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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00504556
Recruitment Status : Completed
First Posted : July 20, 2007
Results First Posted : March 13, 2015
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Atrial Fibrillation
Thromboembolism
Interventions Drug: Edoxaban (DU-176b)
Drug: warfarin
Enrollment 1146
Recruitment Details  
Pre-assignment Details  
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablets two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Period Title: Overall Study
Started 235 245 235 180 251
Safety Analysis Set 235 244 234 180 250
Per Protocol Analysis Set 235 243 234 180 250
Pharmacodynamic Analysis Set 230 236 228 170 244
Completed 200 207 204 52 226
Not Completed 35 38 31 128 25
Reason Not Completed
Adverse Event             11             11             14             13             5
Death             3             3             1             0             2
Protocol Violation             1             3             2             1             2
Lost to Follow-up             0             0             1             1             1
Withdrawal by Subject             16             16             7             8             12
administrative reasons             0             2             2             1             2
did not meet entry criteria             2             0             1             1             0
data monitor committee decision             0             0             0             100             0
Other             2             2             2             3             0
not in safety analysis set             0             1             1             0             1
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets Total
Hide Arm/Group Description

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Total of all reporting groups
Overall Number of Baseline Participants 235 244 234 180 250 1143
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 235 participants 244 participants 234 participants 180 participants 250 participants 1143 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
109
  46.4%
119
  48.8%
105
  44.9%
83
  46.1%
97
  38.8%
513
  44.9%
>=65 years
126
  53.6%
125
  51.2%
129
  55.1%
97
  53.9%
153
  61.2%
630
  55.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 235 participants 244 participants 234 participants 180 participants 250 participants 1143 participants
65.2  (8.34) 64.8  (8.83) 64.9  (8.81) 64.7  (8.96) 66.0  (8.49) 64.9  (8.71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 235 participants 244 participants 234 participants 180 participants 250 participants 1143 participants
Female
95
  40.4%
94
  38.5%
79
  33.8%
66
  36.7%
99
  39.6%
433
  37.9%
Male
140
  59.6%
150
  61.5%
155
  66.2%
114
  63.3%
151
  60.4%
710
  62.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 235 participants 244 participants 234 participants 180 participants 250 participants 1143 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   0.4%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Native Hawaiian or Other Pacific Islander
1
   0.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Black or African American
1
   0.4%
0
   0.0%
1
   0.4%
0
   0.0%
0
   0.0%
2
   0.2%
White
230
  97.9%
239
  98.0%
228
  97.4%
176
  97.8%
243
  97.2%
1116
  97.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   1.3%
4
   1.6%
5
   2.1%
4
   2.2%
7
   2.8%
23
   2.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 235 participants 244 participants 234 participants 180 participants 250 participants 1143 participants
Belarus 5 5 6 1 5 22
United States 10 13 9 5 9 46
Slovakia 13 14 12 10 15 64
Mexico 2 3 3 3 4 15
Canada 2 3 2 2 2 11
Ukraine 77 80 81 70 83 391
Russian Federation 91 93 87 64 97 432
Chile 6 4 6 2 5 23
Latvia 5 6 6 4 6 27
Moldova, Republic of 11 12 11 11 12 57
Bosnia and Herzegovina 13 11 11 8 12 55
1.Primary Outcome
Title Adjudicated Incidence of Bleeding Events
Hide Description Adjudicated Incidence of Bleeding Events during treatment period
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
safety analysis set
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Overall Number of Participants Analyzed 235 244 234 180 250
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent of subjects with outcome event
All bleeding
5.5
(3.0 to 9.3)
12.7
(8.8 to 17.5)
7.3
(4.3 to 11.4)
18.3
(13.0 to 24.8)
8.0
(5.0 to 12.1)
Major or clinically relevant non-major bleed
3.0
(1.2 to 6.0)
7.8
(4.8 to 11.9)
3.8
(1.8 to 7.2)
10.6
(6.5 to 16.0)
3.2
(1.4 to 6.2)
Major bleed
0
(0 to 1.6)
2.0
(0.7 to 4.7)
0.4
(0 to 2.4)
3.3
(1.2 to 7.1)
0.4
(0 to 2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DU-176b 30mg qd, Warfarin Tablets
Comments All bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .367
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DU-176b 30mg Bid, Warfarin Tablets
Comments All bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .104
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DU-176b 60mg qd, Warfarin Tablets
Comments All bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .864
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DU-176b 60mg Bid, Warfarin Tablets
Comments All bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .002
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DU-176b 30mg qd, Warfarin Tablets
Comments Major or Clinically Relevant (CR) non-major bleeding
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DU-176b 30mg Bid, Warfarin Tablets
Comments Major or Clinically Relevant (CR) non-major bleeding
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DU-176b 60mg qd, Warfarin Tablets
Comments Major or Clinically Relevant (CR) non-major bleeding
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.807
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection DU-176b 60mg Bid, Warfarin Tablets
Comments Major or Clinically Relevant (CR) non-major bleeding
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection DU-176b 30mg qd, Warfarin Tablets
Comments Major bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection DU-176b 30mg Bid, Warfarin Tablets
Comments Major bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.119
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection DU-176b 60mg qd, Warfarin Tablets
Comments Major bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection DU-176b 60mg Bid, Warfarin Tablets
Comments Major bleeds
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
Hide Description liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
safety analysis set
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Overall Number of Participants Analyzed 235 244 234 180 250
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent subjects with liver related MA
ALT, total >= 3x ULN
1.3
(0.3 to 3.8)
0.9
(.01 to 3.0)
2.6
(1.0 to 5.6)
1.7
(0.4 to 5.0)
1.2
(0.3 to 3.5)
AST, total >= 3x ULN
0.9
(0.1 to 3.1)
0.9
(0.1 to 3.0)
1.3
(0.3 to 3.8)
1.2
(0.1 to 4.1)
0.8
(0.1 to 2.9)
total bilirubin, total >= 2x ULN
0.9
(0.1 to 3.1)
1.3
(0.3 to 3.7)
0.4
(0 to 2.4)
2.9
(1.0 to 6.7)
1.6
(0.4 to 4.1)
ALT or AST >=3 x ULN
1.3
(0.3 to 3.8)
0.9
(0.1 to 3.0)
3.1
(1.2 to 6.2)
1.7
(0.4 to 5.0)
1.6
(0.4 to 4.1)
ALT or AST >=3 x ULN and TBL >=2 x ULN
0
(0 to 1.6)
0.4
(0 to 2.3)
0
(0 to 1.6)
0.6
(0 to 3.2)
0
(0 to 1.5)
3.Secondary Outcome
Title Incidence of Major Adverse Cardiac Events MACE)
Hide Description 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
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
safety analysis set
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Overall Number of Participants Analyzed 235 244 234 180 250
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent of subjects experiencing events
MACE
1.7
(0.5 to 4.3)
2.5
(0.9 to 5.3)
4.3
(2.1 to 7.7)
1.1
(0.1 to 4.0)
2.4
(0.9 to 5.2)
any stroke
.4
(0 to 2.3)
.8
(.1 to 2.9)
.4
(0 to 2.4)
1.1
(0.1 to 4.0)
1.6
(0.4 to 4.0)
SEE
.4
(0 to 2.3)
.4
(0 to 2.3)
0
(0 to 1.6)
0
(0 to 2.0)
0
(0 to 1.5)
any stroke and/or SEE
.4
(0 to 2.3)
1.2
(.3 to 3.6)
.4
(0 to 2.4)
1.1
(0.1 to 4.0)
1.6
(.4 to 4.0)
MI
.9
(.1 to 3.0)
.4
(0 to 2.3)
.9
(.1 to 3.1)
0
(0 to 2.0)
0
(0 to 1.5)
CV death
.9
(.1 to 3.0)
1.6
(.4 to 4.1)
0
(0 to 1.6)
0
(0 to 2.0)
.8
(.1 to 2.9)
hospitalization for any cardiac condition
.9
(.1 to 3.0)
.8
(.1 to 2.9)
3.0
(1.2 to 6.1)
0
(0 to 2.0)
.4
(0 to 2.2)
4.Secondary Outcome
Title Effects on Biomarker D-dimer
Hide Description Mean (SD) change from baseline in D-dimer
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Overall Number of Participants Analyzed 213 218 215 156 230
Mean (Standard Deviation)
Unit of Measure: ng/mL
-225  (809.3) -187.8  (776.8) -100.5  (461.6) -129.8  (771.4) -160.7  (635.9)
5.Secondary Outcome
Title Effects on Biomarker Prothrombin Fragments
Hide Description Mean (SD) change from baseline in Prothrombin Fragments 1 and 2 (F1 and F2)
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

