Trial Outcomes & Findings for A Phase 2b Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty (NCT NCT01203072)
NCT ID: NCT01203072
Last Updated: 2019-02-25
Results Overview
The primary efficacy endpoint was the proportion of subjects who experienced at least one of the thromboembolic events listed below during the period from the start of study treatment to the venography at the end of study treatment. * Lower extremity DVT confirmed by bilateral venography at the end of study treatment * Definite diagnosis of symptomatic PE * Symptomatic DVT confirmed before the venography at the end of study treatment The objectives were to verify the non-inferiority of edoxaban to enoxaparin with regard to prevention of VTE
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
523 participants
Primary outcome timeframe
2 weeks
Results posted on
2019-02-25
Participant Flow
Participant milestones
| Measure |
DU-176b 5 mg
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
105
|
106
|
104
|
106
|
102
|
|
Overall Study
COMPLETED
|
95
|
100
|
101
|
100
|
96
|
|
Overall Study
NOT COMPLETED
|
10
|
6
|
3
|
6
|
6
|
Reasons for withdrawal
| Measure |
DU-176b 5 mg
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
5
|
3
|
2
|
4
|
2
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
2
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
1
|
2
|
3
|
Baseline Characteristics
A Phase 2b Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty
Baseline characteristics by cohort
| Measure |
DU-176b 5 mg
n=88 Participants
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
n=92 Participants
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
n=88 Participants
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
n=88 Participants
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
n=89 Participants
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
Total
n=445 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
70.2 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
71.7 years
STANDARD_DEVIATION 7.0 • n=7 Participants
|
71.6 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
72.1 years
STANDARD_DEVIATION 7.0 • n=4 Participants
|
70.3 years
STANDARD_DEVIATION 6.5 • n=21 Participants
|
71.2 years
STANDARD_DEVIATION 7.3 • n=8 Participants
|
|
Sex: Female, Male
Female
|
67 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
347 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
98 Participants
n=8 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=8 Participants
|
|
Race (NIH/OMB)
Asian
|
88 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
88 Participants
n=4 Participants
|
89 Participants
n=21 Participants
|
445 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
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=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
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=8 Participants
|
|
Race (NIH/OMB)
White
|
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=8 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=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
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=8 Participants
|
|
Region of Enrollment
Japan
|
88 participants
n=5 Participants
|
92 participants
n=7 Participants
|
88 participants
n=5 Participants
|
88 participants
n=4 Participants
|
89 participants
n=21 Participants
|
445 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: The FAS was defined as all subjects enrolled in the study, but excluded those who had significant GCP violations, who had not received any doses of the study drug, or those who did not develop symptomatic DVT or PE, but in whom venography was not appropriately performed.
The primary efficacy endpoint was the proportion of subjects who experienced at least one of the thromboembolic events listed below during the period from the start of study treatment to the venography at the end of study treatment. * Lower extremity DVT confirmed by bilateral venography at the end of study treatment * Definite diagnosis of symptomatic PE * Symptomatic DVT confirmed before the venography at the end of study treatment The objectives were to verify the non-inferiority of edoxaban to enoxaparin with regard to prevention of VTE
Outcome measures
| Measure |
DU-176b 5 mg
n=88 Participants
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
n=92 Participants
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
n=88 Participants
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
n=88 Participants
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
n=89 Participants
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
|---|---|---|---|---|---|
|
Proportion of Subjects With Venous Thromboembolism Events.
