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Safety Study of Apixaban in Recent Acute Coronary Syndrome

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00313300
Collaborator
(none)
1,741
Enrollment
151
Locations
4
Arms
24
Duration (Months)
11.5
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to determine whether apixaban will be safe in people who have recently had unstable angina or a heart attack.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
1741 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
A Phase 2, Placebo-Controlled, Randomized, Double Blind, Parallel Arm, Dose Ranging Study to Evaluate Safety and Efficacy of Apixaban in Patients With a Recent Acute Coronary Syndrome.
Study Start Date :
May 1, 2006
Actual Primary Completion Date :
May 1, 2008
Actual Study Completion Date :
May 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: A1

Drug: Apixaban
Tablets, Oral, 2.5 mg, twice daily, 26 weeks
Experimental: A2

Drug: Apixaban
Tablets, Oral, 10 mg, once daily, 26 weeks
Placebo Comparator: A3

Drug: Placebo
Tablets, Oral, 0, twice daily, 26 weeks
Experimental: A4

Drug: Apixaban
Tablets, Oral 10 mg, twice daily, 26 weeks

Outcome Measures

Primary Outcome Measures

  1. Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses [From first dose of study drug (Day 1) to last dose plus 2 days, up to Year 2 of the Study]

    Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The primary outcome is based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B. The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups (10mg BID, 20mg QD) and the resulting lower duration of exposure for these groups.

Secondary Outcome Measures

  1. Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants [Randomization to 182 days after randomization (183 days)]

    Events were adjudicated by the Clinical Events Committee (CEC). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B.

  2. Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses [first dose (Day 1) to last dose plus 2 days (or for SAEs, plus 30 days), up to Year 2 of the Study]

    Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events includes major bleeding, clinically relevant non-major bleeding and minor bleeding. Treatment Period refers to the period from first dose through 2 days, or through 30 days for Serious Adverse Event (SAE) tabulations, after discontinuation of study drug. Data in this outcome are combined across Phase A and Phase B.

  3. Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants [Day of randomization to 182 days after day of randomization (183 days)]

    Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B

  4. Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses [from first dose (Day 1) to last dose plus 2 days, up to Year 2 of the Study]

    Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the Clinical Events Committee. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%).

  5. Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B [Day of randomization and ends on high dose termination date, 1-Oct-2007]

    Phase B Adjusted Intended Treatment Period=day of randomization and ends on termination date of high dose apixaban, 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.

  6. Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B [From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007]

    Bleeding was assessed using ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups and the lower duration of exposure. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).

  7. Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B [From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007]

    Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events included major bleeding, clinically relevant non-major bleeding and minor bleeding. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).

  8. Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B [Day of randomization up to high dose termination, 1-Oct-2007]

    Phase B Adjusted Intended Treatment Period=day of randomization and ends on 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.

  9. Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B [From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007]

    Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:

  • Recent (< = 7 days) Acute Coronary Syndrome (ACS).

  • Clinically stable on optimal treatment

Key Exclusion Criteria:

  • High bleeding risk.

  • Ongoing anticoagulant use.

  • Need for chronic (>3 months) daily nonsteroidal anti-inflammatory drug (NSAID) or chronic high dose acetylsalicylic acid (ASA) use (>325 mg/day

Contacts and Locations

Locations

Site City State Country Postal Code
1 Scottsdale Cardiovasular Research Institute Scottsdale Arizona United States 85251
2 Los Angeles County & University Of Southern Ca. Medical Cen. Los Angeles California United States 90033
3 Radiant Research,Santa Rosa Santa Rosa California United States 95405
4 South Denver Cardiology Associates Littleton Colorado United States 80120
5 Watson Clinic Center For Research Lakeland Florida United States 33805
6 Heart & Vasc Inst Of Fl Safety Harbor Florida United States 34695
7 Indian River Medical Center Vero Beach Florida United States 32960
8 Cardiac Disease Specialists, P.C. Atlanta Georgia United States 30309
9 Georgia Heart Specialists Covington Georgia United States 30014
10 Heartcare Midwest Peoria Illinois United States 61614
11 The Care Group, Llc. Indianapolis Indiana United States 46290
12 Iowa Heart Center Des Moines Iowa United States 50314
13 University Of Kentucky Lexington Kentucky United States 40536
14 William Beaumont Hospital-Troy Troy Michigan United States 48085
15 New York Cardiovascular Associates New York New York United States 10001
16 Unc Hospitals, Department Of Medicine Chapel Hill North Carolina United States 27599
17 Dumc Durham North Carolina United States 27705
18 Carolina Heart Specialists Gastonia North Carolina United States 28054
19 Piedmont Cardiology Associates Hickory North Carolina United States 28602
20 Wake Forest Univ Health Sciences Winston-Salem North Carolina United States 27157
21 Midwest Cardiology Research Foundation Columbus Ohio United States 43214
22 The Dayton Heart Center Dayton Ohio United States 45414
23 Oklahoma Cardiovascular Research Group Oklahoma City Oklahoma United States 73120
24 Geisinger Clinic - Cardiology Danville Pennsylvania United States 17822
25 Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
26 Rhode Island Hospital Providence Rhode Island United States 02903
27 Cardiovascular Associates, P.C Kingsport Tennessee United States 37660
28 University Of Texas Medical School - San Antonio San Antonio Texas United States 78229
29 Tyler Cardiovascular Consultants Tyler Texas United States 75701
30 Virginia Commonwealth University Richmond Virginia United States 23298
31 Local Institution Feldkirch Austria 6800
32 Local Institution Wien Austria 1090
33 Local Institution Wien Austria 1160
34 Local Institution Huy Luik Belgium 4500
35 Local Institution Aalst Belgium 9300
36 Local Institution Antwerpen Belgium 2020
37 Local Institution Brasschaat Belgium 2930
38 Local Institution Brugge Belgium 8000
39 Local Institution Brussels Belgium 1090
40 Local Institution Genk Belgium 3600
41 Local Institution Edmonton Alberta Canada T5H 3V9
42 Local Institution Edmonton Alberta Canada T6G 2B7
43 Local Institution Edmonton Alberta Canada T6K 4C1
44 Local Institution Victoria British Columbia Canada V8R 4R2
45 Local Institution St. John'S Newfoundland and Labrador Canada A1B 3V6
46 Local Institution Belleville Ontario Canada K8N1E6
47 Local Institution Chatham Ontario Canada N7L 1B9
48 Local Institution Hamilton Ontario Canada L8L 2X2
49 Local Institution London Ontario Canada N6A 5A5
50 Local Institution Oshawa Ontario Canada L1H 1B9
51 Local Institution Montreal Quebec Canada H1T 1C8
52 Local Institution Montreal Quebec Canada H1T 2M4
53 Local Institution Montreal Quebec Canada H2X 3J4
54 Local Institution St. Charles-Borromee Quebec Canada J6E 6J2
55 Local Institution Terrebonne Quebec Canada J6V 2H2
56 Local Institution Arhus C Denmark 8000
57 Local Institution Copenhagen Denmark 2100
58 Local Institution Esbjerg Denmark 6700
59 Local Institution Frederiksberg Denmark 2000
60 Local Institution Glostrup Denmark 2600
61 Local Institution Hellerup Denmark 2900
62 Local Institution Herning Denmark 7400
63 Local Institution Randers Denmark DK-8900
64 Local Institution Amiens Cedex 1 France 80054
65 Local Institution Cholet France 49300
66 Local Institution Dijon France 21079
67 Local Institution Nantes Cedex 01 France 44093
68 Local Institution Paris Cedex 13 France 75651
69 Local Institution Pessac Cedex France 33604
70 Local Institution Roubaix Cedex 1 France 59056
71 Local Institution Toulouse France 31403
72 Local Institution Berlin Germany 12351
73 Local Institution Berlin Germany 12559
74 Local Institution Duren Germany 52351
75 Local Institution Halle / Saale Germany 06120
76 Local Institution Hannover Germany 30625
77 Local Institution Krefeld Germany 47805
78 Local Institution Langen Germany 63225
79 Local Institution Ludwigshafen Germany 67063
80 Local Institution Witten Germany 58455
81 Local Institution Afula Israel 18101
82 Local Institution Hadera Israel 38100
83 Local Institution Haifa Israel 31096
84 Local Institution Haifa Israel 34362
85 Local Institution Jerusalem Israel 91031
86 Local Institution Jerusalem Israel 91120
87 Local Institution Jerusalem Israel 91240
88 Local Institution Kfar-Saba Israel 44281
89 Local Institution Nazareth Israel 16100
90 Local Institution Petach Tikva Israel 49100
91 Local Institution Rehovot Israel 76100
92 Local Institution Safed Israel 13100
93 Local Institution Tel Aviv Israel 64239
94 Local Institution Roma Italy 00168
95 Local Institution Bialystok Poland 15-276
96 Local Institution Bydgoszcz Poland 85-094
97 Local Institution Bydgoszcz Poland 85-168
98 Local Institution Bydgoszcz Poland 85-826
99 Local Institution Cracow Poland 31-202
100 Local Institution Gdansk Poland 80-952
101 Local Institution Katowice Poland 40-635
102 Local Institution Krakow Poland 31-501
103 Local Institution Lodz Poland 91-347
104 Local Institution Opole Poland 45-418
105 Local Institution Torun Poland 87-100
106 Local Institution Warszawa Poland 04-628
107 Local Institution Zielona Gora Poland 65-046
108 Local Institution Kemerovo Russian Federation 650002
109 Local Institution Moscow Russian Federation 105229
110 Local Institution Moscow Russian Federation 111020
111 Local Institution Moscow Russian Federation 115487
112 Local Institution Moscow Russian Federation 119620
113 Local Institution Moscow Russian Federation 121552
114 Local Institution Moscow Russian Federation 127473
115 Local Institution Moscow Russian Federation 129327
116 Local Institution Saint Petersburg Russian Federation 191104
117 Local Institution Saint Petersburg Russian Federation 193312
118 Local Institution Saint Petersburg Russian Federation 195067
119 Local Institution Saint Petersburg Russian Federation 197110
120 Local Institution Saratov Russian Federation 410028
121 Local Institution St. Petersburg Russian Federation 194156
122 Local Institution St.Petersburg Russian Federation 192242
123 Local Institution Yaroslavl Russian Federation 150003
124 Local Institution Yaroslav Russian Federation 150062
125 Local Institution Baracaldo (Vizcaya) Spain 48903
126 Local Institution Barcelona Spain 08035
127 Local Institution Hospitalet Llobregat Barcelona Spain 08907
128 Local Institution Leon Spain 24071
129 Local Institution Madrid Spain 28046
130 Local Institution Malaga Spain 29010
131 Local Institution Oviedo Spain 33006
132 Local Institution Santiago De Compostela Spain 15706
133 Local Institution Sevilla Spain 41071
134 Local Institution Tarragona Spain 43007
135 Local Institution Valladolid Spain 47010
136 Local Institution Villajoyosa Spain 03570
137 Local Institution Goteborg Sweden 413 45
138 Local Institution Goteborg Sweden SE-416 85
139 Local Institution Malmo Sweden 205 02
140 Local Institution Orebro Sweden 701 85
141 Local Institution Stockholm Sweden 141 86
142 Local Institution Sundsvall Sweden 851 86
143 Local Institution Uppsala Sweden 751 85
144 Local Institution Stockport Cheshire United Kingdom SK2 7JE
145 Local Institution Harrow Middlesex United Kingdom HA1 3UJ
146 Local Institution Edinburgh Midlothian United Kingdom EH16 4SB
147 Local Institution Portadown N. Ireland United Kingdom BT63 5QQ
148 Local Institution Sheffield South Yorkshire United Kingdom S10 2JF
149 Local Institution York Yorkshire United Kingdom YO31 8HE
150 Local Institution Croydon United Kingdom CR7 7YE
151 Local Institution Leicester United Kingdom LE3 9QP

