Trial Outcomes & Findings for Safety and Pharmacokinetics Study of DU-176b Administered to Non-valvular Atrial Fibrillation With Severe Renal Impairment (NCT NCT01857622)
NCT ID: NCT01857622
Last Updated: 2019-03-05
Results Overview
Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
93 participants
Primary outcome timeframe
3 months
Results posted on
2019-03-05
Participant Flow
Participant milestones
| Measure |
SRI 15mg
Severe Renal Impairment DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.
DU-176b 15mg: oral DU-176b 15mg once daily
|
Normal/MiRI Low-dose Group
Normal or Mild Renal impairment DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 30mg: oral DU-176b 30mg once daily
|
Normal/MiRI High-dose Group
Normal or Mild Renal Impairment DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 60mg: oral DU-176b 60mg once daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
50
|
22
|
21
|
|
Overall Study
COMPLETED
|
39
|
21
|
19
|
|
Overall Study
NOT COMPLETED
|
11
|
1
|
2
|
Reasons for withdrawal
| Measure |
SRI 15mg
Severe Renal Impairment DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.
DU-176b 15mg: oral DU-176b 15mg once daily
|
Normal/MiRI Low-dose Group
Normal or Mild Renal impairment DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 30mg: oral DU-176b 30mg once daily
|
Normal/MiRI High-dose Group
Normal or Mild Renal Impairment DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 60mg: oral DU-176b 60mg once daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
5
|
0
|
2
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
4
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
Safety and Pharmacokinetics Study of DU-176b Administered to Non-valvular Atrial Fibrillation With Severe Renal Impairment
Baseline characteristics by cohort
| Measure |
SRI 15mg
n=50 Participants
Severe Renal Impairment DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.
DU-176b 15mg: oral DU-176b 15mg once daily
|
Normal/MiRI Low-dose Group
n=22 Participants
Normal or Mild Renal impairment DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 30mg: oral DU-176b 30mg once daily
|
Normal/MiRI High-dose Group
n=21 Participants
Normal or Mild Renal Impairment DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 60mg: oral DU-176b 60mg once daily
|
Total
n=93 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
80.9 years
STANDARD_DEVIATION 6.04 • n=5 Participants
|
68.0 years
STANDARD_DEVIATION 8.91 • n=7 Participants
|
72.2 years
STANDARD_DEVIATION 4.58 • n=5 Participants
|
75.9 years
STANDARD_DEVIATION 8.57 • n=4 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
60 Participants
n=4 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
|
|
Race (NIH/OMB)
Asian
|
50 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
93 Participants
n=4 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
|
|
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
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
|
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
|
|
Region of Enrollment
Japan
|
50 participants
n=5 Participants
|
22 participants
n=7 Participants
|
21 participants
n=5 Participants
|
93 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 3 monthsIncidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding)
Outcome measures
| Measure |
SRI 15mg
n=50 Participants
Severe Renal Impairment DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.
DU-176b 15mg: oral DU-176b 15mg once daily
|
Normal/MiRI Low-dose Group
n=22 Participants
Normal or Mild Renal impairment DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 30mg: oral DU-176b 30mg once daily
|
Normal/MiRI High-dose Group
n=21 Participants
Normal or Mild Renal Impairment DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 60mg: oral DU-176b 60mg once daily
|
|---|---|---|---|
|
Incidence of Any Adjudicated Bleeding Events
|
20.0 percentage of subjects with bleeds
Interval 11.2 to 33.0
|
22.7 percentage of subjects with bleeds
Interval 10.1 to 43.4
|
23.8 percentage of subjects with bleeds
Interval 10.6 to 45.1
|
Adverse Events
SRI 15mg
Serious events: 5 serious events
Other events: 33 other events
Deaths: 0 deaths
Normal/MiRI Low-dose Group
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Normal/MiRI High-dose Group
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SRI 15mg
n=50 participants at risk
Severe Renal Impairment DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.
DU-176b 15mg: oral DU-176b 15mg once daily
|
Normal/MiRI Low-dose Group
n=22 participants at risk
Normal or Mild Renal impairment DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 30mg: oral DU-176b 30mg once daily
|
Normal/MiRI High-dose Group
n=21 participants at risk
Normal or Mild Renal Impairment DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 60mg: oral DU-176b 60mg once daily
|
|---|---|---|---|
|
Infections and infestations
pneumonia
|
6.0%
3/50 • Number of events 3
|
0.00%
0/22
|
0.00%
0/21
|
|
Cardiac disorders
cardiac failure
|
2.0%
1/50 • Number of events 1
|
0.00%
0/22
|
0.00%
0/21
|
|
Cardiac disorders
cardiac failure congestive
|
2.0%
1/50 • Number of events 1
|
0.00%
0/22
|
0.00%
0/21
|
|
Cardiac disorders
ventricular tachycardia
|
2.0%
1/50 • Number of events 1
|
0.00%
0/22
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
pleurisy
|
2.0%
1/50 • Number of events 1
|
0.00%
0/22
|
0.00%
0/21
|
Other adverse events
| Measure |
SRI 15mg
n=50 participants at risk
Severe Renal Impairment DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.
DU-176b 15mg: oral DU-176b 15mg once daily
|
Normal/MiRI Low-dose Group
n=22 participants at risk
Normal or Mild Renal impairment DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 30mg: oral DU-176b 30mg once daily
|
Normal/MiRI High-dose Group
n=21 participants at risk
Normal or Mild Renal Impairment DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.
DU-176b 60mg: oral DU-176b 60mg once daily
|
|---|---|---|---|
|
Infections and infestations
nasopharyngitis
|
10.0%
5/50 • Number of events 5
|
18.2%
4/22 • Number of events 4
|
23.8%
5/21 • Number of events 5
|
|
Infections and infestations
pneumonia
|
6.0%
3/50 • Number of events 3
|
0.00%
0/22
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
6.0%
3/50 • Number of events 3
|
0.00%
0/22
|
0.00%
0/21
|
|
Gastrointestinal disorders
gingival bleeding
|
2.0%
1/50 • Number of events 1
|
9.1%
2/22 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
8.0%
4/50 • Number of events 5
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Renal and urinary disorders
haematuria
|
6.0%
3/50 • Number of events 3
|
0.00%
0/22
|
19.0%
4/21 • Number of events 4
|
|
Investigations
Blood creatinine increased
|
8.0%
4/50 • Number of events 4
|
0.00%
0/22
|
0.00%
0/21
|
|
Investigations
occult blood
|
6.0%
3/50 • Number of events 3
|
0.00%
0/22
|
0.00%
0/21
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Metabolism and nutrition disorders
gout
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Metabolism and nutrition disorders
Decreased appetit
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Cardiac disorders
Ventricular tachycardia
|
4.0%
2/50 • Number of events 2
|
0.00%
0/22
|
0.00%
0/21
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
rash
|
4.0%
2/50 • Number of events 2
|
0.00%
0/22
|
0.00%
0/21
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
General disorders
chest pain
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Investigations
Blood urea increased
|
4.0%
2/50 • Number of events 2
|
0.00%
0/22
|
0.00%
0/21
|
|
Investigations
Electrocardiogram QT prolonged
|
2.0%
1/50 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Investigations
Intraocular pressure increased
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
gingivitis
|
0.00%
0/50
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal pain
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
|
Investigations
blood bilirubin increased
|
0.00%
0/50
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
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