Trial Outcomes & Findings for Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation (NCT NCT00829933)
NCT ID: NCT00829933
Last Updated: 2019-02-25
Results Overview
The primary endpoint was the incidence of bleeding events (major bleeding, clinically relevant non-major bleeding, or minor bleeding) that occurred during the treatment period.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
536 participants
Primary outcome timeframe
12 weeks
Results posted on
2019-02-25
Participant Flow
Participant milestones
| Measure |
DU-176b Low Dose 30mg
DU-176b tablets:
DU-176b tablets taken once daily for 12 weeks
|
DU-176b Intermediate Dose 45mg
DU-176b tablets:
DU-176b tablets taken once daily for 12 weeks
|
DU-176b High Dose 60mg
DU-176b tablets:
DU-176b tablets taken once daily for 12 weeks
|
Warfarin
Warfarin potassium tablets:
Warfarin potassium tablets taken once daily for 12 weeks while adjusting dose
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
135
|
135
|
132
|
134
|
|
Overall Study
Baseline Analysis Population
|
131
|
134
|
131
|
129
|
|
Overall Study
COMPLETED
|
121
|
122
|
119
|
120
|
|
Overall Study
NOT COMPLETED
|
14
|
13
|
13
|
14
|
Reasons for withdrawal
| Measure |
DU-176b Low Dose 30mg
DU-176b tablets:
DU-176b tablets taken once daily for 12 weeks
|
DU-176b Intermediate Dose 45mg
DU-176b tablets:
DU-176b tablets taken once daily for 12 weeks
|
DU-176b High Dose 60mg
DU-176b tablets:
DU-176b tablets taken once daily for 12 weeks
|
Warfarin
Warfarin potassium tablets:
Warfarin potassium tablets taken once daily for 12 weeks while adjusting dose
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
2
|
1
|
|
Overall Study
Death
|
0
|
0
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
0
|
0
|
|
Overall Study
Physician Decision
|
5
|
7
|
8
|
1
|
|
Overall Study
Pregnancy
|
0
|
0
|
0
|
2
|
|
Overall Study
Protocol Violation
|
2
|
1
|
0
|
0
|
|
Overall Study
withdrew before treatment started
|
5
|
1
|
2
|
9
|
Baseline Characteristics
Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation
Baseline characteristics by cohort
| Measure |
DU-176b Low Dose 30mg
n=131 Participants
DU-176b tablets taken once daily for 12 weeks
|
DU-176b Intermediate Dose 45mg
n=134 Participants
DU-176b tablets taken once daily for 12 weeks
|
DU-176b High Dose 60mg
n=131 Participants
DU-176b tablets taken once daily for 12 weeks
|
Warfarin
n=129 Participants
Warfarin potassium tablets taken once daily for 12 weeks while adjusting dose
|
Total
n=525 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
69.4 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
69.5 years
STANDARD_DEVIATION 8.8 • n=7 Participants
|
68.4 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
68.8 years
STANDARD_DEVIATION 8.2 • n=4 Participants
|
69.0 years
STANDARD_DEVIATION 8.2 • n=21 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
92 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
110 Participants
n=5 Participants
|
109 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
107 Participants
n=4 Participants
|
433 Participants
n=21 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
|
|
Race (NIH/OMB)
Asian
|
131 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
129 Participants
n=4 Participants
|
525 Participants
n=21 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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
Region of Enrollment
Japan
|
131 participants
n=5 Participants
|
134 participants
n=7 Participants
|
131 participants
n=5 Participants
|
129 participants
n=4 Participants
|
525 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Primary endpoint analyzed for subjects who proceeded to treatment period in FAS.
The primary endpoint was the incidence of bleeding events (major bleeding, clinically relevant non-major bleeding, or minor bleeding) that occurred during the treatment period.