Sponsors and Collaborators

  • Bristol-Myers Squibb

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:
NCT00313300
Other Study ID Numbers:
  • CV185-023
First Posted:
Apr 12, 2006
Last Update Posted:
Dec 30, 2015
Last Verified:
Nov 1, 2015
Additional relevant MeSH terms:
Acute Coronary Syndrome
Syndrome
Apixaban

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 1741 enrolled; 1715 randomized. Non-randomization reasons: 6 withdrew consent, 1 death, 1 poor/non-compliance, 18 no longer met study criteria. Phase A: placebo and 2 low doses of apixaban; Phase B: placebo, 2 low doses and 2 high doses of apixaban. High dose arms terminated, Phase B continued to enroll participants into placebo and low dose arms.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD
Arm/Group Description Study was conducted in 2 Phases (A and B). A tablet of Placebo along with ≤ 165 mg of aspirin was given daily for 26 weeks. 75 mg of clopidogrel once a day (QD) was allowed at the investigator's discretion. After 547 subjects were randomized to Phase A, an independent Data and Safety Monitoring Board (DSMB) recommended expanding the randomization to 2 higher doses of apixaban (10 mg BID and 20 mg QD) in Phase B of the study. Approximately 6 months after the start of Phase B, the DSMB recommended apixaban high dose groups be terminated due to excess bleeding in those participants receiving aspirin and clopidogrel concomitantly with high dose apixaban. Treatment and any new randomization into these 2 groups was halted, while randomization and treatment in the placebo and lower dose apixaban groups continued. Follow-up Period started after Week 26 through 30 days after discontinuation of study drug (for treated participants). In both Phase A and Phase B of the study: Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Follow-up Period started after Week 26 through 30 days after discontinuation of study drug (for treated participants). In both Phase A and Phase B of the study: Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Follow-up Period started after Week 26 through 30 days after discontinuation of study drug (for treated participants). Phase B of the Study: Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B, the DSMB recommended that the 10 mg BID QD group, be terminated due to excess bleeding for participants receiving aspirin and clopidogrel concomitantly with the 10 mg BID apixaban. Follow-up Period started after Week 26 through 30 days after discontinuation of study drug (for treated participants). Phase B of the Study: Tablet of Apixaban 20 mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B, the DSMB recommended that the apixaban 20 mg QD group, be terminated due to excess bleeding for participants receiving aspirin and clopidogrel concomitantly with the apixaban. Follow-up Period started after Week 26 through 30 days after discontinuation of study drug (for treated participants).
Period Title: Randomized in Phase A (26 Weeks)
STARTED 184 179 184 0 0
COMPLETED 130 140 149 0 0
NOT COMPLETED 54 39 35 0 0
Period Title: Randomized in Phase A (26 Weeks)
STARTED 427 138 134 248 221
Start of Phase B to High Dose Terminated 368 120 110 248 221
COMPLETED 333 105 94 15 13
NOT COMPLETED 94 33 40 233 208
Period Title: Randomized in Phase A (26 Weeks)
STARTED 163 162 174 0 0
COMPLETED 158 156 172 0 0
NOT COMPLETED 5 6 2 0 0
Period Title: Randomized in Phase A (26 Weeks)
STARTED 383 123 119 222 201
COMPLETED 380 123 117 217 199
NOT COMPLETED 3 0 2 5 2

