Trial Outcomes & Findings for A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation (NCT NCT00504556)
NCT ID: NCT00504556
Last Updated: 2019-02-26
Results Overview
Adjudicated Incidence of Bleeding Events during treatment period
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
1146 participants
Primary outcome timeframe
3 months
Results posted on
2019-02-26
Participant Flow
Participant milestones
| Measure |
DU-176b 30mg qd
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
DU-176b 60mg tablets two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
235
|
245
|
235
|
180
|
251
|
|
Overall Study
Safety Analysis Set
|
235
|
244
|
234
|
180
|
250
|
|
Overall Study
Per Protocol Analysis Set
|
235
|
243
|
234
|
180
|
250
|
|
Overall Study
Pharmacodynamic Analysis Set
|
230
|
236
|
228
|
170
|
244
|
|
Overall Study
COMPLETED
|
200
|
207
|
204
|
52
|
226
|
|
Overall Study
NOT COMPLETED
|
35
|
38
|
31
|
128
|
25
|
Reasons for withdrawal
| Measure |
DU-176b 30mg qd
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
DU-176b 60mg tablets two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
11
|
11
|
14
|
13
|
5
|
|
Overall Study
Death
|
3
|
3
|
1
|
0
|
2
|
|
Overall Study
Protocol Violation
|
1
|
3
|
2
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
16
|
16
|
7
|
8
|
12
|
|
Overall Study
administrative reasons
|
0
|
2
|
2
|
1
|
2
|
|
Overall Study
did not meet entry criteria
|
2
|
0
|
1
|
1
|
0
|
|
Overall Study
data monitor committee decision
|
0
|
0
|
0
|
100
|
0
|
|
Overall Study
Other
|
2
|
2
|
2
|
3
|
0
|
|
Overall Study
not in safety analysis set
|
0
|
1
|
1
|
0
|
1
|
Baseline Characteristics
A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation
Baseline characteristics by cohort
| Measure |
DU-176b 30mg qd
n=235 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=250 Participants
warfarin tablets
warfarin: warfarin tablets
|
Total
n=1143 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
109 Participants
n=5 Participants
|
119 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
83 Participants
n=4 Participants
|
97 Participants
n=21 Participants
|
513 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
126 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
97 Participants
n=4 Participants
|
153 Participants
n=21 Participants
|
630 Participants
n=10 Participants
|
|
Age, Continuous
|
65.2 years
STANDARD_DEVIATION 8.34 • n=5 Participants
|
64.8 years
STANDARD_DEVIATION 8.83 • n=7 Participants
|
64.9 years
STANDARD_DEVIATION 8.81 • n=5 Participants
|
64.7 years
STANDARD_DEVIATION 8.96 • n=4 Participants
|
66.0 years
STANDARD_DEVIATION 8.49 • n=21 Participants
|
64.9 years
STANDARD_DEVIATION 8.71 • n=10 Participants
|
|
Sex: Female, Male
Female
|
95 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
66 Participants
n=4 Participants
|
99 Participants
n=21 Participants
|
433 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
140 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
155 Participants
n=5 Participants
|
114 Participants
n=4 Participants
|
151 Participants
n=21 Participants
|
710 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
230 Participants
n=5 Participants
|
239 Participants
n=7 Participants
|
228 Participants
n=5 Participants
|
176 Participants
n=4 Participants
|
243 Participants
n=21 Participants
|
1116 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
23 Participants
n=10 Participants
|
|
Region of Enrollment
Belarus
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
1 participants
n=4 Participants
|
5 participants
n=21 Participants
|
22 participants
n=10 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
13 participants
n=7 Participants
|
9 participants
n=5 Participants
|
5 participants
n=4 Participants
|
9 participants
n=21 Participants
|
46 participants
n=10 Participants
|
|
Region of Enrollment
Slovakia
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
12 participants
n=5 Participants
|
10 participants
n=4 Participants
|
15 participants
n=21 Participants
|
64 participants
n=10 Participants
|
|
Region of Enrollment
Mexico
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
4 participants
n=21 Participants
|
15 participants
n=10 Participants
|
|
Region of Enrollment
Canada
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
2 participants
n=21 Participants
|
11 participants
n=10 Participants
|
|
Region of Enrollment
Ukraine
|
77 participants
n=5 Participants
|
80 participants
n=7 Participants
|
81 participants
n=5 Participants
|
70 participants
n=4 Participants
|
83 participants
n=21 Participants
|
391 participants
n=10 Participants
|
|
Region of Enrollment
Russian Federation
|
91 participants
n=5 Participants
|
93 participants
n=7 Participants
|
87 participants
n=5 Participants
|
64 participants
n=4 Participants
|
97 participants
n=21 Participants
|
432 participants
n=10 Participants
|
|
Region of Enrollment
Chile
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
2 participants
n=4 Participants
|
5 participants
n=21 Participants
|
23 participants
n=10 Participants
|
|
Region of Enrollment
Latvia
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
4 participants
n=4 Participants
|
6 participants
n=21 Participants
|
27 participants
n=10 Participants
|
|
Region of Enrollment
Moldova, Republic of
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
11 participants
n=5 Participants
|
11 participants
n=4 Participants
|
12 participants
n=21 Participants
|
57 participants
n=10 Participants
|
|
Region of Enrollment
Bosnia and Herzegovina
|
13 participants
n=5 Participants
|
11 participants
n=7 Participants
|
11 participants
n=5 Participants
|
8 participants
n=4 Participants
|
12 participants
n=21 Participants
|
55 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: safety analysis set
Adjudicated Incidence of Bleeding Events during treatment period
Outcome measures
| Measure |
DU-176b 30mg qd
n=235 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=250 Participants
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Adjudicated Incidence of Bleeding Events
All bleeding
|
5.5 percent of subjects with outcome event
Interval 3.0 to 9.3
|
12.7 percent of subjects with outcome event
Interval 8.8 to 17.5
|
7.3 percent of subjects with outcome event
Interval 4.3 to 11.4
|
18.3 percent of subjects with outcome event
Interval 13.0 to 24.8
|
8.0 percent of subjects with outcome event
Interval 5.0 to 12.1
|
|
Adjudicated Incidence of Bleeding Events
Major or clinically relevant non-major bleed
|
3.0 percent of subjects with outcome event
Interval 1.2 to 6.0
|
7.8 percent of subjects with outcome event
Interval 4.8 to 11.9
|
3.8 percent of subjects with outcome event
Interval 1.8 to 7.2
|
10.6 percent of subjects with outcome event
Interval 6.5 to 16.0
|
3.2 percent of subjects with outcome event
Interval 1.4 to 6.2
|
|
Adjudicated Incidence of Bleeding Events
Major bleed
|
0 percent of subjects with outcome event
Interval 0.0 to 1.6
|
2.0 percent of subjects with outcome event
Interval 0.7 to 4.7
|
0.4 percent of subjects with outcome event
Interval 0.0 to 2.4
|
3.3 percent of subjects with outcome event
Interval 1.2 to 7.1
|
0.4 percent of subjects with outcome event
Interval 0.0 to 2.2
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: safety analysis set
liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities
Outcome measures
| Measure |
DU-176b 30mg qd
n=235 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=250 Participants
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
ALT, total >= 3x ULN
|
1.3 percent subjects with liver related MA
Interval 0.3 to 3.8
|
0.9 percent subjects with liver related MA
Interval 0.01 to 3.0
|
2.6 percent subjects with liver related MA
Interval 1.0 to 5.6
|
1.7 percent subjects with liver related MA
Interval 0.4 to 5.0
