A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism (VTE) Prophylaxis in Ambulatory Cancer Participants

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02555878
• Collaborator: Bayer (Industry)
• Enrollment: 841
• Locations: 158
• Arms: 2
• Actual Duration (Months): 35.4
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate that rivaroxaban is superior to placebo for reducing the risk of the primary composite outcome as defined by objectively confirmed symptomatic lower extremity proximal deep vein thrombosis (DVT), asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal pulmonary embolism (PE), incidental PE, and venous thromboembolism (VTE)-related death in ambulatory adult participants with various cancer types receiving systemic cancer therapy who are at high risk of developing a VTE.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Rivaroxaban; Drug: Placebo	Phase 3

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, superiority study comparing the efficacy and safety of rivaroxaban with placebo for primary prophylaxis of venous thromboembolism (VTE) in ambulatory adult participants, with various cancer types who are scheduled to initiate systemic cancer therapy. The study consists of 3 Phases: Screening Phase (14 Days), double-blind treatment Phase (180 Days) and follow up Phase (30 Days). The duration of participation in the study for each participant is approximately 32 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 841 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Efficacy and Safety of Rivaroxaban Prophylaxis Compared With Placebo in Ambulatory Cancer Patients Initiating Systemic Cancer Therapy and at High Risk for Venous Thromboembolism
• Actual Study Start Date: Sep 11, 2015
• Actual Primary Completion Date: Aug 24, 2018
• Actual Study Completion Date: Aug 24, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban Participants will be administered rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.	Drug: Rivaroxaban; Rivaroxaban 10 milligram (mg) tablet will be administered orally once daily for 180 days.
Experimental: Placebo Participants will be administered matching placebo tablet orally once daily for 180 days.	Drug: Placebo; Placebo tablet will be administered orally once daily for 180 days.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Time to First Occurrence of Primary Efficacy Endpoint (Composite and Components) [Up to Day 180]

   Percentage of participants with time to the first occurrence of primary efficacy endpoint (composite and components) was reported. The primary efficacy composite endpoint is time to first occurrence of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, or VTE-related death as adjudicated by an independent blinded Clinical Endpoint Committee (CEC).

2. Percentage of Participants With Time to the First Occurrence of Major Bleeding Events as Defined by International Society of Thrombosis and Haemostasis (ISTH) [From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)]

   Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.

Secondary Outcome Measures

1. Percentage of Participants With Time to the First Occurrence of Symptomatic VTE Events or VTE-Related Deaths [Up to Day 180]

   Percentage of participants with time to first occurrence of the composite endpoint of symptomatic VTE events (symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, or symptomatic non-fatal PE) or VTE related deaths as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

2. Percentage of Participants With All-Cause Mortality [Up to Day 180]

   Percentage of participants with all-cause mortality as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. Overall deaths occurred during observation period (defined by start to end date of the observation period [that is approximately 180 days] are reported here.

3. Percentage of Participants With Time to the First Occurrence of Fatal or Non-fatal Arterial Thromboembolic Events (ATE) [Up to Day 180]

   Percentage of participants with time to first occurrence of fatal/non-fatal ATE (a composite of occurrence of myocardial infarction (MI), stroke [ischemic infarction with or without hemorrhagic conversion or primary hemorrhagic events - intraparenchymal hemorrhage, subdural hematoma or epidural hematoma] or any other ATE recorded) event as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

4. Percentage of Participants With Time to the First Occurrence of Fatal or Non-fatal Visceral VTE [Up to Day 180]

   Percentage of participants with time to the first occurrence of fatal or non-fatal visceral VTE as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

5. Percentage of Participants With Time to the First Occurrence of Composite Efficacy Endpoint 1 [Up to Day 180]

   Percentage of participants with time to first occurrence of composite efficacy endpoint 1 (composite of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE or all-cause mortality) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

6. Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 2 [Up to Day 180]

   Percentage of participants with time to first occurrence of composite efficacy endpoint 2 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE or VTE-related deaths) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

7. Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 3 [Up to Day 180]

   Percentage of participants with time to first occurrence of composite efficacy endpoint 3 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, asymptomatic lower extremity proximal DVT, symptomatic non-fatal PE, incidental PE, VTE-related deaths, fatal/non-fatal ATE [MI, stroke {ischemic infarction with or without hemorrhagic conversion or primary hemorrhagic events - intraparenchymal hemorrhage, subdural hematoma or epidural hematoma} or any ATE] or fatal/non-fatal visceral VTE) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

8. Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 4 [Up to Day 180]

   Percentage of participants with time to first occurrence of composite efficacy endpoint 4 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, VTE-related deaths or major bleeding events up to Day 180) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.