Baseline Characteristics

Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD Total
Arm/Group Description Tablet of Placebo for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B, this treatment group was terminated Tablet of apixaban, oral, for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B, this treatment group was terminated. Total of all reporting groups
Overall Participants 611 317 318 248 221 1715
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
60.5
(11.25)
61.1
(11.64)
60.7
(11.35)
60.3
(11.00)
60.9
(11.95)
60.7
(11.38)
Age, Customized (participants) [Number]
Less than (<) 65 years
374
61.2%
187
59%
197
61.9%
165
66.5%
132
59.7%
1055
61.5%
Greater than, equal to 65 and < 75 years
170
27.8%
85
26.8%
82
25.8%
53
21.4%
57
25.8%
447
26.1%
Greater than (>) 75 years
67
11%
45
14.2%
39
12.3%
30
12.1%
32
14.5%
213
12.4%
Sex: Female, Male (Count of Participants)
Female
157
25.7%
75
23.7%
86
27%
45
18.1%
50
22.6%
413
24.1%
Male
454
74.3%
242
76.3%
232
73%
203
81.9%
171
77.4%
1302
75.9%
Region of Enrollment (participants) [Number]
Russian Federation
156
25.5%
93
29.3%
82
25.8%
59
23.8%
52
23.5%
442
25.8%
United States
69
11.3%
40
12.6%
44
13.8%
24
9.7%
14
6.3%
191
11.1%
United Kingdom
15
2.5%
7
2.2%
9
2.8%
5
2%
5
2.3%
41
2.4%
Spain
36
5.9%
11
3.5%
16
5%
17
6.9%
19
8.6%
99
5.8%
Canada
81
13.3%
47
14.8%
44
13.8%
26
10.5%
21
9.5%
219
12.8%
Austria
4
0.7%
2
0.6%
2
0.6%
4
1.6%
2
0.9%
14
0.8%
Sweden
42
6.9%
21
6.6%
24
7.5%
12
4.8%
12
5.4%
111
6.5%
Belgium
20
3.3%
11
3.5%
9
2.8%
10
4%
12
5.4%
62
3.6%
Poland
61
10%
21
6.6%
19
6%
34
13.7%
31
14%
166
9.7%
Denmark
16
2.6%
14
4.4%
15
4.7%
5
2%
4
1.8%
54
3.1%
Israel
55
9%
29
9.1%
32
10.1%
26
10.5%
21
9.5%
163
9.5%
France
21
3.4%
9
2.8%
8
2.5%
8
3.2%
10
4.5%
56
3.3%
Germany
34
5.6%
12
3.8%
14
4.4%
17
6.9%
18
8.1%
95
5.5%
Italy
1
0.2%
0
0%
0
0%
1
0.4%
0
0%
2
0.1%

Outcome Measures

1. Primary Outcome
Title Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses
Description Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The primary outcome is based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B. The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups (10mg BID, 20mg QD) and the resulting lower duration of exposure for these groups.
Time Frame From first dose of study drug (Day 1) to last dose plus 2 days, up to Year 2 of the Study

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of placebo or low dose apixaban. Due to the premature termination of the 2 apixaban high-dose groups (10 mg BID and 20 mg QD) in Phase B, the primary analyses reported are based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, less than, equal to (≤) 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Measure Participants 599 315 315
Number (95% Confidence Interval) [percentage of participants]
3.0
0.5%
5.7
1.8%
7.9
2.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted rate difference
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-1.0 to 5.4
Parameter Dispersion Type:
Value:
Estimation Comments adjusted difference of event rates takes into consideration stratification factors.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
0.4 to 7.3
Parameter Dispersion Type:
Value:
Estimation Comments adjusted difference of event rates takes into consideration stratification factors.
2. Secondary Outcome
Title Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants
Description Events were adjudicated by the Clinical Events Committee (CEC). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B.
Time Frame Randomization to 182 days after randomization (183 days)

Outcome Measure Data

Analysis Population Description
Participants who randomized to placebo or low dose apixaban are summarized. Due to the premature termination of the 2 apixaban high-dose groups (10 mg BID and 20 mg QD) in Phase B, the analyses reported are based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, less than, equal to (≤) 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Measure Participants 611 317 318
Number [participants]
53
8.7%
24
7.6%
19
6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.44 to 1.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.35 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses
Description Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events includes major bleeding, clinically relevant non-major bleeding and minor bleeding. Treatment Period refers to the period from first dose through 2 days, or through 30 days for Serious Adverse Event (SAE) tabulations, after discontinuation of study drug. Data in this outcome are combined across Phase A and Phase B.
Time Frame first dose (Day 1) to last dose plus 2 days (or for SAEs, plus 30 days), up to Year 2 of the Study

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of placebo or low dose apixaban are summarized. The analyses reported are based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, ≤165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Measure Participants 599 315 315
Number (95% Confidence Interval) [percentage of participants]
10.5
1.7%
20.6
6.5%
22.5
7.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted rate difference
Estimated Value 6.6
Confidence Interval (2-Sided) 95%
1.8 to 11.3
Parameter Dispersion Type:
Value:
Estimation Comments adjusted difference of event rates takes into consideration stratification factors.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
4.8 to 15.2
Parameter Dispersion Type:
Value:
Estimation Comments adjusted difference of event rates takes into consideration stratification factors.
4. Secondary Outcome
Title Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants
Description Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B
Time Frame Day of randomization to 182 days after day of randomization (183 days)