Overall Number of Participants Analyzed 209 217 209 151 223
Mean (Standard Deviation)
Unit of Measure: pmol/L
-23.5  (1312.0) -47.4  (1169.6) -51.4  (868.8) 6.4  (1353.8) -74.6  (849.5)
6.Secondary Outcome
Title Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Hide Description Median (min, max) values of Cmin,ss; Cmax,ss
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 235 244 234 180
Median (Full Range)
Unit of Measure: ng/mL
Cmin,ss (ng/mL)
10.3
(3.3 to 33.8)
21.2
(5.8 to 53.1)
39.6
(15.4 to 71.6)
75.7
(40.7 to 144.8)
Cmax,ss (ng/mL)
84.9
(48.9 to 178.8)
173.0
(106.7 to 338.5)
115.0
(72.9 to 240.0)
221.4
(162.9 to 400.1)
7.Secondary Outcome
Title Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b
Hide Description Median (min, max) values of AUCss
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 235 244 234 180
Median (Full Range)
Unit of Measure: ng*h/mL
825
(600 to 1862)
1729
(1176 to 3103)
1728
(1096 to 3125)
3301
(2485 to 5859)
8.Secondary Outcome
Title Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b
Hide Description Mean (SD) change from baseline in biomarker anti-Factor Xa [FXa] activity on Day 28, 1-3 hours post dose.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 185 199 184 109
Mean (Standard Deviation)
Unit of Measure: IU/mL
1.46  (.96) 1.91  (.97) 2.42  (1.63) 3.28  (1.46)
9.Secondary Outcome
Title Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b
Hide Description Mean (SD) change from baseline in biomarker endogenous FX activity on Day 28, 1-3 hours post dose.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 182 201 190 110
Mean (Standard Deviation)
Unit of Measure: percent change of Endogenous FX activity
-40.3  (26.4) -40.2  (25.5) -44.4  (25.7) -45.2  (26.7)
10.Secondary Outcome
Title Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b
Hide Description

Mean (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.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 181 196 180 110
Mean (Standard Deviation)
Unit of Measure: seconds
14.0  (5.2) 15.4  (5.6) 18.3  (11.9) 19.6  (6.4)
11.Secondary Outcome
Title Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b
Hide Description Mean (SD) change from baseline in biomarker prothrombin time (PT) on Day 28, 1-3 hours post dose.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 163 168 165 103
Mean (Standard Deviation)
Unit of Measure: seconds
0.6  (5.5) 0.4  (6.6) 2.0  (6.6) 2.1  (11.7)
12.Secondary Outcome
Title Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b
Hide Description Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid
Hide Arm/Group Description:

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

Overall Number of Participants Analyzed 163 168 165 103
Mean (Standard Deviation)
Unit of Measure: ratio
0.05  (.51) 0.03  (.62) 0.17  (.61) 0.26  (.61)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Hide Arm/Group Description

DU-176b 30mg tablet once daily (qd)

Edoxaban (DU-176b): 30mg tablet once daily

DU-176b 30mg twice daily (bid)

Edoxaban (DU-176b): 30mg tablet twice daily

DU-176b 60mg once daily (qd)