9. Percentage of Participants With Time to the First Occurrence of Clinically Relevant Non-major Bleeding [From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)]

   Percentage of participants with time to the first occurrence of clinically relevant non-major bleeding was reported. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, or unscheduled contact with a physician, or temporary cessation of study treatment, or discomfort such as pain, or impairment of activities of daily life.

10. Percentage of Participants With Time to the First Occurrence of Minor Bleeding [From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)]

    Percentage of participants with time to the first occurrence of minor bleeding was reported. Minor bleeding (that is, minimal bleeding) is defined as overt bleeding episodes not meeting the criteria for major or clinically relevant non-major bleeding event.

11. Percentage of Participants With Time to the First Occurrence of Any Bleeding [From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)]

    Percentage of participants with time to the first occurrence of any bleeding event was reported. Any bleeding is defined as a composite of major bleeding, clinically relevant non-major bleeding, or minor bleeding.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have histologically confirmed solid malignancy including but not limited to: pancreas, lung, stomach, colon, rectum, bladder, breast, ovary, renal or lymphoma (hematologic), with locally advanced or metastatic disease

• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

• Have a Khorana thromboembolic risk Score greater than or equal to (>=) 2

• Creatinine clearance (CrCl) >= 30 milliliter per minute (mL/min)

• Plan to initiate systemic cancer therapy within plus or minus (+-) 1 week of receiving the first dose of study drug with the intention of receiving systemic cancer therapy during the double-blind treatment period for an intended duration determined by the treating oncologist according to standard protocols of clinical care

Exclusion Criteria:

• Diagnosis of primary brain tumors

• Known history of brain metastases

• Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding

• Hematologic malignancies with the exception of lymphoma

• Platelet count less than (<) 50,000/millimeter^{3 (mm}3), Life expectancy of less than or equal to (<=) 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States
2		Tucson	Arizona	United States
3		Little Rock	Arkansas	United States
4		Los Angeles	California	United States
5		Martinez	California	United States
6		Santa Barbara	California	United States
7		Torrance	California	United States
8		Upland	California	United States
9		Denver	Colorado	United States
10		Norwich	Connecticut	United States
11		Gainesville	Florida	United States
12		Miami Shores	Florida	United States
13		Miami	Florida	United States
14		New Port Richey	Florida	United States
15		Atlanta	Georgia	United States
16		Evanston	Illinois	United States
17		Joliet	Illinois	United States
18		Peoria	Illinois	United States
19		Rockford	Illinois	United States
20		Skokie	Illinois	United States
21		Urbana	Illinois	United States
22		Anderson	Indiana	United States
23		Cedar Rapids	Iowa	United States
24		Brewer	Maine	United States
25		Baltimore	Maryland	United States
26		Silver Spring	Maryland	United States
27		Boston	Massachusetts	United States
28		Detroit	Michigan	United States
29		Rochester	Minnesota	United States
30		Saint Cloud	Minnesota	United States
31		Kansas City	Missouri	United States
32		Grand Island	Nebraska	United States
33		Las Vegas	Nevada	United States
34		Lebanon	New Hampshire	United States
35		Albany	New York	United States
36		Bronx	New York	United States
37		East Syracuse	New York	United States
38		New York	New York	United States
39		Rochester	New York	United States
40		Charlotte	North Carolina	United States
41		High Point	North Carolina	United States
42		Cleveland	Ohio	United States
43		Eugene	Oregon	United States
44		Portland	Oregon	United States
45		Erie	Pennsylvania	United States
46		Charleston	South Carolina	United States
47		Greenville	South Carolina	United States
48		North Charleston	South Carolina	United States
49		Rapid City	South Dakota	United States
50		Nashville	Tennessee	United States
51		Abilene	Texas	United States
52		Austin	Texas	United States
53		Beaumont	Texas	United States
54		Bedford	Texas	United States
55		Dallas	Texas	United States
56		Denton	Texas	United States
57		Flower Mound	Texas	United States
58		Garland	Texas	United States
59		Houston	Texas	United States
60		Paris	Texas	United States
61		San Antonio	Texas	United States
62		Sugar Land	Texas	United States
63		Temple	Texas	United States
64		The Woodlands	Texas	United States
65		Tyler	Texas	United States
66		Waco	Texas	United States
67		Roanoke	Virginia	United States
68		Winchester	Virginia	United States
69		Green Bay	Wisconsin	United States
70		Weston	Wisconsin	United States
71		Amberloup		Belgium
72		Bonheiden		Belgium
73		Brussel		Belgium
74		Bruxelles		Belgium
75		Edegem		Belgium
76		Laken (brussel)		Belgium
77		Turnhout		Belgium
78		Wilrijk		Belgium
79		Barretos		Brazil
80		Caxias do Sul		Brazil
81		Curitiba		Brazil
82		Itajai		Brazil
83		Lajeado		Brazil
84		Londrina		Brazil
85		Mogi das Cruzes		Brazil
86		Porto Alegre, Rs		Brazil
87		Porto Alegre		Brazil
88		Rio de Janeiro		Brazil
89		Santo André		Brazil
90		Sao Jose do Rio Preto		Brazil
91		Sao Paulo		Brazil
92		Sorocaba		Brazil
93		São Paulo		Brazil
94		Plovdiv N/a		Bulgaria
95		Plovdiv		Bulgaria
96		Sofia		Bulgaria
97		Toronto	Ontario	Canada
98		Saint-Jerome	Quebec	Canada
99		Quebec		Canada
100		Benesov Nad Cernou		Czechia
101		Brno		Czechia
102		Jindrichuv Hradec		Czechia
103		Kladno		Czechia
104		Liberec		Czechia
105		Novy Jicin		Czechia
106		Olomouc		Czechia
107		Pardubice		Czechia
108		Praha 4		Czechia
109		Praha 5		Czechia
110		Tabor		Czechia
111		Angers Cedex 9		France
112		Angers		France
113		Avignon Cedex 9		France
114		Dijon Cedex		France
115		Hyers		France
116		Le Mans Cedex 2		France
117		Le Mans cedex 9		France
118		Paris		France
119		Rennes Cedex		France
120		Saint Herblain		France
121		Valenciennes		France
122		Berlin		Germany
123		Brandenburg		Germany
124		Dortmund		Germany
125		Dresden		Germany
126		Esslingen		Germany
127		Gauting		Germany
128		Hamburg		Germany
129		Hannover		Germany
130		Herne		Germany
131		Kiel		Germany
132		Koeln		Germany
133		Leipzig		Germany
134		Luebeck		Germany
135		Magdeburg		Germany
136		Merseburg		Germany
137		Minden		Germany
138		München		Germany
139		Paderborn		Germany
140		Recklinghausen		Germany
141		Weiden		Germany
142		Arkhangelsk		Russian Federation
143		Chelyabinsk		Russian Federation
144		Kursk		Russian Federation
145		Moscow		Russian Federation
146		Novosibirsk		Russian Federation
147		Omsk		Russian Federation
148		Saint Petersburg		Russian Federation
149		St Petersburg		Russian Federation
150		Tomsk		Russian Federation
151		Yaroslavi		Russian Federation
152		Bournemouth		United Kingdom
153		Cheltenham		United Kingdom
154		Dundee		United Kingdom
155		London		United Kingdom
156		Manchester		United Kingdom
157		Plymouth		United Kingdom
158		Swindon		United Kingdom