Outcome Measure Data

Analysis Population Description
Randomized participants were summarized.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, ≤165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Measure Participants 611 317 318
Number [participants]
54
8.8%
24
7.6%
20
6.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.44 to 1.17
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.37 to 1.07
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses
Description Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the Clinical Events Committee. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%).
Time Frame from first dose (Day 1) to last dose plus 2 days, up to Year 2 of the Study

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of placebo or low dose apixaban were analyzed.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, ≤165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion.
Measure Participants 599 315 315
Number (95% Confidence Interval) [percentage of participants]
0.8
0.1%
1.6
0.5%
1.9
0.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted rate difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.3 to 2.0
Parameter Dispersion Type:
Value:
Estimation Comments adjusted difference of event rates takes into consideration stratification factors.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.1 to 2.7
Parameter Dispersion Type:
Value:
Estimation Comments adjusted difference of event rates takes into consideration stratification factors.
6. Secondary Outcome
Title Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B
Description Phase B Adjusted Intended Treatment Period=day of randomization and ends on termination date of high dose apixaban, 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.
Time Frame Day of randomization and ends on high dose termination date, 1-Oct-2007

Outcome Measure Data

Analysis Population Description
Participants who were concomitantly randomized in Phase B only were summarized (start of Phase B, March 2007, to termination of high doses in Phase B, October 2007) .
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, ≤165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated. Tablet of apixaban QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated.
Measure Participants 368 120 110 248 221
Number [participants]
16
2.6%
6
1.9%
4
1.3%
8
3.2%
7
3.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.44 to 2.88
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.29 to 2.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.30 to 1.66
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 20 mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.30 to 1.74
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B
Description Bleeding was assessed using ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups and the lower duration of exposure. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).
Time Frame From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007

Outcome Measure Data

Analysis Population Description
Participants randomized in Phase B only who received at least one dose of placebo or apixaban were summarized.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD
Arm/Group Description Tablet of Placebo, oral, for 26 weeks. Also ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated. Tablet of apixaban QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated.
Measure Participants 362 119 108 244 218
Number (95% Confidence Interval) [percentage of participants]
0.8
0.1%
5.0
1.6%
5.6
1.8%
7.8
3.1%
7.3
3.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
0.0 to 8.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
0.0 to 9.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 7.0
Confidence Interval (2-Sided) 95%
3.4 to 10.5
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 20 mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
1.4 to 8.0
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B
Description Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events included major bleeding, clinically relevant non-major bleeding and minor bleeding. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).
Time Frame From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007

Outcome Measure Data

Analysis Population Description
Participants concomitantly randomized in Phase B who received at least one dose of placebo or apixaban were summarized.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated. Tablet of apixaban QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated.
Measure Participants 362 119 108 244 218
Number (95% Confidence Interval) [percentage of participants]
6.1
1%
15.1
4.8%
17.6
5.5%
24.2
9.8%
23.9
10.8%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 8.3
Confidence Interval (2-Sided) 95%
1.8 to 14.9
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
3.4 to 18.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 17.4
Confidence Interval (2-Sided) 95%
11.6 to 23.2
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 20 mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
5.6 to 15.1
Parameter Dispersion Type:
Value:
Estimation Comments
9. Secondary Outcome
Title Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B
Description Phase B Adjusted Intended Treatment Period=day of randomization and ends on 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.
Time Frame Day of randomization up to high dose termination, 1-Oct-2007

Outcome Measure Data

Analysis Population Description
Participants who were concomitantly randomized in Phase B were summarized.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also, ≤165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated. Tablet of apixaban QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated.
Measure Participants 368 120 110 248 221
Number [participants]
16
2.6%
6
1.9%
4
1.3%
8
3.2%
7
3.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.44 to 2.88
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.29 to 2.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.30 to 1.66
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 20 mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.30 to 1.74
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B
Description Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%).
Time Frame From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007

