Clinical trial NCT03411980: Pharmacokinetics and Safety of Vilaprisan in Renal Impairment
Official title: An Open-label, Single-dose Study to Evaluate the Pharmacokinetics and Safety of Vilaprisan in Subjects With Decreased Renal Function in Comparison With Matched Subjects With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Uterine Fibroids
Endometriosis
Keywords: Pharmacokinetics
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-01-26
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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%.

Primary outcomes:
measure: Area under the concentration versus time curve from zero to infinity after single (first) dose (AUC) of BAY1002670
timeFrame: -1hour (h), 30minutes (min), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1day (d), 2d, 3d, 4d, 7d, 10d, 14d
measure: Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of BAY1002670
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 6 weeks
measure: AUC
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: unbound AUC (AUCu)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Cmax
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Unbound Cmax (Cmax,u)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Apparent oral clearance (CL/F)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Unbound CL/F (CLu/F)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Half-life associated with the terminal slope (t1/2)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Renal clearance (CLR)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
measure: Fraction of free (unbound) drug in plasma (fu)
timeFrame: -1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
References: