Trial Outcomes & Findings for DU-176b Phase 2 Dose Finding Study in Subjects With Non-valvular Atrial Fibrillation (NCT NCT00806624)
NCT ID: NCT00806624
Last Updated: 2019-02-26
Results Overview
Incidence of all bleeding (major, clinically relevant non-major and minor) in two fixed dosage of DU-176b in comparison with warfarin as active control in subjects with non-valvular AF.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
234 participants
Primary outcome timeframe
6 months
Results posted on
2019-02-26
Participant Flow
Participant milestones
| Measure |
DU176b 30mg
30 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
DU-176b 60 mg
60 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
Warfarin Potassium
Warfarin was administered once daily at the dose to achieve an INR between 2.0 and 3.0 for 3 months.
|
|---|---|---|---|
|
Overall Study
STARTED
|
79
|
80
|
75
|
|
Overall Study
COMPLETED
|
70
|
68
|
69
|
|
Overall Study
NOT COMPLETED
|
9
|
12
|
6
|
Reasons for withdrawal
| Measure |
DU176b 30mg
30 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
DU-176b 60 mg
60 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
Warfarin Potassium
Warfarin was administered once daily at the dose to achieve an INR between 2.0 and 3.0 for 3 months.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
8
|
0
|
|
Overall Study
Death
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
3
|
3
|
|
Overall Study
discontinued before start of treatment
|
0
|
0
|
1
|
Baseline Characteristics
DU-176b Phase 2 Dose Finding Study in Subjects With Non-valvular Atrial Fibrillation
Baseline characteristics by cohort
| Measure |
DU176b 30mg
n=79 Participants
30 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
DU-176b 60 mg
n=80 Participants
60 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
Warfarin Potassium
n=75 Participants
Warfarin was administered once daily at the dose to achieve an INR between 2.0 and 3.0 for 3 months.
|
Total
n=234 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
64.9 years
STANDARD_DEVIATION 9.12 • n=99 Participants
|
65.9 years
STANDARD_DEVIATION 7.71 • n=107 Participants
|
64.5 years
STANDARD_DEVIATION 9.51 • n=206 Participants
|
65.1 years
STANDARD_DEVIATION 8.78 • n=7 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
81 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=99 Participants
|
55 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
153 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
79 Participants
n=99 Participants
|
80 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
234 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Region of Enrollment
Taiwan
|
35 participants
n=99 Participants
|
35 participants
n=107 Participants
|
34 participants
n=206 Participants
|
104 participants
n=7 Participants
|
|
Region of Enrollment
Singapore
|
5 participants
n=99 Participants
|
4 participants
n=107 Participants
|
4 participants
n=206 Participants
|
13 participants
n=7 Participants
|
|
Region of Enrollment
China
|
7 participants
n=99 Participants
|
8 participants
n=107 Participants
|
7 participants
n=206 Participants
|
22 participants
n=7 Participants
|
|
Region of Enrollment
Korea, Republic of
|
32 participants
n=99 Participants
|
33 participants
n=107 Participants
|
30 participants
n=206 Participants
|
95 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: The Safety Analysis Set was defined as all subjects who received at least one dose of study drug and had at least one post-dose safety assessment. The primary endpoint were analyzed for the subjects who proceeded to the treatment period in the Safety Analysis Set.
Incidence of all bleeding (major, clinically relevant non-major and minor) in two fixed dosage of DU-176b in comparison with warfarin as active control in subjects with non-valvular AF.
Outcome measures
| Measure |
DU176b 30mg
n=79 Participants
30 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
DU-176b 60 mg
n=80 Participants
60 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
Warfarin Potassium
n=75 Participants
Warfarin was administered once daily at the dose to achieve an INR between 2.0 and 3.0 for 3 months.