Sponsors and Collaborators

• Janssen Research & Development, LLC
• Bayer

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Statistical Analysis Plan - Sep 5, 2018
• Study Protocol - Feb 16, 2018

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02555878
• Other Study ID Numbers: CR107047; 39039039STM4001; 2015-001630-21
• First Posted: Sep 22, 2015
• Last Update Posted: Sep 12, 2019
• Last Verified: Aug 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Cancer; Rivaroxaban; Venous thromboembolism
• Additional relevant MeSH terms: Thromboembolism; Venous Thromboembolism; Rivaroxaban

Study Results

Participant Flow

Recruitment Details	A total of 841 participants were enrolled in the study to receive either of the 2 treatments: rivaroxaban or matching placebo.
Pre-assignment Detail	Deaths which were primary cause of treatment discontinuation (up to Day 180) are reported in participant flow excluding deaths which occurred after discontinuation.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Period Title: Overall Study
STARTED	421	420
Treated	404	405
COMPLETED	255	270
NOT COMPLETED	166	150

Baseline Characteristics

Arm/Group Title	Placebo	Rivaroxaban 10 mg	Total
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.	Total of all reporting groups
Overall Participants	421	420	841
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (11.19)	62.1 (11.22)	62 (11.2)
Sex: Female, Male (Count of Participants)
Female	215 51.1%	198 47.1%	413 49.1%
Male	206 48.9%	222 52.9%	428 50.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	69 16.4%	63 15%	132 15.7%
Not Hispanic or Latino	312 74.1%	314 74.8%	626 74.4%
Unknown or Not Reported	40 9.5%	43 10.2%	83 9.9%
Race/Ethnicity, Customized (Count of Participants) [Number]
White	346 82.2%	352 83.8%	698 83%
Black	18 4.3%	13 3.1%	31 3.7%
Asian	5 1.2%	6 1.4%	11 1.3%
Other	21 5%	10 2.4%	31 3.7%
Not reported	31 7.4%	39 9.3%	70 8.3%
Region of Enrollment (Count of Participants)
Belgium	3 0.7%	10 2.4%	13 1.5%
Brazil	55 13.1%	48 11.4%	103 12.2%
Bulgaria	15 3.6%	19 4.5%	34 4%
Canada	0 0%	3 0.7%	3 0.4%
Czech Republic	25 5.9%	12 2.9%	37 4.4%
France	29 6.9%	34 8.1%	63 7.5%
Germany	60 14.3%	53 12.6%	113 13.4%
Italy	17 4%	15 3.6%	32 3.8%
Russian Federation	59 14%	61 14.5%	120 14.3%
United Kingdom	30 7.1%	19 4.5%	49 5.8%
United States of America	128 30.4%	146 34.8%	274 32.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Time to First Occurrence of Primary Efficacy Endpoint (Composite and Components)
Description	Percentage of participants with time to the first occurrence of primary efficacy endpoint (composite and components) was reported. The primary efficacy composite endpoint is time to first occurrence of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, or VTE-related death as adjudicated by an independent blinded Clinical Endpoint Committee (CEC).
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Primary efficacy composite endpoint	8.79 2.1%	5.95 1.4%
Symptomatic lower extremity proximal DVT	1.90 0.5%	2.14 0.5%
Symptomatic lower extremity distal DVT	1.19 0.3%	0.48 0.1%
Symptomatic upper extremity DVT	1.43 0.3%	0.95 0.2%
Symptomatic non-fatal PE	1.19 0.3%	1.19 0.3%
Asymptomatic lower extremity proximal DVT	2.61 0.6%	0.95 0.2%
Incidental PE	2.38 0.6%	1.43 0.3%
VTE-related death	0.71 0.2%	0.24 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for primary efficacy composite endpoint.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.101
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.40 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for Symptomatic lower extremity proximal DVT.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.814
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.43 to 2.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for symptomatic lower extremity distal DVT.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.260
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.08 to 2.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for symptomatic upper extremity DVT.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.538
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.19 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for symptomatic non-fatal PE.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.977
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.29 to 3.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for asymptomatic lower extremity proximal DVT.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.063
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.11 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for incidental PE.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.301
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments	Statistical analysis for VTE-related death.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.314
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; 0.03 to 3.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Major Bleeding Events as Defined by International Society of Thrombosis and Haemostasis (ISTH)
Description	Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.
Time Frame	From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis population consisted of all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	404	405
Number [Percentage of participants]	0.99 0.2%	1.98 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rivaroxaban 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.265
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.96
	Confidence Interval	(2-Sided) 95%; 0.59 to 6.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Symptomatic VTE Events or VTE-Related Deaths
Description	Percentage of participants with time to first occurrence of the composite endpoint of symptomatic VTE events (symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, or symptomatic non-fatal PE) or VTE related deaths as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	5.23 1.2%	3.81 0.9%

