1	2/254 (0.8%)	2	0/253 (0%)	0
Pneumonia	1/254 (0.4%)	1	0/260 (0%)	0	0/254 (0%)	0	0/253 (0%)	0
Vascular disorders
Hemorrhage	0/254 (0%)	0	0/260 (0%)	0	0/254 (0%)	0	1/253 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Arm II		Arm III		Arm I		Arm IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		1/ (NaN)		0/ (NaN)		1/ (NaN)
Gastrointestinal disorders
Gastrointestinal	0/254 (0%)	0	0/260 (0%)	0	0/254 (0%)	0	1/253 (0.4%)	1
General disorders
Chest Pain	0/254 (0%)	0	1/260 (0.4%)	1	0/254 (0%)	0	0/253 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary	1/254 (0.4%)	1	0/260 (0%)	0	0/254 (0%)	0	0/253 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.