|
29.5 percentage of participants
Interval 20.0 to 39.1
|
26.1 percentage of participants
Interval 17.1 to 35.1
|
12.5 percentage of participants
Interval 5.6 to 19.4
|
9.1 percentage of participants
Interval 3.1 to 15.1
|
48.3 percentage of participants
Interval 37.9 to 58.7
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: Safety Analysis Set is defined as subjects secondarily enrolled in study, but excluded those with significant GCP violations, did not receive any doses of study drug, or had no safety data after start of study treatment. Subjects with significant GCP violations, but received at least one dose of study drug, safety data were assessed individually
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding. Related to the study drug
Outcome measures
| Measure |
DU-176b 5 mg
n=103 Participants
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
n=106 Participants
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
n=103 Participants
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
n=106 Participants
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
n=102 Participants
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
|---|---|---|---|---|---|
|
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding
|
1.9 percentage of subjects with bleeds
Interval 0.5 to 6.8
|
3.8 percentage of subjects with bleeds
Interval 1.5 to 9.3
|
3.9 percentage of subjects with bleeds
Interval 1.5 to 9.6
|
4.7 percentage of subjects with bleeds
Interval 2.0 to 10.6
|
3.9 percentage of subjects with bleeds
Interval 1.5 to 9.7
|
Adverse Events
DU-176b 5 mg
Serious events: 2 serious events
Other events: 78 other events
Deaths: 0 deaths
DU-176b 15 mg
Serious events: 1 serious events
Other events: 85 other events
Deaths: 0 deaths
DU-176b 30 mg
Serious events: 1 serious events
Other events: 78 other events
Deaths: 0 deaths
DU-176b 60 mg
Serious events: 3 serious events
Other events: 78 other events
Deaths: 0 deaths
Placebo
Serious events: 5 serious events
Other events: 67 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
DU-176b 5 mg
n=103 participants at risk
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
n=106 participants at risk
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
n=103 participants at risk
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
n=106 participants at risk
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
n=102 participants at risk
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
|---|---|---|---|---|---|
|
Infections and infestations
nasopharyngitis
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.94%
1/106 • Number of events 1
|
0.00%
0/102
|
|
Ear and labyrinth disorders
vertigo positional
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.98%
1/102 • Number of events 1
|
|
Cardiac disorders
myocardial infarction
|
0.00%
0/103
|
0.00%
0/106
|
0.97%
1/103 • Number of events 1
|
0.00%
0/106
|
0.00%
0/102
|
|
Respiratory, thoracic and mediastinal disorders
asthma
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.94%
1/106 • Number of events 1
|
0.00%
0/102
|
|
Gastrointestinal disorders
rectal haemorrhage
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.98%
1/102 • Number of events 1
|
|
General disorders
pyrexia
|
0.97%
1/103 • Number of events 1
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/102
|
|
Investigations
platelet count decreased
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.98%
1/102 • Number of events 1
|
|
Injury, poisoning and procedural complications
compression fracture
|
0.97%
1/103 • Number of events 1
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
joint dislocation
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.94%
1/106 • Number of events 1
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
spinal compression fracture
|
0.00%
0/103
|
0.94%
1/106 • Number of events 1
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
tibia fracture
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.98%
1/102 • Number of events 1
|
|
Injury, poisoning and procedural complications
ligament rupture
|
0.00%
0/103
|
0.00%
0/106
|
0.00%
0/103
|
0.00%
0/106
|
0.98%
1/102 • Number of events 1
|
Other adverse events
| Measure |
DU-176b 5 mg
n=103 participants at risk
DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks
|
DU-176b 15 mg
n=106 participants at risk
DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks
|
DU-176b 30 mg
n=103 participants at risk
DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks
|
DU-176b 60 mg