4. Secondary Outcome

Title	Percentage of Participants With All-Cause Mortality
Description	Percentage of participants with all-cause mortality as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. Overall deaths occurred during observation period (defined by start to end date of the observation period [that is approximately 180 days] are reported here.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	23.8 5.7%	20.0 4.8%

5. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Fatal or Non-fatal Arterial Thromboembolic Events (ATE)
Description	Percentage of participants with time to first occurrence of fatal/non-fatal ATE (a composite of occurrence of myocardial infarction (MI), stroke [ischemic infarction with or without hemorrhagic conversion or primary hemorrhagic events - intraparenchymal hemorrhage, subdural hematoma or epidural hematoma] or any other ATE recorded) event as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	1.66 0.4%	0.95 0.2%

6. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Fatal or Non-fatal Visceral VTE
Description	Percentage of participants with time to the first occurrence of fatal or non-fatal visceral VTE as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	0.48 0.1%	0.24 0.1%

7. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Composite Efficacy Endpoint 1
Description	Percentage of participants with time to first occurrence of composite efficacy endpoint 1 (composite of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE or all-cause mortality) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	29.5 7%	23.1 5.5%

8. Secondary Outcome

Title	Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 2
Description	Percentage of participants with time to first occurrence of composite efficacy endpoint 2 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE or VTE-related deaths) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	5.23 1.2%	3.81 0.9%

9. Secondary Outcome

Title	Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 3
Description	Percentage of participants with time to first occurrence of composite efficacy endpoint 3 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, asymptomatic lower extremity proximal DVT, symptomatic non-fatal PE, incidental PE, VTE-related deaths, fatal/non-fatal ATE [MI, stroke {ischemic infarction with or without hemorrhagic conversion or primary hemorrhagic events - intraparenchymal hemorrhage, subdural hematoma or epidural hematoma} or any ATE] or fatal/non-fatal visceral VTE) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	10.7 2.5%	6.90 1.6%

10. Secondary Outcome

Title	Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 4
Description	Percentage of participants with time to first occurrence of composite efficacy endpoint 4 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, VTE-related deaths or major bleeding events up to Day 180) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported.
Time Frame	Up to Day 180

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	421	420
Number [Percentage of participants]	6.89 1.6%	5.71 1.4%

11. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Clinically Relevant Non-major Bleeding
Description	Percentage of participants with time to the first occurrence of clinically relevant non-major bleeding was reported. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, or unscheduled contact with a physician, or temporary cessation of study treatment, or discomfort such as pain, or impairment of activities of daily life.
Time Frame	From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis population consisted of all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	404	405
Number [Percentage of participants]	1.98 0.5%	2.72 0.6%

12. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Minor Bleeding
Description	Percentage of participants with time to the first occurrence of minor bleeding was reported. Minor bleeding (that is, minimal bleeding) is defined as overt bleeding episodes not meeting the criteria for major or clinically relevant non-major bleeding event.
Time Frame	From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis population consisted of all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	404	405
Number [Percentage of participants]	3.96 0.9%	6.91 1.6%

13. Secondary Outcome

Title	Percentage of Participants With Time to the First Occurrence of Any Bleeding
Description	Percentage of participants with time to the first occurrence of any bleeding event was reported. Any bleeding is defined as a composite of major bleeding, clinically relevant non-major bleeding, or minor bleeding.
Time Frame	From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis population consisted of all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.	Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
Measure Participants	404	405
Number [Percentage of participants]	6.44 1.5%	11.1 2.6%

