Trial Outcomes & Findings for Safety and Pharmacokinetics Study of DU-176b Administered to Patients With Severe Renal Impairment Undergoing Orthopedic Surgery of The Lower Limbs (NCT NCT01857583)
NCT ID: NCT01857583
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
80 participants
Primary outcome timeframe
14 days
Results posted on
2019-03-05
Participant Flow
Participant milestones
| Measure |
MiRI 30mg DU176b (50 mL/Min ≤ CLCR ≤ 80mL/Min)
Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b
|
SRI 15mg DU176b (15 mL/Min ≤ CLCR < 20 mL/Min)
Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
(15 mL/min ≤ CLCR \< 20 mL/min) 15mg DU-176b
|
SRI 15mg DU176b (20 mL/Min ≤ CLCR < 30 mL/Min)
Severe Renal Impairment group orally administered 15mg DU176b once daily for 14 days.
(20 mL/min ≤ CLCR \< 30 mL/min) 15mg DU-176b
|
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
(20 mL/min ≤ CLCR \< 30mL/min) Fondaparinux
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
30
|
7
|
22
|
21
|
|
Overall Study
Safety Analysis Population
|
30
|
7
|
22
|
20
|
|
Overall Study
COMPLETED
|
29
|
6
|
19
|
17
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
3
|
4
|
Reasons for withdrawal
| Measure |
MiRI 30mg DU176b (50 mL/Min ≤ CLCR ≤ 80mL/Min)
Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b
|
SRI 15mg DU176b (15 mL/Min ≤ CLCR < 20 mL/Min)
Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
(15 mL/min ≤ CLCR \< 20 mL/min) 15mg DU-176b
|
SRI 15mg DU176b (20 mL/Min ≤ CLCR < 30 mL/Min)
Severe Renal Impairment group orally administered 15mg DU176b once daily for 14 days.
(20 mL/min ≤ CLCR \< 30 mL/min) 15mg DU-176b
|
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
(20 mL/min ≤ CLCR \< 30mL/min) Fondaparinux
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
1
|
|
Overall Study
Death
|
0
|
1
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
2
|
Baseline Characteristics
Safety and Pharmacokinetics Study of DU-176b Administered to Patients With Severe Renal Impairment Undergoing Orthopedic Surgery of The Lower Limbs
Baseline characteristics by cohort
| Measure |
MiRI 30mg DU176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min)
n=30 Participants
Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b
|
SRI 15mg DU176b (15 mL/Min ≤ CLCR < 20 mL/Min)
n=7 Participants
Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
(15 mL/min ≤ CLCR \< 20 mL/min) 15mg DU-176b
|
SRI 15mg DU176b (20 mL/Min ≤ CLCR < 30 mL/Min)
n=22 Participants
Severe Renal Impairment group orally administered 15mg DU176b once daily for 14 days.
(20 mL/min ≤ CLCR \< 30 mL/min) 15mg DU-176b
|
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
n=20 Participants
Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
(20 mL/min ≤ CLCR \< 30mL/min)
|
Total
n=79 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
78.1 years
STANDARD_DEVIATION 6.46 • n=5 Participants
|
91.7 years
STANDARD_DEVIATION 7.06 • n=7 Participants
|
86.5 years
STANDARD_DEVIATION 4.31 • n=5 Participants
|
85.7 years
STANDARD_DEVIATION 8.91 • n=4 Participants
|
83.5 years
STANDARD_DEVIATION 8.09 • n=21 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 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
|
30 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
79 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
|
PRIMARY outcome
Timeframe: 14 daysPopulation: The safety analysis set was defined as all subjects who were enrolled in the study, except for those who had significant GCP violations, who had not received the study drug, or who had no safety data after the start of study treatment.
Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding).
Outcome measures
| Measure |
MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min)
n=30 Participants
Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b
|
SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min)
n=7 Participants
Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
(15 mL/min ≤ CLCR \< 20 mL/min) 15mg DU-176b
|
SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min)
n=22 Participants
Severe Renal Impairment group orally administered 15mg DU176b once daily for 14 days.
(20 mL/min ≤ CLCR \< 30 mL/min) 15mg DU-176b
|
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
n=20 Participants
Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
(20 mL/min ≤ CLCR \< 30mL/min)
|
|---|---|---|---|---|
|
Incidence of Any Adjudicated Bleeding Events
|
33.3 percentage of subjects with bleeds
Interval 19.2 to 51.2
|
14.3 percentage of subjects with bleeds
Interval 2.6 to 51.3
|
22.7 percentage of subjects with bleeds
Interval 10.1 to 43.4
|
40.0 percentage of subjects with bleeds
Interval 21.9 to 61.3
|
PRIMARY outcome
Timeframe: 1 monthOutcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 1 monthOutcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 14 daysOutcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 14 daysOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 monthIncidence of adjudicated thromboembolic events (symptomatic Deep Vein Thrombosis (DVT), symptomatic Pulmonary Thromboembolism (PTE), Venous Thromboembolism (VTE) related deaths).