Outcome Measure Data

Analysis Population Description
Participants concomitantly randomized in Phase B who received at least one dose of placebo or apixaban were summarized.
Arm/Group Title Placebo Apixaban 2.5mg BID Apixaban 10mg QD Apixaban 10mg BID Apixaban 20 mg QD
Arm/Group Description Tablet of Placebo daily for 26 weeks. Also ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 2.5mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Tablet of Apixaban 10mg BID for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated. Tablet of apixaban QD for 26 weeks. Also, ≤ 165 mg of aspirin daily. 75 mg of clopidogrel QD was allowed at the investigator's discretion. Approximately 6 months after the start of Phase B this treatment group was terminated.
Measure Participants 362 119 108 244 218
Number (95% Confidence Interval) [percentage of participants]
0.0
0%
0.8
0.3%
0.0
0%
2.9
1.2%
4.1
1.9%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 2.5mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.9 to 2.6
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 10mg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
0.6 to 5.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 20 mg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Adjusted Rate Difference
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
1.3 to 6.9
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Day 1 up to 30 days post last dose of study drug, up to approximately 2 years: A+B treatment groups. March 2007 up to 30 days post last dose in October 2007 (termination of high doses), are presented in Phase B Treatment groups.
Adverse Event Reporting Description Participants treated with at least 1 dose of study drug are presented. Note: during Phase B, high dose apixaban arms (10 mg BID and 20 mg QD) were terminated but participants could continue to be randomized to Placebo, 2.5 mg BID and 10 mg QD apixaban and treated post termination of the high dose arms (October 2007), up to approximately 2 years.
Arm/Group Title Phase A+B Apixaban 10mg QD Phase A+B Apixaban 2.5mg BID Phase A+B Placebo Phase B Apixaban 10mg BID Phase B Apixaban 10mg QD Phase B Apixaban 20mg QD Phase B Apixaban 2.5mg BID Phase B Placebo
Arm/Group Description Total Phase A and Phase B participants combined who received at least 1 dose of 10 mg QD apixaban during the study. Total Phase A and Phase B participants combined who received at least 1 dose of 2.5 mg BID apixaban during the study. Total Phase A and Phase B participants combined who received at least 1 dose of placebo during the study. Participants treated with at least one dose of 10 mg BID apixaban during Phase B as measured from the start of randomization in Phase B and up to termination of high dose apixaban (October 2007) Participants treated with at least one dose of 10 mg QD apixaban during Phase B as measured from the start of randomization in Phase B and up to termination of high dose apixaban (October 2007) Participants treated with at least one dose of 20 mg QD apixaban during Phase B as measured from the start of randomization in Phase B and up to termination of high dose apixaban (October 2007) Participants treated with at least one dose of 2.5 mg BID apixaban during Phase B as measured from the start of randomization in Phase B and up to termination of high dose apixaban (October 2007) Participants treated with at least one dose of Placebo during Phase B as measured from the start of randomization in Phase B and up to termination of high dose apixaban (October 2007)
All Cause Mortality
Phase A+B Apixaban 10mg QD Phase A+B Apixaban 2.5mg BID Phase A+B Placebo Phase B Apixaban 10mg BID Phase B Apixaban 10mg QD Phase B Apixaban 20mg QD Phase B Apixaban 2.5mg BID Phase B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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) / (NaN) / (NaN)
Serious Adverse Events
Phase A+B Apixaban 10mg QD Phase A+B Apixaban 2.5mg BID Phase A+B Placebo Phase B Apixaban 10mg BID Phase B Apixaban 10mg QD Phase B Apixaban 20mg QD Phase B Apixaban 2.5mg BID Phase B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 72/315 (22.9%) 73/315 (23.2%) 125/599 (20.9%) 55/244 (22.5%) 22/108 (20.4%) 36/218 (16.5%) 19/119 (16%) 56/362 (15.5%)
Blood and lymphatic system disorders
Anaemia 1/315 (0.3%) 2/315 (0.6%) 0/599 (0%) 1/244 (0.4%) 1/108 (0.9%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Coagulopathy 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Cardiac disorders
Coronary artery disease 0/315 (0%) 1/315 (0.3%) 2/599 (0.3%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 1/362 (0.3%)
Coronary artery restenosis 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Ventricular tachycardia 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Angina pectoris 6/315 (1.9%) 8/315 (2.5%) 11/599 (1.8%) 5/244 (2%) 1/108 (0.9%) 3/218 (1.4%) 2/119 (1.7%) 4/362 (1.1%)
Angina unstable 5/315 (1.6%) 6/315 (1.9%) 14/599 (2.3%) 5/244 (2%) 2/108 (1.9%) 3/218 (1.4%) 0/119 (0%) 6/362 (1.7%)
Cardiac failure 3/315 (1%) 0/315 (0%) 4/599 (0.7%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 3/362 (0.8%)
Cardiac failure chronic 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Coronary artery stenosis 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Coronary artery dissection 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Acute myocardial infarction 1/315 (0.3%) 4/315 (1.3%) 4/599 (0.7%) 3/244 (1.2%) 0/108 (0%) 1/218 (0.5%) 1/119 (0.8%) 2/362 (0.6%)
Myocardial infarction 11/315 (3.5%) 8/315 (2.5%) 24/599 (4%) 3/244 (1.2%) 3/108 (2.8%) 1/218 (0.5%) 1/119 (0.8%) 12/362 (3.3%)
Myocardial ischaemia 0/315 (0%) 1/315 (0.3%) 5/599 (0.8%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 4/362 (1.1%)
Pericarditis 0/315 (0%) 2/315 (0.6%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 1/362 (0.3%)
Bundle branch block right 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Cardiac arrest 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Coronary artery occlusion 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Myocardial rupture 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Palpitations 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Tachyarrhythmia 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Bradycardia 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Cardiac failure acute 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Acute coronary syndrome 1/315 (0.3%) 1/315 (0.3%) 2/599 (0.3%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Cardiogenic shock 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Sick sinus syndrome 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Atrial fibrillation 4/315 (1.3%) 3/315 (1%) 3/599 (0.5%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 1/119 (0.8%) 2/362 (0.6%)
Atrial flutter 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Cardiac failure congestive 0/315 (0%) 3/315 (1%) 4/599 (0.7%) 2/244 (0.8%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 1/362 (0.3%)
