Non-valvular Atrial Fibrillation
Conditions
Keywords
anticoagulant, DU-176b, edoxaban, factor Xa, oral, atrial fibrillation, severe renal impairment
Brief summary
To assess the safety and pharmacokinetics of DU-176b administered to non-valvular atrial fibrillation patients with severe renal impairment, compared with DU-176b administered to non-valvular atrial fibrillation (NVAF) patients with normal renal function or mild renal impairment (Normal/MiRI).
Interventions
DRUGDU-176b 15mg
oral DU-176b 15mg once daily
DRUGDU-176b 30mg
oral DU-176b 30mg once daily
DRUGDU-176b 60mg
oral DU-176b 60mg once daily
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 NVAF and SRI, or patients with NVAF and Normal/MiRI.
Exclusion criteria
* Patients who are on hemodialysis or patients who may start hemodialysis before the follow-up assessment * Patients who are at a significantly high risk for bleeding * Patients who are receiving treatment with any anticoagulant drugs excluding warfarin, rivaroxaban, and dabigatran * Patients who have evidence of hepatic function test abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Any Adjudicated Bleeding Events | 3 months | Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding) |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 50 |
| 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 | 22 |
| 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 | 21 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 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
| Characteristic | SRI 15mg | Total | Normal/MiRI High-dose Group | Normal/MiRI Low-dose Group |
|---|---|---|---|---|
| Age, Continuous | 80.9 years STANDARD_DEVIATION 6.04 | 75.9 years STANDARD_DEVIATION 8.57 | 72.2 years STANDARD_DEVIATION 4.58 | 68.0 years STANDARD_DEVIATION 8.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants | 93 Participants | 21 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 50 participants | 93 participants | 21 participants | 22 participants |
| Sex: Female, Male Female | 22 Participants | 33 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 28 Participants | 60 Participants | 14 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 50 | 14 / 22 | 10 / 21 |
| serious Total, serious adverse events | 5 / 50 | 0 / 22 | 0 / 21 |
Outcome results
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: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SRI 15mg | Incidence of Any Adjudicated Bleeding Events | 20.0 percentage of subjects with bleeds |
| Normal/MiRI Low-dose Group | Incidence of Any Adjudicated Bleeding Events | 22.7 percentage of subjects with bleeds |
| Normal/MiRI High-dose Group | Incidence of Any Adjudicated Bleeding Events | 23.8 percentage of subjects with bleeds |
95% CI: [-14.7, 26.8]Wilcoxon (Mann-Whitney)
95% CI: [-15.4, 25.2]Wilcoxon (Mann-Whitney)