A Phase 2 Pilot Study of Apixaban for the Prevention of Thromboembolic Events in Patients With Advanced (Metastatic) Cancer

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00320255
• Collaborator: Ontario Clinical Oncology Group (OCOG) (Other)
• Enrollment: 130
• Locations: 14
• Arms: 6
• Duration (Months): 31
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to learn whether apixaban is well-tolerated and acceptable as anticoagulant therapy, when administered to patients with advanced or metastatic cancer and at increased risk for venous thromboembolic events. Demonstration of a favorable benefit:risk profile could lead to significant reduction in this serious and sometimes fatal complication of ongoing cancer and its treatment.

Condition or Disease	Intervention/Treatment	Phase
Thrombosis; Cancer; Pulmonary Embolism	Drug: Apixaban; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind, Placebo-controlled Study of Apixaban for the Prevention of Thromboembolic Events in Patients Undergoing Treatment for Advanced Cancer: A Phase 2 Pilot Study
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Cohort 1: Placebo Participants received placebo tablets once daily	Drug: Placebo; Oral tablets administered once daily
Placebo Comparator: Cohort 1: Apixaban, 5 mg Participants received apixaban as tablet, 5 mg, once daily	Drug: Apixaban; Oral tablets administered once daily in 5-, 10-, or 20-mg dose; Other Names: BMS-562247
Active Comparator: Cohort 1: Apixaban, 10 mg Participants received apixaban as tablet, 10 mg, once daily	Drug: Apixaban; Oral tablets administered once daily in 5-, 10-, or 20-mg dose; Other Names: BMS-562247
Active Comparator: Cohort 1: Apixaban, 20 mg Participants received apixaban as tablet, 20 mg, once daily	Drug: Apixaban; Oral tablets administered once daily in 5-, 10-, or 20-mg dose; Other Names: BMS-562247
Placebo Comparator: Cohort 2: Placebo Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Drug: Placebo; Oral tablets administered once daily
Active Comparator: Cohort 2: Apixaban, 5 mg Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.	Drug: Apixaban; Oral tablets administered once daily in 5-, 10-, or 20-mg dose; Other Names: BMS-562247

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding [From first dose to 2 days following last dose of study drug]

   Major bleeding was defined as clinically overt bleeding accompanied by 1 or more of the following: A decrease in hemoglobin of 20 g/L or more or Required transfusion of 2 or more units of packed red blood cells or whole blood, or Occurred in a critical site Contributed to death. CRNM bleeding was defined as bleeding that did not meet the criteria for major bleeding but that, in routine clinical practice, would be considered relevant and not trivial by a patient and physician. Such bleeding satisfied a priori criteria defined by the ICAC, including: Skin hematoma Epistaxis that lasted for longer than 5 minutes, was repetitive, or led to an intervention Hematuria that was macroscopic and either spontaneous or lasted for longer than 24 hours after instrumentation of the urogenital tract Any other bleeding type that was considered to have clinical consequences.

Secondary Outcome Measures

1. Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death [First dose to 2 days following last dose of study drug]

   VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

2. Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death [First dose to 30 days following last dose of study drug]

   Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments (popliteal vein or higher) of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan (nonhigh probability) with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

3. Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death [First dose to 2 days following last dose of study drug]

   VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

4. Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death [First dose to 2 days following last dose of study drug]

   VTE includes symptomatic DVT and PE. Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

5. Number of Participants With All-Cause Death [First dose to 2 days following last dose of study drug]

6. Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) [First dose to 2 days following last dose of study drug]

   Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels of greater than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

7. Number of Participants With Nonfatal Pulmonary Embolism [First dose to 2 days following last dose of study drug]

   Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

8. Number of Participants With Deep Vein Thrombosis [First dose to 2 days following last dose of study drug]

   Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

9. Number of Participants With Distal Deep Vein Thrombosis [First dose to 2 days following last dose of study drug]

   Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

10. Number of Participants With Proximal Deep Vein Thrombosis [First dose to 2 days following last dose of study drug]

    Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

11. Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs [First dose to 2 days following last dose of study drug]

    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Recipients of either first- or second-line chemotherapy for advanced or metastatic lung, breast, gastrointestinal, bladder, ovarian, or prostate cancer or myeloma, selected lymphomas, or cancer of unknown origin

• Able to begin study medication ≤6 weeks of starting either first- or second-line chemotherapy.