Outcome measures
| Measure |
DU-176b Low Dose 30mg
n=130 Participants
DU-176b tablets taken once daily for 12 weeks
|
DU-176b Intermediate Dose 45mg
n=134 Participants
DU-176b tablets taken once daily for 12 weeks
|
DU-176b High Dose 60mg
n=130 Participants
DU-176b tablets taken once daily for 12 weeks
|
Warfarin
n=125 Participants
Warfarin potassium tablets taken once daily for 12 weeks while adjusting dose
|
|---|---|---|---|---|
|
Incidence of Bleeding Events (Major Bleeding, Clinically Relevant Non-major Bleeding and Minor Bleeding ) Identified During the Period From the Entry Into the Treatment Period Until Completion or Termination of the Treatment.
|
18.5 percent of subjects with bleeding event
Interval 12.7 to 26.0
|
22.4 percent of subjects with bleeding event
Interval 16.2 to 30.2
|
27.7 percent of subjects with bleeding event
Interval 20.7 to 35.9
|
20.0 percent of subjects with bleeding event
Interval 13.9 to 27.9
|
SECONDARY outcome
Timeframe: 12 weeksOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeksOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeksPT - prothrombin time INR - International Normalized Ratio APTT - Activated Partial Thromboplastin time
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeksOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeksOutcome measures
Outcome data not reported
Adverse Events
DU-176b Low Dose 30mg
Serious events: 4 serious events
Other events: 85 other events
Deaths: 0 deaths
DU-176b Intermediate Dose 45mg
Serious events: 2 serious events
Other events: 103 other events
Deaths: 0 deaths
DU-176b High Dose 60mg
Serious events: 2 serious events
Other events: 103 other events
Deaths: 0 deaths
Warfarin
Serious events: 7 serious events
Other events: 88 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
DU-176b Low Dose 30mg
n=130 participants at risk
DU-176b tablets taken once daily for 12 weeks
|
DU-176b Intermediate Dose 45mg
n=134 participants at risk
DU-176b tablets taken once daily for 12 weeks
|
DU-176b High Dose 60mg
n=130 participants at risk
DU-176b tablets taken once daily for 12 weeks
|
Warfarin
n=125 participants at risk
Warfarin potassium tablets taken once daily for 12 weeks while adjusting dose
|
|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
colon cancer
|
0.00%
0/130
|
0.75%
1/134 • Number of events 1
|
0.00%
0/130
|
0.00%
0/125
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
metastases to spine
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
Nervous system disorders
cerebral haemorrhage
|
0.00%
0/130
|
0.00%
0/134
|
0.77%
1/130 • Number of events 1
|
0.00%
0/125
|
|
Nervous system disorders
cerebral infarction
|
0.00%
0/130
|
0.75%
1/134 • Number of events 1
|
0.00%
0/130
|
0.00%
0/125
|
|
Nervous system disorders
transient ischemic attack
|
0.77%
1/130 • Number of events 1
|
0.00%
0/134
|
0.00%
0/130
|
0.00%
0/125
|
|
Cardiac disorders
atrial fibrillation
|
0.77%
1/130 • Number of events 1
|
0.00%
0/134
|
0.00%
0/130
|
0.00%
0/125
|
|
Cardiac disorders
cardiac failure
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
Cardiac disorders
cardiac failure congestive
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
interstitial lung disease
|
0.77%
1/130 • Number of events 1
|
0.00%
0/134
|
0.00%
0/130
|
0.00%
0/125
|
|
Infections and infestations
upper respiratory tract infection
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
Renal and urinary disorders
haematuria
|
0.00%
0/130
|
0.00%
0/134
|
0.77%
1/130 • Number of events 1
|
0.00%
0/125
|
|
Renal and urinary disorders
nephrotic syndrome
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
Reproductive system and breast disorders
benign prostatic hyperplasia
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
General disorders
sudden death