Outcome measures
Outcome data not reported
Adverse Events
MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min)
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min)
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min)
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min)
n=30 participants at risk
Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b
|
SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min)
n=7 participants at risk
Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
(15 mL/min ≤ CLCR \< 20 mL/min) 15mg DU-176b
|
SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min)
n=22 participants at risk
Severe Renal Impairment group orally administered 15mg DU176b once daily for 14 days.
(20 mL/min ≤ CLCR \< 30 mL/min) 15mg DU-176b
|
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
n=20 participants at risk
Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
Fondaparinux (20 mL/min ≤ CLCR \< 30mL/min)
|
|---|---|---|---|---|
|
Cardiac disorders
cardiac failure
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Cardiac disorders
cardiac failure acute
|
0.00%
0/30
|
0.00%
0/7
|
4.5%
1/22 • Number of events 1
|
0.00%
0/20
|
|
Nervous system disorders
dementia
|
0.00%
0/30
|
0.00%
0/7
|
4.5%
1/22 • Number of events 1
|
0.00%
0/20
|
|
Nervous system disorders
cerebral infarction
|
0.00%
0/30
|
0.00%
0/7
|
4.5%
1/22 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
pyelonephritis
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
femur fracture
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
joint dislocation
|
3.3%
1/30 • Number of events 1
|
0.00%
0/7
|
0.00%
0/22
|
0.00%
0/20
|
|
Infections and infestations
sepsis
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Injury, poisoning and procedural complications
periprosthetic fracture
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
Other adverse events
| Measure |
MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min)
n=30 participants at risk
Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b
|
SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min)
n=7 participants at risk
Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
(15 mL/min ≤ CLCR \< 20 mL/min) 15mg DU-176b
|
SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min)
n=22 participants at risk
Severe Renal Impairment group orally administered 15mg DU176b once daily for 14 days.
(20 mL/min ≤ CLCR \< 30 mL/min) 15mg DU-176b
|
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)
n=20 participants at risk
Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
Fondaparinux (20 mL/min ≤ CLCR \< 30mL/min)
|
|---|---|---|---|---|
|
Infections and infestations
cystitis
|
6.7%
2/30 • Number of events 2
|
28.6%
2/7 • Number of events 2
|
13.6%
3/22 • Number of events 3
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/30
|
0.00%
0/7
|
9.1%
2/22 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
6.7%
2/30 • Number of events 2
|
0.00%
0/7
|
4.5%
1/22 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
20.0%
6/30 • Number of events 9
|
0.00%
0/7
|
4.5%
1/22 • Number of events 2
|
15.0%
3/20 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
pubic pain
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Renal and urinary disorders
Haematuria
|
3.3%
1/30 • Number of events 1
|
0.00%
0/7
|
4.5%
1/22 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Impaired healing
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
6.7%
2/30 • Number of events 2
|
14.3%
1/7 • Number of events 1
|
9.1%
2/22 • Number of events 2
|
0.00%
0/20
|
|
Investigations
Aspartate aminotransferase increased
|
3.3%
1/30 • Number of events 1
|
28.6%
2/7 • Number of events 2
|
13.6%
3/22 • Number of events 3
|
0.00%
0/20
|
|
Investigations
Blood bilirubin increased
|
6.7%
2/30 • Number of events 2
|
0.00%
0/7
|
0.00%
0/22
|
0.00%
0/20
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
0.00%
0/20
|
|
Investigations
Blood potassium increased
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Investigations
Fibrin D dimer increased
|
3.3%
1/30 • Number of events 1
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Investigations
Gamma-glutamyltransferase increased
|
16.7%
5/30 • Number of events 5
|
28.6%
2/7 • Number of events 2
|
18.2%
4/22 • Number of events 4
|
0.00%
0/20
|
|
Investigations
Blood urine present
|
13.3%
4/30 • Number of events 4
|
0.00%
0/7
|
9.1%
2/22 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
15.0%
3/20 • Number of events 3
|
|
Infections and infestations
Red blood cells urine positive
|
6.7%
2/30 • Number of events 2
|
0.00%
0/7
|
0.00%
0/22
|
0.00%
0/20
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
22.7%
5/22 • Number of events 5
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/30
|
14.3%
1/7 • Number of events 1
|
0.00%
0/22
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
contusion
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Injury, poisoning and procedural complications
Periprosthetic fracture
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound haematoma
|
0.00%
0/30
|
0.00%
0/7
|
0.00%
0/22
|
5.0%
1/20 • Number of events 1
|
Additional Information
Masayuki Fukuzawa, Associate Director
Daiichi Sankyo.,LTD
Phone: 81-90-5584-2197
Email: [email protected]
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