• Expected course of chemotherapy must have been ≥ 90 days after the start of chemotherapy

• Per Protocol Amendment 5, patients receiving bevacizumab were eligible to participate, provided that bevacizumab was used for indications approved by local country law

Key Exclusion Criteria:

• Women who are pregnant, breastfeeding

• History of deep vein thrombosis or pulmonary embolism

• Active bleeding or at high risk of bleeding

• Metastatic brain cancer

• Familial bleeding diathesis

• Serious hemorrhage requiring hospitalization, transfusion, or surgical intervention within 4 weeks of study entry

• Expected survival <6 months or an Eastern Cooperative Oncology Group performance status ≥3.

• Candidates for bone marrow transplantation within the 12-week treatment period or 30-day follow-up period

• Uncontrolled hypertension (systolic blood pressure >200 mm Hg and/or diastolic blood pressure >110 mm Hg

• Coagulopathy (international normalized ratio >1.5 or platelet count <10010^9/L) if not yet receiving chemotherapy or <5010^{9/L if receiving chemotherapy). Platelet count must have been >100*10}9/L before starting study medication

• One or more of the following: alanine aminotransferase >3 times the upper limit of normal (ULN), total bilirubin >2*ULN, or calculated creatinine clearance <30 mL/min.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85724
2	Univ. Of Southern Calif. /Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	Dana-Farber Cancer Inst	Boston	Massachusetts	United States	02115
4	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
5	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
6	Mount Sinai School Of Medicine	New York	New York	United States	10029
7	University Of Rochester	Rochester	New York	United States	14642
8	University Of Texas Md Anderson Cancer Ctr	Houston	Texas	United States	77030
9	Local Institution	Hamilton	Ontario	Canada	L8V 2C5
10	Local Institution	London	Ontario	Canada	N6A 4L6
11	Local Institution	Toronto	Ontario	Canada	M4N 3M5
12	Local Institution	Toronto	Ontario	Canada	M5G 2M9
13	Local Institution	Montreal	Quebec	Canada	H1T 2M4
14	Local Institution	Montreal	Quebec	Canada	H3G 1A4

Sponsors and Collaborators

• Bristol-Myers Squibb
• Ontario Clinical Oncology Group (OCOG)

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00320255
• Other Study ID Numbers: CV185-027
• First Posted: May 3, 2006
• Last Update Posted: Aug 16, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Bristol-Myers Squibb: anticoagulant
• Additional relevant MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Apixaban

Study Results

Participant Flow

Pre-assignment Detail	A total of 130 participants were enrolled and randomized; however, 1 withdrew consent and 2 no longer met study criteria. Therefore, 127 participants were treated. Reasons Not Completed listed in the data table below were summarized for 127 participants who received treatment.

