Venous Thromboembolism
Conditions
Keywords
anticoagulant, DU-176b, edoxaban, factor Xa, oral, orthopedic surgery of lower limbs, severe renal impairment
Brief summary
To assess the safety and pharmacokinetics of DU-176b administered to patients with severe renal impairment undergoing orthopedic surgery of the lower limbs, compared with DU-176b administered to patients with mild renal impairment (MiRI) undergoing orthopedic surgery of the lower limbs. For reference, the safety of DU-176b in patients with SRI undergoing orthopedic surgery of the lower limbs will be compared with that of fondaparinux.
Interventions
DRUG15mg DU-176b
DRUG30mg DU-176b
DRUGFondaparinux
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with SRI or MiRI undergoing orthopedic surgery of the lower limbs
Exclusion criteria
* Patients who are on hemodialysis or are scheduled to undergo hemodialysis during the study period * Patients who are at a significantly high risk for bleeding or thromboembolism * Patients who are receiving another antithrombotic therapy and are unable to suspend the therapy * Patients who have evidence of hepatic function test abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Any Adjudicated Bleeding Events | 14 days | Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding). |
| Incidence of Adverse Events | 1 month | — |
| Incidence of Adverse Drug Reactions | 1 month | — |
| Plasma Concentration of DU-176b | 14 days | — |
| Plasma Concentration of D21-2393 | 14 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adjudicated Thromboembolic Events | 1 month | Incidence of adjudicated thromboembolic events (symptomatic Deep Vein Thrombosis (DVT), symptomatic Pulmonary Thromboembolism (PTE), Venous Thromboembolism (VTE) related deaths). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MiRI 30mg DU176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min) Mild Renal Impairment group orally administered 30mg DU176b once daily for 14 days.
(50 mL/min ≤ CLCR ≤ 80 mL/min) 30mg DU-176b | 30 |
| 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 | 7 |
| 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 | 22 |
| 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) | 20 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 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
| Characteristic | MiRI 30mg DU176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min) | Total | Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min) | SRI 15mg DU176b (20 mL/Min ≤ CLCR < 30 mL/Min) | SRI 15mg DU176b (15 mL/Min ≤ CLCR < 20 mL/Min) |
|---|---|---|---|---|---|
| Age, Continuous | 78.1 years STANDARD_DEVIATION 6.46 | 83.5 years STANDARD_DEVIATION 8.09 | 85.7 years STANDARD_DEVIATION 8.91 | 86.5 years STANDARD_DEVIATION 4.31 | 91.7 years STANDARD_DEVIATION 7.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 79 Participants | 20 Participants | 22 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 27 Participants | 72 Participants | 20 Participants | 19 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 0 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 30 | 6 / 7 | 12 / 22 | 12 / 20 |
| serious Total, serious adverse events | 1 / 30 | 3 / 7 | 2 / 22 | 3 / 20 |
Outcome results
Primary
Incidence of Adverse Drug Reactions
Time frame: 1 month
Primary
Incidence of Adverse Events
Time frame: 1 month
Primary
Incidence of Any Adjudicated Bleeding Events
Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding).
Time frame: 14 days
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min) | Incidence of Any Adjudicated Bleeding Events | 33.3 percentage of subjects with bleeds |
| SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min) | Incidence of Any Adjudicated Bleeding Events | 14.3 percentage of subjects with bleeds |
| SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min) | Incidence of Any Adjudicated Bleeding Events | 22.7 percentage of subjects with bleeds |
| Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min) | Incidence of Any Adjudicated Bleeding Events | 40.0 percentage of subjects with bleeds |
95% CI: [-10, 33.6]ANCOVA
95% CI: [-10.2, 42.1]ANCOVA
Primary
Plasma Concentration of D21-2393
Time frame: 14 days
Primary
Plasma Concentration of DU-176b
Time frame: 14 days
Secondary
Incidence of Adjudicated Thromboembolic Events
Incidence of adjudicated thromboembolic events (symptomatic Deep Vein Thrombosis (DVT), symptomatic Pulmonary Thromboembolism (PTE), Venous Thromboembolism (VTE) related deaths).
Time frame: 1 month