Adverse Events

Time Frame	Up to 32 weeks
Adverse Event Reporting Description	The safety analysis population consisted of all randomized participants who received at least 1 dose of study drug. Deaths occurred throughout the study are reported below.
Arm/Group Title	Placebo		Rivaroxaban 10 mg
Arm/Group Description	Participants received placebo tablet matched to rivaroxaban orally once daily for 180 days.		Participants received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
All Cause Mortality
	Placebo		Rivaroxaban 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	106/404 (26.2%)		85/405 (21%)
Serious Adverse Events
	Placebo		Rivaroxaban 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/404 (31.7%)		134/405 (33.1%)
Blood and lymphatic system disorders
Anaemia	3/404 (0.7%)		3/405 (0.7%)
Febrile Neutropenia	4/404 (1%)		6/405 (1.5%)
Leukopenia	1/404 (0.2%)		0/405 (0%)
Neutropenia	3/404 (0.7%)		1/405 (0.2%)
Pancytopenia	1/404 (0.2%)		0/405 (0%)
Thrombocytopenia	2/404 (0.5%)		0/405 (0%)
Cardiac disorders
Atrial Fibrillation	2/404 (0.5%)		1/405 (0.2%)
Cardiotoxicity	0/404 (0%)		1/405 (0.2%)
Coronary Artery Disease	0/404 (0%)		1/405 (0.2%)
Pericardial Effusion	1/404 (0.2%)		0/405 (0%)
Supraventricular Tachycardia	0/404 (0%)		1/405 (0.2%)
Endocrine disorders
Inappropriate Antidiuretic Hormone Secretion	0/404 (0%)		1/405 (0.2%)
Gastrointestinal disorders
Abdominal Pain	3/404 (0.7%)		5/405 (1.2%)
Abdominal Pain Upper	1/404 (0.2%)		0/405 (0%)
Ascites	0/404 (0%)		1/405 (0.2%)
Constipation	0/404 (0%)		1/405 (0.2%)
Diarrhoea	2/404 (0.5%)		2/405 (0.5%)
Duodenal Obstruction	0/404 (0%)		3/405 (0.7%)
Dyspepsia	0/404 (0%)		1/405 (0.2%)
Dysphagia	4/404 (1%)		1/405 (0.2%)
Enterocolitis	0/404 (0%)		1/405 (0.2%)
Faecaloma	0/404 (0%)		1/405 (0.2%)
Gastrointestinal Disorder	0/404 (0%)		1/405 (0.2%)
Gastrointestinal Obstruction	1/404 (0.2%)		0/405 (0%)
Gastrointestinal Perforation	1/404 (0.2%)		0/405 (0%)
Gastrointestinal Toxicity	0/404 (0%)		1/405 (0.2%)
Intestinal Infarction	0/404 (0%)		1/405 (0.2%)
Intestinal Ischaemia	0/404 (0%)		1/405 (0.2%)
Intestinal Obstruction	0/404 (0%)		1/405 (0.2%)
Nausea	2/404 (0.5%)		1/405 (0.2%)
Small Intestinal Obstruction	3/404 (0.7%)		3/405 (0.7%)
Vomiting	3/404 (0.7%)		2/405 (0.5%)
General disorders
Chest Pain	1/404 (0.2%)		0/405 (0%)
Condition Aggravated	0/404 (0%)		1/405 (0.2%)
Death	2/404 (0.5%)		0/405 (0%)
Disease Progression	2/404 (0.5%)		0/405 (0%)
Fatigue	0/404 (0%)		1/405 (0.2%)
General Physical Health Deterioration	4/404 (1%)		5/405 (1.2%)
Generalised Oedema	1/404 (0.2%)		0/405 (0%)
Malaise	0/404 (0%)		2/405 (0.5%)
Mucosal Inflammation	1/404 (0.2%)		0/405 (0%)