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Period Title: Overall Study
STARTED	30	32	30	33	2	3
Received Treatment	29	32	29	32	2	3
COMPLETED	19	25	24	25	2	3
NOT COMPLETED	11	7	6	8	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg	Total
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.	Total of all reporting groups
Overall Participants	30	32	30	33	2	3	130
Age, Customized (Number) [Number]
Younger than 65 years	17 56.7%	28 87.5%	19 63.3%	17 51.5%	1 50%	3 100%	85 65.4%
65 years and older but younger than 75 years	8 26.7%	4 12.5%	9 30%	8 24.2%	1 50%	0 0%	30 23.1%
75 years and older	5 16.7%	0 0%	2 6.7%	8 24.2%	0 0%	0 0%	15 11.5%
Sex: Female, Male (Count of Participants)
Female	15 50%	17 53.1%	17 56.7%	13 39.4%	0 0%	2 66.7%	64 49.2%
Male	15 50%	15 46.9%	13 43.3%	20 60.6%	2 100%	1 33.3%	66 50.8%
Race/Ethnicity, Customized (Number) [Number]
White	27 90%	27 84.4%	26 86.7%	25 75.8%	2 100%	3 100%	110 84.6%
Black/African American	0 0%	2 6.3%	1 3.3%	3 9.1%	0 0%	0 0%	6 4.6%
Asian	2 6.7%	2 6.3%	1 3.3%	2 6.1%	0 0%	0 0%	7 5.4%
Native Hawaiian or other Pacific Islander	0 0%	1 3.1%	0 0%	0 0%	0 0%	0 0%	1 0.8%
Other	1 3.3%	0 0%	2 6.7%	3 9.1%	0 0%	0 0%	6 4.6%

Outcome Measures

1. Secondary Outcome

Title	Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death
Description	VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	4 13.3%	0 0%	0 0%	1 3%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death
Description	Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments (popliteal vein or higher) of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan (nonhigh probability) with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time Frame	First dose to 30 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	3 10%	0 0%	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death
Description	VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	4 13.3%	0 0%	0 0%	1 3%	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death
Description	VTE includes symptomatic DVT and PE. Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	3 10%	0 0%	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With All-Cause Death
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With Pulmonary Embolism (Fatal or Nonfatal)
Description	Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels of greater than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixiban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	1 3.3%	0 0%	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Nonfatal Pulmonary Embolism
Description	Any 1 of the following was considered diagnostic for PE: Constant intraluminal filling defects in 2 or more views on pulmonary angiography Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	1 3.3%	0 0%	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With Deep Vein Thrombosis
Description	Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	4 13.3%	0 0%	0 0%	1 3%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Distal Deep Vein Thrombosis
Description	Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	1 3.3%	0 0%	0 0%	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Proximal Deep Vein Thrombosis
Description	Any 1 of the following was considered diagnostic for DVT: New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	3 10%	0 0%	0 0%	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame	First dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Deaths	2 6.7%	1 3.1%	0 0%	0 0%	0 0%	0 0%
SAEs	9 30%	6 18.8%	3 10%	5 15.2%	1 50%	0 0%
Bleeding AEs	6 20%	15 46.9%	11 36.7%	12 36.4%	1 50%	2 66.7%
Discontinuations due to AEs	7 23.3%	4 12.5%	4 13.3%	4 12.1%	1 50%	0 0%

12. Primary Outcome

Title	Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding
Description	Major bleeding was defined as clinically overt bleeding accompanied by 1 or more of the following: A decrease in hemoglobin of 20 g/L or more or Required transfusion of 2 or more units of packed red blood cells or whole blood, or Occurred in a critical site Contributed to death. CRNM bleeding was defined as bleeding that did not meet the criteria for major bleeding but that, in routine clinical practice, would be considered relevant and not trivial by a patient and physician. Such bleeding satisfied a priori criteria defined by the ICAC, including: Skin hematoma Epistaxis that lasted for longer than 5 minutes, was repetitive, or led to an intervention Hematuria that was macroscopic and either spontaneous or lasted for longer than 24 hours after instrumentation of the urogenital tract Any other bleeding type that was considered to have clinical consequences.
Time Frame	From first dose to 2 days following last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Cohort 1: Placebo	Cohort 1: Apixaban, 5 mg	Cohort 1: Apixaban, 10 mg	Cohort 1: Apixaban, 20 mg	Cohort 2: Placebo	Cohort 2: Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily	Participants received apixaban as tablet, 5 mg, once daily	Participants received apixaban as tablet, 10 mg, once daily	Participants received apixaban as tablet, 20 mg, once daily	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.	Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Measure Participants	29	32	29	32	2	3
Number (95% Confidence Interval) [Participants]	1 3.3%	1 3.1%	1 3.3%	4 12.1%	2 100%	3 100%