Ventricular extrasystoles 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Ear and labyrinth disorders
Vertigo 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Ear haemorrhage 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Endocrine disorders
Hyperthyroidism 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Eye disorders
Eye haemorrhage 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Diplopia 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Gastrointestinal disorders
Gastrooesophageal reflux disease 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Duodenal ulcer haemorrhage 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Nausea 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Rectal haemorrhage 1/315 (0.3%) 1/315 (0.3%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Gastric ulcer haemorrhage 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Haematochezia 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Pancreatitis 0/315 (0%) 0/315 (0%) 2/599 (0.3%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Reflux oesophagitis 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Small intestinal obstruction 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Abdominal pain 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Constipation 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Gingival bleeding 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Barrett's oesophagus 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Haemorrhoidal haemorrhage 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Volvulus 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Abdominal symptom 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Colonic polyp 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Diabetic gastroparesis 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Gastric haemorrhage 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Gastritis 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Gastrointestinal haemorrhage 0/315 (0%) 1/315 (0.3%) 1/599 (0.2%) 3/244 (1.2%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Melaena 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Pancreatitis acute 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Upper gastrointestinal haemorrhage 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
General disorders
Chest pain 7/315 (2.2%) 6/315 (1.9%) 13/599 (2.2%) 7/244 (2.9%) 2/108 (1.9%) 6/218 (2.8%) 1/119 (0.8%) 8/362 (2.2%)
Impaired healing 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Malaise 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Chest discomfort 1/315 (0.3%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Sudden death 0/315 (0%) 3/315 (1%) 4/599 (0.7%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Asthenia 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Death 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Sudden cardiac death 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Catheter site haemorrhage 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Non-cardiac chest pain 6/315 (1.9%) 2/315 (0.6%) 4/599 (0.7%) 5/244 (2%) 3/108 (2.8%) 1/218 (0.5%) 0/119 (0%) 2/362 (0.6%)
Pyrexia 0/315 (0%) 2/315 (0.6%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 2/119 (1.7%) 0/362 (0%)
Infections and infestations
Appendicitis 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Bronchitis 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Gastroenteritis 1/315 (0.3%) 1/315 (0.3%) 1/599 (0.2%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Lower respiratory tract infection 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Postoperative wound infection 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Wound abscess 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Cellulitis 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Campylobacter gastroenteritis 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Endocarditis 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Erysipelas 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Pneumonia 0/315 (0%) 1/315 (0.3%) 3/599 (0.5%) 1/244 (0.4%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 1/362 (0.3%)
Septic shock 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Urinary tract infection 0/315 (0%) 0/315 (0%) 2/599 (0.3%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 2/362 (0.6%)
Peritonsillar abscess 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Injury, poisoning and procedural complications
Clavicle fracture 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
In-stent arterial restenosis 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Road traffic accident 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Femur fracture 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Foot fracture 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Incisional hernia 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Fibula fracture 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Tendon rupture 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Ankle fracture 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Lung injury 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Investigations
Electrocardiogram change 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Haemoglobin decreased 2/315 (0.6%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Arteriogram coronary 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Cardiac enzymes increased 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Metabolism and nutrition disorders
Hypercalcaemia 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Hyponatraemia 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Hyperkalaemia 0/315 (0%) 0/315 (0%) 0/599 (0%) 2/244 (0.8%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Diabetes mellitus 1/315 (0.3%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Hypoglycaemia 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Hyperglycaemia 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Arthropathy 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Intervertebral disc protrusion 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Musculoskeletal pain 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Pain in extremity 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Rhabdomyolysis 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Musculoskeletal chest pain 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Myalgia 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Spinal osteoarthritis 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Bladder cancer stage II 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Malignant melanoma 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Oesophageal carcinoma 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Basal cell carcinoma 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Bladder transitional cell carcinoma 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Rectal cancer 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Transitional cell carcinoma 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Colon cancer 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Cardiac myxoma 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Nervous system disorders