Edoxaban (DU-176b): 60mg tablet once daily

DU-176b 60mg tablet two times a day

Edoxaban (DU-176b): 60mg tablet two times a day

warfarin tablets

warfarin: warfarin tablets

All-Cause Mortality
DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/235 (4.26%)      16/244 (6.56%)      15/234 (6.41%)      14/180 (7.78%)      11/250 (4.40%)    
Blood and lymphatic system disorders           
anaemia  1  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
Cardiac disorders           
acute myocardial infarction  2  2/235 (0.85%)  2 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
angina unstable  2  1/235 (0.43%)  1 1/244 (0.41%)  1 3/234 (1.28%)  3 1/180 (0.56%)  1 0/250 (0.00%)  0
atrial fibrillation  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
cardiac failure  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
cardiac failure acute  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
cardiac failure congestive  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
cardiogenic shock  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
cardiomyopathy  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
cardiovascular disorder  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
coronary artery insufficiency  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
left ventricular failure  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
myocardial fibrosis  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
myocardial infarction  2  0/235 (0.00%)  0 0/244 (0.00%)  0 3/234 (1.28%)  3 0/180 (0.00%)  0 0/250 (0.00%)  0
ventricular fibrillation  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
Ear and labyrinth disorders           
deafness neurosensory  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
Gastrointestinal disorders           
gastric ulcer  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
gastric ulcer haemorrhage  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
gastroduodenal ulcer  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
gastrointestinal haemorrhage  2  0/235 (0.00%)  0 3/244 (1.23%)  4 0/234 (0.00%)  0 2/180 (1.11%)  2 0/250 (0.00%)  0
intestinal angina  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
intestinal obstruction  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
Hepatobiliary disorders           
cholecystitis  1  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
Infections and infestations           
haematoma infection  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
pneumonia  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
urinary tract infection  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
Injury, poisoning and procedural complications           
clavicle fracture  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
overdose  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
upper limb fracture  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
Investigations           
haemoglobin decreased  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
Metabolism and nutrition disorders           
diabetes mellitus  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
diabetes mellitus inadequate control  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
gout  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
gastric cancer  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
gastric neoplasm  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
Nervous system disorders           
cerebral artery thrombosis  1  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
cerebral haemorrhage  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 2/250 (0.80%)  2
diabetic neuropathy  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
dizziness  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
heamorrhage intracranial  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
haemorrhagic stroke  1  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
ischaemic stroke  2  3/235 (1.28%)  3 0/244 (0.00%)  0 0/234 (0.00%)  0 2/180 (1.11%)  2 3/250 (1.20%)  3
subarachnoid haemorrhage  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
transient ischaemic attack  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
Renal and urinary disorders           
haematuria  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  2 1/180 (0.56%)  1 0/250 (0.00%)  0
Reproductive system and breast disorders           
metrorrhagia  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
acute pulmonary oedema  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
dyspnoea  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
chronic obstructive pulmonary disease  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
epistaxis  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 1/250 (0.40%)  1
haemoptysis  2  0/235 (0.00%)  0 0/244 (0.00%)  0 0/234 (0.00%)  0 1/180 (0.56%)  1 0/250 (0.00%)  0
pulmonary embolism  2  1/235 (0.43%)  1 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
pulmonary oedema  2  1/235 (0.43%)  1 0/244 (0.00%)  0 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
Vascular disorders           
aortic aneurysm  2  0/235 (0.00%)  0 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
diabetic vascular disorder  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
haematoma  2  0/235 (0.00%)  0 1/244 (0.41%)  1 0/234 (0.00%)  0 0/180 (0.00%)  0 0/250 (0.00%)  0
hypertension  2  1/235 (0.43%)  1 0/244 (0.00%)  0 1/234 (0.43%)  1 0/180 (0.00%)  0 0/250 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA (10.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DU-176b 30mg qd DU-176b 30mg Bid DU-176b 60mg qd DU-176b 60mg Bid Warfarin Tablets
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/235 (1.28%)      8/244 (3.28%)      4/234 (1.71%)      10/180 (5.56%)      22/250 (8.80%)    
Investigations           
INR increased  1  0/235 (0.00%)  1/244 (0.41%)  2/234 (0.85%)  0/180 (0.00%)  18/250 (7.20%) 
Renal and urinary disorders           
hematuria  1  3/235 (1.28%)  7/244 (2.87%)  2/234 (0.85%)  10/180 (5.56%)  4/250 (1.60%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: William Maxwell, Assoc. Director
Organization: Daiichi Sankyo Inc.
Phone: 732-590-5000
EMail: wmaxwell@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00504556    
Other Study ID Numbers: DU176b-PRT018
First Submitted: July 18, 2007
First Posted: July 20, 2007
Results First Submitted: February 5, 2015
Results First Posted: March 13, 2015
Last Update Posted: February 26, 2019