Adverse Events

Arm/Group Title	Cohort 1: Placebo		Cohort 1: Apixaban, 5 mg		Cohort 1: Apixaban, 10 mg		Cohort 1: Apixaban, 20 mg		Cohort 2: Placebo		Cohort : Apixaban, 5 mg
Arm/Group Description	Participants received placebo tablets once daily		Participants received apixaban as tablet, 5 mg, once daily		Participants received apixaban as tablet, 10 mg, once daily		Participants received apixaban as tablet, 20 mg, once daily		Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.		:Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
All Cause Mortality
	Cohort 1: Placebo		Cohort 1: Apixaban, 5 mg		Cohort 1: Apixaban, 10 mg		Cohort 1: Apixaban, 20 mg		Cohort 2: Placebo		Cohort : Apixaban, 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1: Placebo		Cohort 1: Apixaban, 5 mg		Cohort 1: Apixaban, 10 mg		Cohort 1: Apixaban, 20 mg		Cohort 2: Placebo		Cohort : Apixaban, 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/29 (31%)		6/32 (18.8%)		3/29 (10.3%)		5/32 (15.6%)		1/2 (50%)		0/3 (0%)
Blood and lymphatic system disorders
Febrile neutropenia	2/29 (6.9%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Pancytopenia	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Anaemia	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Cardiac disorders
Cardiac failure congestive	1/29 (3.4%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Constipation	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Duodenal ulcer	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Nausea	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Lower gastrointestinal tract hemorrhage	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Rectal haemorrhage	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Peptic ulcer perforation	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Diarrhoea	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Vomiting	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
General disorders
Death	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Disease progression	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Hepatobiliary disorders
Cholecystitis	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Infections and infestations
Pneumonia	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Herpes zoster	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Sepsis	0/29 (0%)		0/32 (0%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Bacterial infection	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Viral infection	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Bacteraemia	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Infection	3/29 (10.3%)		1/32 (3.1%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Investigations
Liver function test abnormal	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Dehydration	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Hyperglycaemia	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Back pain	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Renal and urinary disorders
Renal failure	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Renal failure acute	0/29 (0%)		0/32 (0%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/29 (6.9%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Pleuritic pain	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Dyspnoea	0/29 (0%)		1/32 (3.1%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Surgical and medical procedures
Hip arthroplasty	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Spinal decompression	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Vascular disorders
Deep vein thrombosis	1/29 (3.4%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: Placebo		Cohort 1: Apixaban, 5 mg		Cohort 1: Apixaban, 10 mg		Cohort 1: Apixaban, 20 mg		Cohort 2: Placebo		Cohort : Apixaban, 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/29 (82.8%)		28/32 (87.5%)		24/29 (82.8%)		30/32 (93.8%)		2/2 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Neutropenia	0/29 (0%)		3/32 (9.4%)		0/29 (0%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Cardiac disorders
Tachycardia	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Ear and labyrinth disorders
Deafness	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Eye disorders
Visual impairment	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Vision blurred	0/29 (0%)		2/32 (6.3%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Gastrointestinal disorders
Dry mouth	2/29 (6.9%)		3/32 (9.4%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Abdominal pain	1/29 (3.4%)		2/32 (6.3%)		0/29 (0%)		0/32 (0%)		1/2 (50%)		1/3 (33.3%)
Abdominal pain upper	0/29 (0%)		0/32 (0%)		0/29 (0%)		2/32 (6.3%)		0/2 (0%)		1/3 (33.3%)
Anal haemorrhage	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Constipation	5/29 (17.2%)		5/32 (15.6%)		2/29 (6.9%)		5/32 (15.6%)		1/2 (50%)		1/3 (33.3%)
Mouth haemorrhage	0/29 (0%)		0/32 (0%)		0/29 (0%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Nausea	1/29 (3.4%)		3/32 (9.4%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Proctalgia	0/29 (0%)		2/32 (6.3%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Ascites	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Flatulence	0/29 (0%)		0/32 (0%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Abdominal distension	0/29 (0%)		1/32 (3.1%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		1/3 (33.3%)
Diarrhoea	4/29 (13.8%)		5/32 (15.6%)		7/29 (24.1%)		10/32 (31.3%)		2/2 (100%)		1/3 (33.3%)
Dyspepsia	1/29 (3.4%)		3/32 (9.4%)		1/29 (3.4%)		2/32 (6.3%)		1/2 (50%)		0/3 (0%)
Gingival bleeding	0/29 (0%)		0/32 (0%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		1/3 (33.3%)
General disorders
Chest pain	0/29 (0%)		1/32 (3.1%)		2/29 (6.9%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Fatigue	2/29 (6.9%)		2/32 (6.3%)		1/29 (3.4%)		7/32 (21.9%)		0/2 (0%)		0/3 (0%)
Chills	0/29 (0%)		0/32 (0%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		1/3 (33.3%)
Pyrexia	2/29 (6.9%)		4/32 (12.5%)		2/29 (6.9%)		3/32 (9.4%)		0/2 (0%)		1/3 (33.3%)
Early satiety	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Oedema peripheral	3/29 (10.3%)		2/32 (6.3%)		2/29 (6.9%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Asthenia	2/29 (6.9%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Gait disturbance	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Mucosal inflammation	0/29 (0%)		2/32 (6.3%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Pain	1/29 (3.4%)		0/32 (0%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Chest discomfort	0/29 (0%)		2/32 (6.3%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Infections and infestations
Pneumonia	2/29 (6.9%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Urinary tract infection	0/29 (0%)		0/32 (0%)		2/29 (6.9%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Pilonidal cyst	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Rectal abscess	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Sinusitis	2/29 (6.9%)		1/32 (3.1%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Upper respiratory tract infection	1/29 (3.4%)		0/32 (0%)		3/29 (10.3%)		4/32 (12.5%)		1/2 (50%)		0/3 (0%)
Injury, poisoning and procedural complications
Contusion	0/29 (0%)		1/32 (3.1%)		3/29 (10.3%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Investigations
Blood glucose increased	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		1/3 (33.3%)
Haemoglobin decreased	0/29 (0%)		0/32 (0%)		0/29 (0%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Weight increased	0/29 (0%)		2/32 (6.3%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Alanine aminotransferase increased	0/29 (0%)		1/32 (3.1%)		2/29 (6.9%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Blood magnesium decreased	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Blood potassium decreased	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Weight decreased	2/29 (6.9%)		2/32 (6.3%)		2/29 (6.9%)		2/32 (6.3%)		0/2 (0%)		1/3 (33.3%)
