Renal Insufficiency, Chronic
Conditions
Brief summary
The study to be conducted is a prospective, open label trial. It is designed to evaluate the pharmacokinetic/pharmacodynamic and coagulation parameters and safety of dabigatran etexilate in patients with chronic kidney disease.
Interventions
DRUGDabigatran Etexilate
Dabigatran Etexilate 75mg twice daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients aged 18 years and older 2. Impaired renal function defined as a stable Cockcroft-Gault and/or actual creatinine clearance between 15-30 ml/min over the last 3 months before study participation. 3. The single use of either aspirin or Vitamin K Antagonists 4. Provision of informed consent.
Exclusion criteria
1. Unstable renal function and Creatinin Clearance \<15mL/min 2. Patients treated with two or more platelet aggregation inhibitors 3. Use of or indication for therapeutic heparin 4. Patients with prosthetic heart valves 5. Haemorrhagic disorder or bleeding diathesis 6. Platelet count \<100 109/L) at screening or during the last 30 days before screening. 7. Participation in another drug trial in the last 30 days before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,ss | -0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h | Maximum concentration of Dabigatran etexilate in plasma at steady state was measured. The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration. |
| AUCtau,ss | -0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h | Area under the plasma concentration-time curve of the total dabigatran at steady state over a uniform dosing interval tau was measured. The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran 75 mg Oral administration of 1 capsule of Dabigatran etexilate 75 mg twice daily | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated | 3 |
Baseline characteristics
| Characteristic | Dabigatran 75 mg |
|---|---|
| Age, Continuous | 72.7 years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
AUCtau,ss
Area under the plasma concentration-time curve of the total dabigatran at steady state over a uniform dosing interval tau was measured. The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.
Time frame: -0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran 75 mg | AUCtau,ss | 2140 ng*h/mL | Geometric Coefficient of Variation 51.9 |
Comparison: Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median GFR, 2: \> median GFR).~Median is calculated based on trial data of treated setp-value: 0.4692ANOVA
Comparison: Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median age, 2: \> median age).~Median is calculated based on trial data of treated setp-value: 0.9734ANOVA
Comparison: Patients were classified based on the gender distribution.p-value: 0.9201ANOVA
Primary
Cmax,ss
Maximum concentration of Dabigatran etexilate in plasma at steady state was measured. The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.
Time frame: -0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h
Population: Pharmacokinetic set (PKS) which included all treated subjects that provided at least 1 observation for at least 1 primary pharmacokinetic endpoint without important protocol violations with respect to the evaluation of the pharmacokinetic endpoints and with predose values not greater than 5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran 75 mg | Cmax,ss | 207 ng/mL | Geometric Coefficient of Variation 53.9 |
Comparison: Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median GFR (Glomerular filtration rate), 2: \> median GFR).~Median is calculated based on trial data of treated setp-value: 0.5186ANOVA
Comparison: Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median age, 2: \> median age).~Median is calculated based on trial data of treated setp-value: 0.9883ANOVA
Comparison: Patients were classified based on the gender distribution.p-value: 0.7853ANOVA