|
|---|---|---|---|
|
Incidence of All Bleeding
|
20.3 percentage of subjects with bleeds
Interval 12.9 to 30.4
|
23.8 percentage of subjects with bleeds
Interval 15.8 to 34.1
|
29.3 percentage of subjects with bleeds
Interval 20.2 to 40.4
|
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
Adverse Events
DU176b 30mg
Serious events: 3 serious events
Other events: 62 other events
Deaths: 0 deaths
DU-176b 60 mg
Serious events: 10 serious events
Other events: 65 other events
Deaths: 0 deaths
Warfarin Potassium
Serious events: 5 serious events
Other events: 59 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
DU176b 30mg
n=79 participants at risk
30 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
DU-176b 60 mg
n=80 participants at risk
60 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
Warfarin Potassium
n=75 participants at risk
Warfarin was administered once daily at the dose to achieve an INR between 2.0 and 3.0 for 3 months.
|
|---|---|---|---|
|
Cardiac disorders
cardiac failure congestive
|
1.3%
1/79 • Number of events 1
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
|
Cardiac disorders
Coronary artery disease
|
1.3%
1/79 • Number of events 1
|
0.00%
0/80
|
0.00%
0/75
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hydrocele
|
1.3%
1/79 • Number of events 1
|
0.00%
0/80
|
0.00%
0/75
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
0.00%
0/75
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Nervous system disorders
Concussion
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Musculoskeletal and connective tissue disorders
Back injury
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Musculoskeletal and connective tissue disorders
Neck injury
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Blood and lymphatic system disorders
Gingival bleeding
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/79
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
|
Cardiac disorders
Hypertensive crisis
|
0.00%
0/79
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/79
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/79
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
Other adverse events
| Measure |
DU176b 30mg
n=79 participants at risk
30 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
DU-176b 60 mg
n=80 participants at risk
60 mg of DU-176b was administered once daily in the morning in principle for 3 months.
|
Warfarin Potassium
n=75 participants at risk
Warfarin was administered once daily at the dose to achieve an INR between 2.0 and 3.0 for 3 months.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/79
|
1.2%
1/80 • Number of events 1
|
6.7%
5/75 • Number of events 5
|
|
Gastrointestinal disorders
Gingival bleeding
|
5.1%
4/79 • Number of events 4
|
7.5%
6/80 • Number of events 6
|
0.00%
0/75
|
|
General disorders
Chest discomfort
|
5.1%
4/79 • Number of events 4
|
2.5%
2/80 • Number of events 2
|
4.0%
3/75 • Number of events 3
|
|
General disorders
Oedema peripheral
|
1.3%
1/79 • Number of events 1
|
5.0%
4/80 • Number of events 4
|
2.7%
2/75 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
1.3%
1/79 • Number of events 1
|
5.0%
4/80 • Number of events 4
|
1.3%
1/75 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
1.3%
1/79 • Number of events 1
|
7.5%
6/80 • Number of events 6
|
6.7%
5/75 • Number of events 5
|
|
Investigations
Alanine aminotransferase increased
|
7.6%
6/79 • Number of events 6
|
1.2%
1/80 • Number of events 1
|
1.3%
1/75 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
6.3%
5/79 • Number of events 5
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Investigations
Blood urine present
|
11.4%
9/79 • Number of events 9
|
15.0%
12/80 • Number of events 12
|
9.3%
7/75 • Number of events 7
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
6.3%
5/79 • Number of events 5
|
2.5%
2/80 • Number of events 2
|
0.00%
0/75
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
7.6%
6/79 • Number of events 6
|
5.0%
4/80 • Number of events 4
|
1.3%
1/75 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.3%
1/79 • Number of events 1
|
5.0%
4/80 • Number of events 4
|
1.3%
1/75 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
8.9%
7/79 • Number of events 7
|
10.0%
8/80 • Number of events 8
|
1.3%
1/75 • Number of events 1
|
|
Nervous system disorders
Headache
|
6.3%
5/79 • Number of events 5
|
7.5%
6/80 • Number of events 6
|
2.7%
2/75 • Number of events 2
|
|
