Atrial Fibrillation
Conditions
Brief summary
The goal of this study is to assess dabigatran pharmacokinetics in NVAF subjects with severe renal impairment defined as creatinine clearance between 15 and 30 mL/min calculated by Cockcroft-Gault formula. The dabigatran etexilate dose of 75 mg BID was approved by the FDA for NVAF patients with severe renal impairment (CrCl 15-30 mL/min) , based on pharmacokinetic modeling and simulation.
Interventions
DRUGPradaxa, dabigatran etexilate
75mg BID by oral
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed with non-valvular atrial fibrillation with an indication for the anticoagulation therapy, * Subjects with severe renal function impairment defined as creatinine clearance between 15 and 30 mL/min by Cockcroft-Gault formula, * Male and female patients, age =18 years at entry
Exclusion criteria
* Contraindications to Pradaxa (history of a serious hypersensitivity reaction to Pradaxa, active pathological bleeding, patients with mechanical prosthetic heart valve), * Creatinine clearance \<15ml/min or patients with End Stage Renal Disease on dialysis, * Creatinine clearance \>30 ml/min, * Pre-menopausal women (last menstruation less than one year prior to informed consent) who are nursing or pregnant, or are of child bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study. Acceptable methods of birth control include abstinence, tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, double barrier method and vasectomised partner, * Patients who are participating in another drug study, * Patients who have participated in another drug study within 6 weeks, * Patients considered unreliable by the investigator concerning the requirements for participating in the study, including a follow-up interview, * Any condition the investigator believes would not allow safe participation in the study,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-dose Concentration of the Analyte in Plasma at Steady State Immediately Before Administration of the Next Dose | Immediately before the last drug administration, on day 8 | Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss) taken at approximately 12 hours after the last dose (trough). |
| Concentration of Analyte in Plasma at Steady State at 2 Hours After Administration of the Last Dose | 2 hours after the last drug administration, on day 8 | Concentration of analyte in plasma at steady state at 2 hours after administration of the last dose (C2,ss) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Etexilate Dabigatran etexilate 75mg capsule administered orally, twice daily (BID), for at least 7 days. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Died in post treatment phase | 1 |
Baseline characteristics
| Characteristic | Dabigatran Etexilate |
|---|---|
| Age, Continuous | 83.35 Years STANDARD_DEVIATION 7.55 |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 60 |
| serious Total, serious adverse events | 2 / 60 |
Outcome results
Primary
Concentration of Analyte in Plasma at Steady State at 2 Hours After Administration of the Last Dose
Concentration of analyte in plasma at steady state at 2 hours after administration of the last dose (C2,ss)
Time frame: 2 hours after the last drug administration, on day 8
Population: PKS. Analysis includes patients with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Concentration of Analyte in Plasma at Steady State at 2 Hours After Administration of the Last Dose | 202 ng/mL | Geometric Coefficient of Variation 70.6 |
Primary
Pre-dose Concentration of the Analyte in Plasma at Steady State Immediately Before Administration of the Next Dose
Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss) taken at approximately 12 hours after the last dose (trough).
Time frame: Immediately before the last drug administration, on day 8
Population: Pharmacokinetic (PK) set (PKS) which included all patients in the treated set with analyzable data in at least one observation for at least one primary endpoint without important protocol violations relevant to the evaluation of PK. Analysis includes patients with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Pre-dose Concentration of the Analyte in Plasma at Steady State Immediately Before Administration of the Next Dose | 155 ng/mL | Geometric Coefficient of Variation 76.9 |