n=106 participants at risk
DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks
|
Placebo
n=102 participants at risk
Placebo: Matching placebo oral tablets, once daily for 2 weeks
|
|---|---|---|---|---|---|
|
Infections and infestations
nasopharyngitis
|
6.8%
7/103 • Number of events 7
|
8.5%
9/106 • Number of events 9
|
9.7%
10/103 • Number of events 10
|
3.8%
4/106 • Number of events 4
|
7.8%
8/102 • Number of events 8
|
|
Psychiatric disorders
insomnia
|
1.9%
2/103 • Number of events 2
|
3.8%
4/106 • Number of events 4
|
7.8%
8/103 • Number of events 9
|
3.8%
4/106 • Number of events 4
|
4.9%
5/102 • Number of events 5
|
|
Nervous system disorders
headache
|
0.97%
1/103 • Number of events 1
|
4.7%
5/106 • Number of events 5
|
5.8%
6/103 • Number of events 6
|
1.9%
2/106 • Number of events 2
|
3.9%
4/102 • Number of events 4
|
|
Vascular disorders
wound haemorrhage
|
2.9%
3/103 • Number of events 3
|
1.9%
2/106 • Number of events 2
|
0.97%
1/103 • Number of events 1
|
5.7%
6/106 • Number of events 7
|
0.00%
0/102
|
|
Gastrointestinal disorders
constipation
|
4.9%
5/103 • Number of events 5
|
5.7%
6/106 • Number of events 6
|
3.9%
4/103 • Number of events 4
|
3.8%
4/106 • Number of events 4
|
4.9%
5/102 • Number of events 5
|
|
Gastrointestinal disorders
diarrhea
|
6.8%
7/103 • Number of events 7
|
2.8%
3/106 • Number of events 3
|
4.9%
5/103 • Number of events 5
|
3.8%
4/106 • Number of events 4
|
6.9%
7/102 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
dermatitis contact
|
3.9%
4/103 • Number of events 4
|
6.6%
7/106 • Number of events 7
|
1.9%
2/103 • Number of events 2
|
1.9%
2/106 • Number of events 2
|
0.98%
1/102 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
erythema
|
0.97%
1/103 • Number of events 1
|
2.8%
3/106 • Number of events 3
|
5.8%
6/103 • Number of events 6
|
2.8%
3/106 • Number of events 3
|
2.0%
2/102 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
heamorrhage subcutaneous
|
0.97%
1/103 • Number of events 1
|
3.8%
4/106 • Number of events 4
|
6.8%
7/103 • Number of events 7
|
4.7%
5/106 • Number of events 5
|
3.9%
4/102 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
pruritis
|
1.9%
2/103 • Number of events 2
|
4.7%
5/106 • Number of events 6
|
5.8%
6/103 • Number of events 8
|
0.94%
1/106 • Number of events 1
|
0.98%
1/102 • Number of events 1
|
|
Renal and urinary disorders
haematuria
|
1.9%
2/103 • Number of events 2
|
3.8%
4/106 • Number of events 4
|
0.97%
1/103 • Number of events 1
|
6.6%
7/106 • Number of events 8
|
0.00%
0/102
|
|
Investigations
alanine aminotransferase increased
|
6.8%
7/103 • Number of events 7
|
6.6%
7/106 • Number of events 7
|
6.8%
7/103 • Number of events 7
|
5.7%
6/106 • Number of events 6
|
7.8%
8/102 • Number of events 9
|
|
Investigations
aspartate aminotransferase increased
|
6.8%
7/103 • Number of events 7
|
6.6%
7/106 • Number of events 7
|
6.8%
7/103 • Number of events 7
|
3.8%
4/106 • Number of events 4
|
5.9%
6/102 • Number of events 6
|
|
Investigations
blood lactate dehydrogenase increased
|
12.6%
13/103 • Number of events 13
|
16.0%
17/106 • Number of events 17
|
15.5%
16/103 • Number of events 16
|
15.1%
16/106 • Number of events 17
|
11.8%
12/102 • Number of events 12
|
|
Investigations
gamma glutamyltransferase increased
|
9.7%
10/103 • Number of events 10
|
9.4%
10/106 • Number of events 10
|
6.8%
7/103 • Number of events 7
|
10.4%
11/106 • Number of events 11
|
6.9%
7/102 • Number of events 7
|
|
Investigations
blood urine present
|
5.8%
6/103 • Number of events 6
|
8.5%
9/106 • Number of events 10
|
8.7%
9/103 • Number of events 10
|
14.2%
15/106 • Number of events 16
|
5.9%
6/102 • Number of events 7
|
|
Investigations
haemoglobin decreased
|
2.9%
3/103 • Number of events 3
|
5.7%
6/106 • Number of events 6
|
5.8%
6/103 • Number of events 6
|
6.6%
7/106 • Number of events 7
|
4.9%
5/102 • Number of events 5
|
|
Investigations
platelet count increased
|
8.7%
9/103 • Number of events 9
|
13.2%
14/106 • Number of events 14
|
11.7%
12/103 • Number of events 12
|
5.7%
6/106 • Number of events 6
|
4.9%
5/102 • Number of events 5
|
|
Investigations
blood alkaline phosphate increased
|
10.7%
11/103 • Number of events 11
|
11.3%
12/106 • Number of events 12
|
8.7%
9/103 • Number of events 9
|
10.4%
11/106 • Number of events 11
|
8.8%
9/102 • Number of events 9
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI shall not publish the results of the Study at any time without the prior written approval of Sponsor.
- Publication restrictions are in place
Restriction type: OTHER