Uterine Fibroids, Endometriosis
Conditions
Keywords
Pharmacokinetics
Brief summary
The purpose of the study is to evaluate the pharmacokinetics of vilaprisan in subjects with moderate to severe renal impairment compared with matched subjects with normal renal function.
Detailed description
This is a multiple-center, open-label, non-randomized, single-dose study in 3 parallel groups of subjects with moderately or severely impaired renal function or normal renal function matched with regard to sex, age, race and weight. PK blood and urine sampling for determination of vilaprisan concentrations in plasma and urine, respectively, will be preformed at pre-defined time points up to 14 days post-dose. Safety and tolerability will be assessed through adverse events, clinical laboratory tests, vital signs, 12-lead electrocardiograms and physical examinations.
Interventions
Single oral dose (1 x 2 mg immediate-release, film-coated tablet)
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI: 18 to 40 kg/m\*2 (inclusive) * Decreased renal function, as assessed at screening, based on serum creatinine and calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, either: Moderately impaired renal function: eGFR: 30 to 59 mL/min/1.73 m\*2; or Severely impaired renal function: eGFR \<30 mL/min/1.73 m\*2 but not on dialysis \- Normal renal function, as assessed at screening and based on serum creatinine according to the CKD-EPI formula: eGFR ≥90 mL/min/1.73 m\*2
Exclusion criteria
* Any relevant disease within 4 weeks prior to study drug administration including infections and acute gastrointestinal diseases (vomiting, diarrhea, constipation) requiring medical treatment. * Severe cerebrovascular or cardiac disorders less than 6 months prior to study drug administration, e.g. stroke, myocardial infarction, unstable angina pectoris, percutaneous transluminal coronary angioplasty or coronary artery bypass graft, congestive heart failure of Grade III or IV according to New York Heart Association, or arrhythmia requiring antiarrhythmic treatment. * Malignancy diagnosed or treated within the past 5 years. This does not include adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin. * Acute renal failure or acute nephritis within the past 2 years. * Pregnancy or lactation. * Use of CYP3A4 inducers from 2 weeks before study drug administration until last day of blood sampling for PK after study drug administration, including grapefruits. * Insufficiently controlled diabetes mellitus with fasting blood glucose \>220 mg/dL or HbA1c \>10%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration versus time curve from zero to infinity after single (first) dose (AUC) of BAY1002670 | -1hour (h), 30minutes (min), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1day (d), 2d, 3d, 4d, 7d, 10d, 14d | Area under the concentration versus time curve from zero to the last data point above the lower limit of quantitation \[AUC(0-tlast)\], if AUC cannot be estimated in all subjects. In subjects with normal and moderately reduced renal function. |
| Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of BAY1002670 | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal and moderately reduced renal function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| unbound AUC (AUCu) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Cmax | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Unbound Cmax (Cmax,u) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Apparent oral clearance (CL/F) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Number of participants with adverse events | Up to 6 weeks | In subjects with normal, moderately, and severely reduced renal function. |
| Half-life associated with the terminal slope (t1/2) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Renal clearance (CLR) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Fraction of free (unbound) drug in plasma (fu) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| Unbound CL/F (CLu/F) | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
| AUC | -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d | In subjects with normal, moderately, and severely reduced renal function. |
Countries
United States
Outcome results
None listed