Dizziness 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Ischaemic stroke 0/315 (0%) 1/315 (0.3%) 2/599 (0.3%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Transient ischaemic attack 2/315 (0.6%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Dyskinesia 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Paraesthesia 0/315 (0%) 1/315 (0.3%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 1/362 (0.3%)
Presyncope 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Cerebrovascular accident 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Dementia Alzheimer's type 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Haemorrhage intracranial 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Hypoaesthesia 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Syncope vasovagal 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Headache 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Syncope 1/315 (0.3%) 2/315 (0.6%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Epilepsy 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Psychiatric disorders
Depression 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Hypomania 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Renal and urinary disorders
Nephrolithiasis 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Calculus ureteric 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Renal failure acute 0/315 (0%) 2/315 (0.6%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Acute prerenal failure 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Haematuria 2/315 (0.6%) 1/315 (0.3%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Renal failure 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Reproductive system and breast disorders
Uterine haemorrhage 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Uterine polyp 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Breast pain 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Vaginal haemorrhage 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 1/315 (0.3%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Epistaxis 0/315 (0%) 1/315 (0.3%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 2/218 (0.9%) 0/119 (0%) 1/362 (0.3%)
Haemoptysis 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 1/108 (0.9%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Chronic obstructive pulmonary disease 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Dyspnoea 0/315 (0%) 0/315 (0%) 3/599 (0.5%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Pulmonary embolism 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Pulmonary oedema 1/315 (0.3%) 1/315 (0.3%) 1/599 (0.2%) 0/244 (0%) 1/108 (0.9%) 1/218 (0.5%) 0/119 (0%) 1/362 (0.3%)
Skin and subcutaneous tissue disorders
Dermatitis allergic 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Lichen planus 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Toxic skin eruption 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Urticaria 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Skin ulcer 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Vascular disorders
Arterial restenosis 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Peripheral vascular disorder 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Arteriosclerosis 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Aneurysm 0/315 (0%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Ischaemia 8/315 (2.5%) 4/315 (1.3%) 12/599 (2%) 4/244 (1.6%) 2/108 (1.9%) 6/218 (2.8%) 1/119 (0.8%) 5/362 (1.4%)
Thrombosis 1/315 (0.3%) 0/315 (0%) 1/599 (0.2%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Angiopathy 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Haemorrhage 0/315 (0%) 3/315 (1%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Venous thrombosis limb 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Deep vein thrombosis 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 1/362 (0.3%)
Haematoma 1/315 (0.3%) 0/315 (0%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 1/218 (0.5%) 0/119 (0%) 0/362 (0%)
Hypertension 2/315 (0.6%) 3/315 (1%) 2/599 (0.3%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 1/119 (0.8%) 0/362 (0%)
Hypotension 0/315 (0%) 0/315 (0%) 0/599 (0%) 1/244 (0.4%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Intermittent claudication 0/315 (0%) 1/315 (0.3%) 0/599 (0%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Vascular pseudoaneurysm 0/315 (0%) 0/315 (0%) 1/599 (0.2%) 0/244 (0%) 0/108 (0%) 0/218 (0%) 0/119 (0%) 0/362 (0%)
Other (Not Including Serious) Adverse Events
Phase A+B Apixaban 10mg QD Phase A+B Apixaban 2.5mg BID Phase A+B Placebo Phase B Apixaban 10mg BID Phase B Apixaban 10mg QD Phase B Apixaban 20mg QD Phase B Apixaban 2.5mg BID Phase B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 122/315 (38.7%) 101/315 (32.1%) 175/599 (29.2%) 84/244 (34.4%) 30/108 (27.8%) 67/218 (30.7%) 22/119 (18.5%) 80/362 (22.1%)
Cardiac disorders
Angina pectoris 19/315 (6%) 18/315 (5.7%) 31/599 (5.2%) 10/244 (4.1%) 5/108 (4.6%) 11/218 (5%) 3/119 (2.5%) 12/362 (3.3%)
Gastrointestinal disorders
Gingival bleeding 11/315 (3.5%) 10/315 (3.2%) 9/599 (1.5%) 15/244 (6.1%) 2/108 (1.9%) 8/218 (3.7%) 4/119 (3.4%) 4/362 (1.1%)
General disorders
Chest pain 27/315 (8.6%) 21/315 (6.7%) 52/599 (8.7%) 19/244 (7.8%) 9/108 (8.3%) 14/218 (6.4%) 4/119 (3.4%) 24/362 (6.6%)
Fatigue 8/315 (2.5%) 13/315 (4.1%) 26/599 (4.3%) 16/244 (6.6%) 1/108 (0.9%) 6/218 (2.8%) 4/119 (3.4%) 14/362 (3.9%)
Injury, poisoning and procedural complications
Contusion 26/315 (8.3%) 20/315 (6.3%) 20/599 (3.3%) 12/244 (4.9%) 4/108 (3.7%) 10/218 (4.6%) 4/119 (3.4%) 10/362 (2.8%)
Nervous system disorders
Dizziness 18/315 (5.7%) 15/315 (4.8%) 35/599 (5.8%) 10/244 (4.1%) 4/108 (3.7%) 9/218 (4.1%) 3/119 (2.5%) 16/362 (4.4%)
Headache 25/315 (7.9%) 17/315 (5.4%) 30/599 (5%) 15/244 (6.1%) 2/108 (1.9%) 6/218 (2.8%) 0/119 (0%) 12/362 (3.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis 24/315 (7.6%) 18/315 (5.7%) 18/599 (3%) 16/244 (6.6%) 5/108 (4.6%) 25/218 (11.5%) 4/119 (3.4%) 2/362 (0.6%)
Dyspnoea 16/315 (5.1%) 13/315 (4.1%) 20/599 (3.3%) 3/244 (1.2%) 6/108 (5.6%) 4/218 (1.8%) 4/119 (3.4%) 10/362 (2.8%)
Vascular disorders
Haematoma 16/315 (5.1%) 11/315 (3.5%) 10/599 (1.7%) 9/244 (3.7%) 5/108 (4.6%) 9/218 (4.1%) 4/119 (3.4%) 5/362 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

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.

Results Point of Contact

Name/Title Bristol-Myers Squibb Study Director
Organization Bristol-Myers Squibb
Phone
Email Clinical.Trials@bms.com
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00313300
Other Study ID Numbers:
  • CV185-023
First Posted:
Apr 12, 2006
Last Update Posted:
Dec 30, 2015
Last Verified:
Nov 1, 2015