White blood cell count decreased	1/29 (3.4%)		1/32 (3.1%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Anorexia	2/29 (6.9%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Hyponatraemia	0/29 (0%)		0/32 (0%)		2/29 (6.9%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	2/29 (6.9%)		3/32 (9.4%)		5/29 (17.2%)		4/32 (12.5%)		1/2 (50%)		1/3 (33.3%)
Musculoskeletal pain	2/29 (6.9%)		2/32 (6.3%)		3/29 (10.3%)		3/32 (9.4%)		0/2 (0%)		0/3 (0%)
Arthralgia	1/29 (3.4%)		4/32 (12.5%)		3/29 (10.3%)		1/32 (3.1%)		0/2 (0%)		1/3 (33.3%)
Neck pain	1/29 (3.4%)		2/32 (6.3%)		2/29 (6.9%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Muscle spasms	1/29 (3.4%)		0/32 (0%)		2/29 (6.9%)		2/32 (6.3%)		1/2 (50%)		0/3 (0%)
Musculoskeletal chest pain	1/29 (3.4%)		0/32 (0%)		2/29 (6.9%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Back pain	2/29 (6.9%)		1/32 (3.1%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Myalgia	2/29 (6.9%)		2/32 (6.3%)		3/29 (10.3%)		1/32 (3.1%)		0/2 (0%)		1/3 (33.3%)
Nervous system disorders
Neuropathy peripheral	1/29 (3.4%)		0/32 (0%)		3/29 (10.3%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Paraesthesia	5/29 (17.2%)		1/32 (3.1%)		2/29 (6.9%)		3/32 (9.4%)		0/2 (0%)		1/3 (33.3%)
Dysgeusia	1/29 (3.4%)		2/32 (6.3%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Dizziness	1/29 (3.4%)		3/32 (9.4%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Headache	3/29 (10.3%)		1/32 (3.1%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Hypoaesthesia	2/29 (6.9%)		3/32 (9.4%)		2/29 (6.9%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Peripheral sensory neuropathy	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		1/2 (50%)		0/3 (0%)
Psychiatric disorders
Anxiety	1/29 (3.4%)		3/32 (9.4%)		0/29 (0%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)
Nervousness	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Depression	1/29 (3.4%)		1/32 (3.1%)		1/29 (3.4%)		1/32 (3.1%)		1/2 (50%)		1/3 (33.3%)
Insomnia	3/29 (10.3%)		2/32 (6.3%)		1/29 (3.4%)		2/32 (6.3%)		2/2 (100%)		1/3 (33.3%)
Renal and urinary disorders
Dysuria	0/29 (0%)		0/32 (0%)		2/29 (6.9%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Pollakiuria	2/29 (6.9%)		1/32 (3.1%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/29 (3.4%)		2/32 (6.3%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Epistaxis	4/29 (13.8%)		8/32 (25%)		4/29 (13.8%)		7/32 (21.9%)		1/2 (50%)		2/3 (66.7%)
Cough	2/29 (6.9%)		1/32 (3.1%)		2/29 (6.9%)		1/32 (3.1%)		1/2 (50%)		1/3 (33.3%)
Dyspnoea	4/29 (13.8%)		3/32 (9.4%)		2/29 (6.9%)		3/32 (9.4%)		0/2 (0%)		0/3 (0%)
Nasal dryness	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Atelectasis	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Dysphonia	0/29 (0%)		0/32 (0%)		0/29 (0%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Dry skin	1/29 (3.4%)		1/32 (3.1%)		0/29 (0%)		4/32 (12.5%)		0/2 (0%)		0/3 (0%)
Skin hyperpigmentation	0/29 (0%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		1/3 (33.3%)
Alopecia	0/29 (0%)		4/32 (12.5%)		6/29 (20.7%)		7/32 (21.9%)		0/2 (0%)		0/3 (0%)
Skin discolouration	0/29 (0%)		0/32 (0%)		0/29 (0%)		1/32 (3.1%)		1/2 (50%)		0/3 (0%)
Acne	2/29 (6.9%)		1/32 (3.1%)		0/29 (0%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Palmar-plantar erythrodysaesthesia syndrome	0/29 (0%)		3/32 (9.4%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Rash	1/29 (3.4%)		3/32 (9.4%)		5/29 (17.2%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Erythema	0/29 (0%)		2/32 (6.3%)		1/29 (3.4%)		2/32 (6.3%)		0/2 (0%)		0/3 (0%)
Night sweats	0/29 (0%)		2/32 (6.3%)		1/29 (3.4%)		0/32 (0%)		1/2 (50%)		0/3 (0%)
Vascular disorders
Haemorrhage	0/29 (0%)		3/32 (9.4%)		1/29 (3.4%)		0/32 (0%)		0/2 (0%)		0/3 (0%)
Deep vein thrombosis	2/29 (6.9%)		0/32 (0%)		1/29 (3.4%)		1/32 (3.1%)		0/2 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.