|
1.2 percent subjects with liver related MA
Interval 0.3 to 3.5
|
|
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
AST, total >= 3x ULN
|
0.9 percent subjects with liver related MA
Interval 0.1 to 3.1
|
0.9 percent subjects with liver related MA
Interval 0.1 to 3.0
|
1.3 percent subjects with liver related MA
Interval 0.3 to 3.8
|
1.2 percent subjects with liver related MA
Interval 0.1 to 4.1
|
0.8 percent subjects with liver related MA
Interval 0.1 to 2.9
|
|
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
total bilirubin, total >= 2x ULN
|
0.9 percent subjects with liver related MA
Interval 0.1 to 3.1
|
1.3 percent subjects with liver related MA
Interval 0.3 to 3.7
|
0.4 percent subjects with liver related MA
Interval 0.0 to 2.4
|
2.9 percent subjects with liver related MA
Interval 1.0 to 6.7
|
1.6 percent subjects with liver related MA
Interval 0.4 to 4.1
|
|
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
ALT or AST >=3 x ULN
|
1.3 percent subjects with liver related MA
Interval 0.3 to 3.8
|
0.9 percent subjects with liver related MA
Interval 0.1 to 3.0
|
3.1 percent subjects with liver related MA
Interval 1.2 to 6.2
|
1.7 percent subjects with liver related MA
Interval 0.4 to 5.0
|
1.6 percent subjects with liver related MA
Interval 0.4 to 4.1
|
|
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
ALT or AST >=3 x ULN and TBL >=2 x ULN
|
0 percent subjects with liver related MA
Interval 0.0 to 1.6
|
0.4 percent subjects with liver related MA
Interval 0.0 to 2.3
|
0 percent subjects with liver related MA
Interval 0.0 to 1.6
|
0.6 percent subjects with liver related MA
Interval 0.0 to 3.2
|
0 percent subjects with liver related MA
Interval 0.0 to 1.5
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: safety analysis set
MACE is defined as the composite of stroke \[ischemic or hemorrhagic\], Systemic embolic event (SEE), Myocardial Infarction (MI), Cardiovascular (CV) death, and hospitalization for any cardiac condition
Outcome measures
| Measure |
DU-176b 30mg qd
n=235 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=250 Participants
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Incidence of Major Adverse Cardiac Events MACE)
MACE
|
1.7 percent of subjects experiencing events
Interval 0.5 to 4.3
|
2.5 percent of subjects experiencing events
Interval 0.9 to 5.3
|
4.3 percent of subjects experiencing events
Interval 2.1 to 7.7
|
1.1 percent of subjects experiencing events
Interval 0.1 to 4.0
|
2.4 percent of subjects experiencing events
Interval 0.9 to 5.2
|
|
Incidence of Major Adverse Cardiac Events MACE)
any stroke
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.3
|
.8 percent of subjects experiencing events
Interval 0.1 to 2.9
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.4
|
1.1 percent of subjects experiencing events
Interval 0.1 to 4.0
|
1.6 percent of subjects experiencing events
Interval 0.4 to 4.0
|
|
Incidence of Major Adverse Cardiac Events MACE)
SEE
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.3
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.3
|
0 percent of subjects experiencing events
Interval 0.0 to 1.6
|
0 percent of subjects experiencing events
Interval 0.0 to 2.0
|
0 percent of subjects experiencing events
Interval 0.0 to 1.5
|
|
Incidence of Major Adverse Cardiac Events MACE)
any stroke and/or SEE
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.3
|
1.2 percent of subjects experiencing events
Interval 0.3 to 3.6
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.4
|
1.1 percent of subjects experiencing events
Interval 0.1 to 4.0
|
1.6 percent of subjects experiencing events
Interval 0.4 to 4.0
|
|
Incidence of Major Adverse Cardiac Events MACE)
MI
|
.9 percent of subjects experiencing events
Interval 0.1 to 3.0
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.3
|
.9 percent of subjects experiencing events
Interval 0.1 to 3.1
|