Renal and urinary disorders
Haematuria
|
11.4%
9/79 • Number of events 9
|
12.5%
10/80 • Number of events 10
|
18.7%
14/75 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.3%
5/79 • Number of events 5
|
3.8%
3/80 • Number of events 3
|
6.7%
5/75 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.1%
4/79 • Number of events 4
|
0.00%
0/80
|
0.00%
0/75
|
|
Blood and lymphatic system disorders
Anaemia
|
2.5%
2/79 • Number of events 2
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
|
Cardiac disorders
Angina pectoris
|
2.5%
2/79 • Number of events 2
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
2.7%
2/75 • Number of events 2
|
|
Cardiac disorders
Palpitations
|
1.3%
1/79 • Number of events 1
|
3.8%
3/80 • Number of events 3
|
0.00%
0/75
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/79
|
0.00%
0/80
|
2.7%
2/75 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.5%
2/79 • Number of events 2
|
2.5%
2/80 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
2.5%
2/79 • Number of events 2
|
3.8%
3/80 • Number of events 3
|
1.3%
1/75 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/79
|
0.00%
0/80
|
2.7%
2/75 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.3%
1/79 • Number of events 1
|
2.5%
2/80 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
3.8%
3/79 • Number of events 3
|
3.8%
3/80 • Number of events 3
|
4.0%
3/75 • Number of events 3
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
|
Gastrointestinal disorders
nausea
|
2.5%
2/79 • Number of events 2
|
3.8%
3/80 • Number of events 3
|
0.00%
0/75
|
|
Gastrointestinal disorders
peptic ulcer
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
2.7%
2/75 • Number of events 2
|
|
Gastrointestinal disorders
periodontitis
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
|
Gastrointestinal disorders
toothache
|
0.00%
0/79
|
3.8%
3/80 • Number of events 3
|
0.00%
0/75
|
|
General disorders
chest pain
|
3.8%
3/79 • Number of events 3
|
1.2%
1/80 • Number of events 1
|
1.3%
1/75 • Number of events 1
|
|
General disorders
fatigue
|
1.3%
1/79 • Number of events 1
|
1.2%
1/80 • Number of events 1
|
2.7%
2/75 • Number of events 2
|
|
Infections and infestations
influenza
|
3.8%
3/79 • Number of events 3
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Injury, poisoning and procedural complications
contusion
|
1.3%
1/79 • Number of events 1
|
2.5%
2/80 • Number of events 2
|
2.7%
2/75 • Number of events 2
|
|
Investigations
Blood urea increased
|
2.5%
2/79 • Number of events 2
|
0.00%
0/80
|
0.00%
0/75
|
|
Investigations
Blood uric acid increased
|
2.5%
2/79 • Number of events 2
|
0.00%
0/80
|
1.3%
1/75 • Number of events 1
|
|
Investigations
Glucose tolerance test abnormal
|
1.3%
1/79 • Number of events 1
|
2.5%
2/80 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
|
Investigations
Hypertriglyceridaemia
|
1.3%
1/79 • Number of events 1
|
0.00%
0/80
|
2.7%
2/75 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
2.5%
2/79 • Number of events 2
|
0.00%
0/80
|
0.00%
0/75
|
|
Musculoskeletal and connective tissue disorders
myositis
|
2.5%
2/79 • Number of events 2
|
0.00%
0/80
|
0.00%
0/75
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
2.7%
2/75 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
0.00%
0/75
|
|
Nervous system disorders
Somnolence
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
0.00%
0/75
|
|
Psychiatric disorders
Insomnia
|
2.5%
2/79 • Number of events 2
|
1.2%
1/80 • Number of events 1
|
0.00%
0/75
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
1/79 • Number of events 1
|
2.5%
2/80 • Number of events 2
|
2.7%
2/75 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.5%
2/79 • Number of events 2
|
1.2%
1/80 • Number of events 1
|
4.0%
3/75 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
0.00%
0/75
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
2.7%
2/75 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
rash
|
0.00%
0/79
|
0.00%
0/80
|
2.7%
2/75 • Number of events 2
|
|
Vascular disorders
flushing
|
0.00%
0/79
|
2.5%
2/80 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Korea study sites agree that any results of the study are not to be published individually or collectively in whole or part by study site, its employees or agents until after the coordinated multicenter publication or one year after the termination of the study, whichever occurs fist.
- Publication restrictions are in place
Restriction type: OTHER