Multiple Organ Dysfunction Syndrome	1/404 (0.2%)		0/405 (0%)
Non-Cardiac Chest Pain	1/404 (0.2%)		0/405 (0%)
Pyrexia	8/404 (2%)		8/405 (2%)
Hepatobiliary disorders
Bile Duct Obstruction	3/404 (0.7%)		1/405 (0.2%)
Cholangitis	1/404 (0.2%)		2/405 (0.5%)
Cholecystitis	1/404 (0.2%)		0/405 (0%)
Cholestasis	1/404 (0.2%)		1/405 (0.2%)
Hypertransaminasaemia	0/404 (0%)		1/405 (0.2%)
Jaundice	0/404 (0%)		1/405 (0.2%)
Immune system disorders
Drug Hypersensitivity	0/404 (0%)		1/405 (0.2%)
Infections and infestations
Abdominal Sepsis	1/404 (0.2%)		0/405 (0%)
Abscess Limb	0/404 (0%)		1/405 (0.2%)
Anal Abscess	0/404 (0%)		1/405 (0.2%)
Appendicitis	0/404 (0%)		1/405 (0.2%)
Atypical Pneumonia	2/404 (0.5%)		1/405 (0.2%)
Bacteraemia	1/404 (0.2%)		0/405 (0%)
Biliary Sepsis	2/404 (0.5%)		0/405 (0%)
Cellulitis	1/404 (0.2%)		3/405 (0.7%)
Cholecystitis Infective	1/404 (0.2%)		0/405 (0%)
Clostridium Difficile Colitis	1/404 (0.2%)		0/405 (0%)
Device Related Infection	0/404 (0%)		1/405 (0.2%)
Diverticulitis	2/404 (0.5%)		1/405 (0.2%)
Febrile Infection	1/404 (0.2%)		0/405 (0%)
Gastroenteritis Viral	1/404 (0.2%)		0/405 (0%)
Klebsiella Sepsis	1/404 (0.2%)		0/405 (0%)
Lower Respiratory Tract Infection	3/404 (0.7%)		0/405 (0%)
Lung Infection	1/404 (0.2%)		2/405 (0.5%)
Neutropenic Sepsis	3/404 (0.7%)		0/405 (0%)
Oral Candidiasis	0/404 (0%)		1/405 (0.2%)
Pneumonia	4/404 (1%)		10/405 (2.5%)
Pneumonia Bacterial	1/404 (0.2%)		0/405 (0%)
Respiratory Tract Infection	1/404 (0.2%)		0/405 (0%)
Sepsis	4/404 (1%)		6/405 (1.5%)
Septic Shock	1/404 (0.2%)		1/405 (0.2%)
Sinusitis	1/404 (0.2%)		0/405 (0%)
Tracheobronchitis	1/404 (0.2%)		0/405 (0%)
Urinary Tract Infection	2/404 (0.5%)		3/405 (0.7%)
Injury, poisoning and procedural complications
Hip Fracture	2/404 (0.5%)		0/405 (0%)
Pubis Fracture	0/404 (0%)		1/405 (0.2%)
Investigations
Aspiration Bronchial	0/404 (0%)		1/405 (0.2%)
Blood Bilirubin Increased	0/404 (0%)		2/405 (0.5%)
General Physical Condition Abnormal	0/404 (0%)		1/405 (0.2%)
Glomerular Filtration Rate Decreased	0/404 (0%)		1/405 (0.2%)
Platelet Count Decreased	1/404 (0.2%)		0/405 (0%)
Metabolism and nutrition disorders
Decreased Appetite	1/404 (0.2%)		0/405 (0%)
Dehydration	5/404 (1.2%)		3/405 (0.7%)
Diabetic Ketoacidosis	0/404 (0%)		1/405 (0.2%)
Electrolyte Imbalance	1/404 (0.2%)		0/405 (0%)
Failure to Thrive	0/404 (0%)		1/405 (0.2%)
Feeding Intolerance	1/404 (0.2%)		0/405 (0%)
Hypercalcaemia	0/404 (0%)		1/405 (0.2%)
Hyperglycaemia	0/404 (0%)		2/405 (0.5%)
Hypokalaemia	1/404 (0.2%)		1/405 (0.2%)
Hyponatraemia	0/404 (0%)		1/405 (0.2%)
Musculoskeletal and connective tissue disorders
Back Pain	1/404 (0.2%)		2/405 (0.5%)