|
0.00%
0/130
|
0.00%
0/134
|
0.00%
0/130
|
0.80%
1/125 • Number of events 1
|
|
Injury, poisoning and procedural complications
tooth fracture
|
0.77%
1/130 • Number of events 1
|
0.00%
0/134
|
0.00%
0/130
|
0.00%
0/125
|
Other adverse events
| Measure |
DU-176b Low Dose 30mg
n=130 participants at risk
DU-176b tablets taken once daily for 12 weeks
|
DU-176b Intermediate Dose 45mg
n=134 participants at risk
DU-176b tablets taken once daily for 12 weeks
|
DU-176b High Dose 60mg
n=130 participants at risk
DU-176b tablets taken once daily for 12 weeks
|
Warfarin
n=125 participants at risk
Warfarin potassium tablets taken once daily for 12 weeks while adjusting dose
|
|---|---|---|---|---|
|
Infections and infestations
nasopharyngitis
|
14.6%
19/130 • Number of events 19
|
18.7%
25/134 • Number of events 27
|
10.8%
14/130 • Number of events 15
|
14.4%
18/125 • Number of events 19
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
5.4%
7/130 • Number of events 7
|
9.7%
13/134 • Number of events 14
|
12.3%
16/130 • Number of events 17
|
4.8%
6/125 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
5.4%
7/130 • Number of events 8
|
4.5%
6/134 • Number of events 7
|
6.2%
8/130 • Number of events 12
|
4.8%
6/125 • Number of events 16
|
|
Investigations
Aspartate aminotransferase increased
|
4.6%
6/130 • Number of events 6
|
6.0%
8/134 • Number of events 8
|
3.1%
4/130 • Number of events 4
|
1.6%
2/125 • Number of events 2
|
|
Investigations
Blood triglycerides increased
|
0.77%
1/130 • Number of events 1
|
3.7%
5/134 • Number of events 5
|
3.8%
5/130 • Number of events 5
|
7.2%
9/125 • Number of events 10
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.4%
7/130 • Number of events 7
|
6.0%
8/134 • Number of events 8
|
5.4%
7/130 • Number of events 7
|
3.2%
4/125 • Number of events 4
|
|
Investigations
glucose urine present
|
3.8%
5/130 • Number of events 6
|
6.7%
9/134 • Number of events 10
|
4.6%
6/130 • Number of events 6
|
5.6%
7/125 • Number of events 8
|
|
Investigations
glood urine present
|
13.1%
17/130 • Number of events 19
|
17.9%
24/134 • Number of events 26
|
23.1%
30/130 • Number of events 33
|
14.4%
18/125 • Number of events 20
|
|
Investigations
protein urine present
|
2.3%
3/130 • Number of events 3
|
4.5%
6/134 • Number of events 6
|
2.3%
3/130 • Number of events 3
|
6.4%
8/125 • Number of events 8
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/130
|
0.75%
1/134 • Number of events 1
|
3.1%
4/130 • Number of events 5
|
0.00%
0/125
|
|
Gastrointestinal disorders
Gingival bleeding
|
3.1%
4/130 • Number of events 6
|
2.2%
3/134 • Number of events 3
|
3.8%
5/130 • Number of events 5
|
4.0%
5/125 • Number of events 5
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
3.1%
4/130 • Number of events 6
|
2.2%
3/134 • Number of events 3
|
3.8%
5/130 • Number of events 5
|
4.0%
5/125 • Number of events 5
|
|
Investigations
Alanine aminotransferase increased
|
3.8%
5/130 • Number of events 5
|
3.7%
5/134 • Number of events 5
|
3.1%
4/130 • Number of events 4
|
0.80%
1/125 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
0.77%
1/130 • Number of events 1
|
1.5%
2/134 • Number of events 2
|
3.1%
4/130 • Number of events 4
|
1.6%
2/125 • Number of events 2
|
|
Investigations
Eosinophil count increased
|
0.77%
1/130 • Number of events 1
|
2.2%
3/134 • Number of events 3
|
3.1%
4/130 • Number of events 4
|
2.4%
3/125 • Number of events 3
|
|
Investigations
Platelet count decreased
|
1.5%
2/130 • Number of events 2
|
3.7%
5/134 • Number of events 5
|
0.00%
0/130
|
0.00%
0/125
|
|
Investigations
Blood alkaline phosphatase increased
|
0.77%
1/130 • Number of events 1
|
3.0%
4/134 • Number of events 4
|
0.00%
0/130
|
1.6%
2/125 • Number of events 2
|
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