0 percent of subjects experiencing events
Interval 0.0 to 2.0
|
0 percent of subjects experiencing events
Interval 0.0 to 1.5
|
|
Incidence of Major Adverse Cardiac Events MACE)
CV death
|
.9 percent of subjects experiencing events
Interval 0.1 to 3.0
|
1.6 percent of subjects experiencing events
Interval 0.4 to 4.1
|
0 percent of subjects experiencing events
Interval 0.0 to 1.6
|
0 percent of subjects experiencing events
Interval 0.0 to 2.0
|
.8 percent of subjects experiencing events
Interval 0.1 to 2.9
|
|
Incidence of Major Adverse Cardiac Events MACE)
hospitalization for any cardiac condition
|
.9 percent of subjects experiencing events
Interval 0.1 to 3.0
|
.8 percent of subjects experiencing events
Interval 0.1 to 2.9
|
3.0 percent of subjects experiencing events
Interval 1.2 to 6.1
|
0 percent of subjects experiencing events
Interval 0.0 to 2.0
|
.4 percent of subjects experiencing events
Interval 0.0 to 2.2
|
SECONDARY outcome
Timeframe: 3 monthsMean (SD) change from baseline in D-dimer
Outcome measures
| Measure |
DU-176b 30mg qd
n=213 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=218 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=215 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=156 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=230 Participants
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Biomarker D-dimer
|
-225 ng/mL
Standard Deviation 809.3
|
-187.8 ng/mL
Standard Deviation 776.8
|
-100.5 ng/mL
Standard Deviation 461.6
|
-129.8 ng/mL
Standard Deviation 771.4
|
-160.7 ng/mL
Standard Deviation 635.9
|
SECONDARY outcome
Timeframe: 3 monthsMean (SD) change from baseline in Prothrombin Fragments 1 and 2 (F1 and F2)
Outcome measures
| Measure |
DU-176b 30mg qd
n=209 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=217 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=209 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=151 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=223 Participants
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Biomarker Prothrombin Fragments
|
-23.5 pmol/L
Standard Deviation 1312.0
|
-47.4 pmol/L
Standard Deviation 1169.6
|
-51.4 pmol/L
Standard Deviation 868.8
|
6.4 pmol/L
Standard Deviation 1353.8
|
-74.6 pmol/L
Standard Deviation 849.5
|
SECONDARY outcome
Timeframe: 3 monthsMedian (min, max) values of Cmin,ss; Cmax,ss
Outcome measures
| Measure |
DU-176b 30mg qd
n=235 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Cmin,ss (ng/mL)
|
10.3 ng/mL
Interval 3.3 to 33.8
|
21.2 ng/mL
Interval 5.8 to 53.1
|
39.6 ng/mL
Interval 15.4 to 71.6
|
75.7 ng/mL
Interval 40.7 to 144.8
|
—
|
|
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Cmax,ss (ng/mL)
|
84.9 ng/mL
Interval 48.9 to 178.8
|
173.0 ng/mL
Interval 106.7 to 338.5
|
115.0 ng/mL
Interval 72.9 to 240.0
|
221.4 ng/mL
Interval 162.9 to 400.1
|
—
|
SECONDARY outcome
Timeframe: 3 monthsMedian (min, max) values of AUCss
Outcome measures
| Measure |
DU-176b 30mg qd
n=235 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b
|
825 ng*h/mL
Interval 600.0 to 1862.0
|
1729 ng*h/mL
Interval 1176.0 to 3103.0
|
1728 ng*h/mL
Interval 1096.0 to 3125.0
|
3301 ng*h/mL
Interval 2485.0 to 5859.0
|
—
|
SECONDARY outcome
Timeframe: Day 28Mean (SD) change from baseline in biomarker anti-Factor Xa \[FXa\] activity on Day 28, 1-3 hours post dose.
Outcome measures
| Measure |
DU-176b 30mg qd
n=185 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=199 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=184 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=109 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b
|
1.46 IU/mL
Standard Deviation .96
|
1.91 IU/mL
Standard Deviation .97
|
2.42 IU/mL
Standard Deviation 1.63
|
3.28 IU/mL
Standard Deviation 1.46
|
—
|
SECONDARY outcome
Timeframe: Day 28Mean (SD) change from baseline in biomarker endogenous FX activity on Day 28, 1-3 hours post dose.