Bursitis	1/404 (0.2%)		0/405 (0%)
Muscle Tightness	1/404 (0.2%)		0/405 (0%)
Muscular Weakness	1/404 (0.2%)		2/405 (0.5%)
Musculoskeletal Pain	1/404 (0.2%)		0/405 (0%)
Pathological Fracture	1/404 (0.2%)		0/405 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	1/404 (0.2%)		0/405 (0%)
Lung Adenocarcinoma	1/404 (0.2%)		0/405 (0%)
Malignant Neoplasm Progression	33/404 (8.2%)		29/405 (7.2%)
Metastases to Central Nervous System	1/404 (0.2%)		0/405 (0%)
Metastases to Liver	0/404 (0%)		2/405 (0.5%)
Metastases to Lymph Nodes	1/404 (0.2%)		0/405 (0%)
Neoplasm Progression	0/404 (0%)		1/405 (0.2%)
Ovarian Cancer	1/404 (0.2%)		0/405 (0%)
Tumour Associated Fever	1/404 (0.2%)		0/405 (0%)
Nervous system disorders
Headache	1/404 (0.2%)		0/405 (0%)
Lethargy	0/404 (0%)		1/405 (0.2%)
Muscle Contractions Involuntary	1/404 (0.2%)		0/405 (0%)
Paraesthesia	1/404 (0.2%)		0/405 (0%)
Syncope	1/404 (0.2%)		1/405 (0.2%)
Transient Global Amnesia	0/404 (0%)		1/405 (0.2%)
Psychiatric disorders
Confusional State	0/404 (0%)		1/405 (0.2%)
Renal and urinary disorders
Acute Kidney Injury	0/404 (0%)		3/405 (0.7%)
Dysuria	0/404 (0%)		1/405 (0.2%)
Hydronephrosis	0/404 (0%)		1/405 (0.2%)
Renal Failure	0/404 (0%)		1/405 (0.2%)
Reproductive system and breast disorders
Female Genital Tract Fistula	0/404 (0%)		1/405 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/404 (0.2%)		0/405 (0%)
Chronic Obstructive Pulmonary Disease	0/404 (0%)		1/405 (0.2%)
Dyspnoea	5/404 (1.2%)		3/405 (0.7%)
Laryngospasm	1/404 (0.2%)		0/405 (0%)
Pleural Effusion	3/404 (0.7%)		3/405 (0.7%)
Pneumonitis	0/404 (0%)		1/405 (0.2%)
Pneumothorax	0/404 (0%)		1/405 (0.2%)
Respiratory Distress	1/404 (0.2%)		0/405 (0%)
Respiratory Failure	2/404 (0.5%)		0/405 (0%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	1/404 (0.2%)		0/405 (0%)
Drug Eruption	1/404 (0.2%)		0/405 (0%)
Rash	1/404 (0.2%)		0/405 (0%)
Rash Macular	1/404 (0.2%)		0/405 (0%)
Vascular disorders
Superior Vena Cava Syndrome	1/404 (0.2%)		0/405 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Rivaroxaban 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/404 (35.9%)		138/405 (34.1%)
Blood and lymphatic system disorders
Anaemia	59/404 (14.6%)		46/405 (11.4%)
Neutropenia	24/404 (5.9%)		25/405 (6.2%)
Gastrointestinal disorders
Constipation	12/404 (3%)		29/405 (7.2%)
Diarrhoea	36/404 (8.9%)		34/405 (8.4%)
Nausea	55/404 (13.6%)		55/405 (13.6%)
Vomiting	17/404 (4.2%)		28/405 (6.9%)
General disorders
Fatigue	32/404 (7.9%)		44/405 (10.9%)
Metabolism and nutrition disorders
Decreased Appetite	25/404 (6.2%)		21/405 (5.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.