Outcome measures
| Measure |
DU-176b 30mg qd
n=182 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=201 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=190 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=110 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b
|
-40.3 percent change of Endogenous FX activity
Standard Deviation 26.4
|
-40.2 percent change of Endogenous FX activity
Standard Deviation 25.5
|
-44.4 percent change of Endogenous FX activity
Standard Deviation 25.7
|
-45.2 percent change of Endogenous FX activity
Standard Deviation 26.7
|
—
|
SECONDARY outcome
Timeframe: Day 28Mean (SD) change from baseline in biomarker prothrombinase induced clotting time \[PICT\] on Day 28, 1-3 hours post dose. PICT was determined by PICT aasay which is a plasma based functional assay to determine the anticoagulant activity on FXa and FIIa inhibition.
Outcome measures
| Measure |
DU-176b 30mg qd
n=181 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=196 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=180 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=110 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b
|
14.0 seconds
Standard Deviation 5.2
|
15.4 seconds
Standard Deviation 5.6
|
18.3 seconds
Standard Deviation 11.9
|
19.6 seconds
Standard Deviation 6.4
|
—
|
SECONDARY outcome
Timeframe: Day 28Mean (SD) change from baseline in biomarker prothrombin time (PT) on Day 28, 1-3 hours post dose.
Outcome measures
| Measure |
DU-176b 30mg qd
n=163 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=168 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=165 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=103 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b
|
0.6 seconds
Standard Deviation 5.5
|
0.4 seconds
Standard Deviation 6.6
|
2.0 seconds
Standard Deviation 6.6
|
2.1 seconds
Standard Deviation 11.7
|
—
|
SECONDARY outcome
Timeframe: Day 28Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.
Outcome measures
| Measure |
DU-176b 30mg qd
n=163 Participants
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=168 Participants
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=165 Participants
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=103 Participants
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b
|
0.05 ratio
Standard Deviation .51
|
0.03 ratio
Standard Deviation .62
|
0.17 ratio
Standard Deviation .61
|
0.26 ratio
Standard Deviation .61
|
—
|
Adverse Events
DU-176b 30mg qd
Serious events: 10 serious events
Other events: 3 other events
Deaths: 0 deaths
DU-176b 30mg Bid
Serious events: 16 serious events
Other events: 8 other events
Deaths: 0 deaths
DU-176b 60mg qd
Serious events: 15 serious events
Other events: 4 other events
Deaths: 0 deaths
DU-176b 60mg Bid
Serious events: 14 serious events
Other events: 10 other events
Deaths: 0 deaths
Warfarin Tablets
Serious events: 11 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
DU-176b 30mg qd
n=235 participants at risk
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 participants at risk
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 participants at risk
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 participants at risk
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=250 participants at risk
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
anaemia
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Cardiac disorders
acute myocardial infarction
|
0.85%
2/235 • Number of events 2
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
angina unstable
|
0.43%
1/235 • Number of events 1
|
0.41%
1/244 • Number of events 1
|
1.3%
3/234 • Number of events 3
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Cardiac disorders
atrial fibrillation
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Cardiac disorders
cardiac failure
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
cardiac failure acute
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
cardiac failure congestive
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Cardiac disorders
cardiogenic shock
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
cardiomyopathy
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
cardiovascular disorder
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Cardiac disorders
coronary artery insufficiency
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
left ventricular failure
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
myocardial fibrosis
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
myocardial infarction
|
0.00%
0/235
|
0.00%
0/244
|
1.3%
3/234 • Number of events 3
|
0.00%
0/180
|
0.00%
0/250
|
|
Cardiac disorders
ventricular fibrillation
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Ear and labyrinth disorders
deafness neurosensory
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Gastrointestinal disorders
gastric ulcer
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Gastrointestinal disorders
gastric ulcer haemorrhage
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Gastrointestinal disorders
gastroduodenal ulcer
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Gastrointestinal disorders
gastrointestinal haemorrhage
|
0.00%
0/235
|
1.2%
3/244 • Number of events 4
|
0.00%
0/234
|
1.1%
2/180 • Number of events 2
|
0.00%
0/250
|
|
Gastrointestinal disorders
intestinal angina
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Gastrointestinal disorders
intestinal obstruction
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Hepatobiliary disorders
cholecystitis
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Infections and infestations
haematoma infection
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Infections and infestations
pneumonia
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Infections and infestations
urinary tract infection
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Injury, poisoning and procedural complications
clavicle fracture
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Injury, poisoning and procedural complications
overdose
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Injury, poisoning and procedural complications
upper limb fracture
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Investigations
haemoglobin decreased
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Metabolism and nutrition disorders
diabetes mellitus
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Metabolism and nutrition disorders
diabetes mellitus inadequate control
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Metabolism and nutrition disorders
gout
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
gastric cancer
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
gastric neoplasm
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Nervous system disorders
cerebral artery thrombosis
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Nervous system disorders
cerebral haemorrhage
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.80%
2/250 • Number of events 2
|
|
Nervous system disorders
diabetic neuropathy
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Nervous system disorders
dizziness
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Nervous system disorders
heamorrhage intracranial
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Nervous system disorders
haemorrhagic stroke
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Nervous system disorders
ischaemic stroke
|
1.3%
3/235 • Number of events 3
|
0.00%
0/244
|
0.00%
0/234
|
1.1%
2/180 • Number of events 2
|
1.2%
3/250 • Number of events 3
|
|
Nervous system disorders
subarachnoid haemorrhage
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Nervous system disorders
transient ischaemic attack
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Renal and urinary disorders
haematuria
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 2
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Reproductive system and breast disorders
metrorrhagia
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Respiratory, thoracic and mediastinal disorders
acute pulmonary oedema
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Respiratory, thoracic and mediastinal disorders
dyspnoea
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Respiratory, thoracic and mediastinal disorders
chronic obstructive pulmonary disease
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.40%
1/250 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
haemoptysis
|
0.00%
0/235
|
0.00%
0/244
|
0.00%
0/234
|
0.56%
1/180 • Number of events 1
|
0.00%
0/250
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
0.43%
1/235 • Number of events 1
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary oedema
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Vascular disorders
aortic aneurysm
|
0.00%
0/235
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
|
Vascular disorders
diabetic vascular disorder
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Vascular disorders
haematoma
|
0.00%
0/235
|
0.41%
1/244 • Number of events 1
|
0.00%
0/234
|
0.00%
0/180
|
0.00%
0/250
|
|
Vascular disorders
hypertension
|
0.43%
1/235 • Number of events 1
|
0.00%
0/244
|
0.43%
1/234 • Number of events 1
|
0.00%
0/180
|
0.00%
0/250
|
Other adverse events
| Measure |
DU-176b 30mg qd
n=235 participants at risk
DU-176b 30mg tablet once daily (qd)
Edoxaban (DU-176b): 30mg tablet once daily
|
DU-176b 30mg Bid
n=244 participants at risk
DU-176b 30mg twice daily (bid)
Edoxaban (DU-176b): 30mg tablet twice daily
|
DU-176b 60mg qd
n=234 participants at risk
DU-176b 60mg once daily (qd)
Edoxaban (DU-176b): 60mg tablet once daily
|
DU-176b 60mg Bid
n=180 participants at risk
DU-176b 60mg tablet two times a day
Edoxaban (DU-176b): 60mg tablet two times a day
|
Warfarin Tablets
n=250 participants at risk
warfarin tablets
warfarin: warfarin tablets
|
|---|---|---|---|---|---|
|
Investigations
INR increased
|
0.00%
0/235
|
0.41%
1/244
|
0.85%
2/234
|
0.00%
0/180
|
7.2%
18/250
|
|
Renal and urinary disorders
hematuria
|
1.3%
3/235
|
2.9%
7/244
|
0.85%
2/234
|
5.6%
10/180
|
1.6%
4/250
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A study site may not publish results of a study until after a coordinated multicenter publication has been submitted for publication or until one year after the study has ended, whichever occurs first. The study site will have the opportunity to publish results of the study, provided Daiichi Sankyo has had the opportunity to review and comment on the study site's proposed publication prior to being submitted for publication with the advice of patent council and need for subject protection.
- Publication restrictions are in place
Restriction type: OTHER