Pharmacokinetics and Safety of Vilaprisan in Renal Impairment

Phase 1

Completed

• Conditions: Uterine Fibroids; Endometriosis
• Interventions: Drug: Vilaprisan (BAY1002670)

• Registration Number: NCT03411980
• Lead Sponsor: Bayer

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.

Study Timeline

• Study First Submitted: 2018-01-22
• Study First Submitted QC: 2018-01-22
• Study First Posted: 2018-01-26
• Study Start: 2018-02-02
• Primary Completion: 2018-10-10
• Study Completion: 2019-02-06
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-01
• Last Update Posted: 2019-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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%.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Subjects with moderately decreased renal function	Vilaprisan (BAY1002670)	Subjects with moderate renal impairment with an estimated glomerular filtration rate (eGFR) of 30 to 59 mL/min/1.73 m\*2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
Subjects with severely decreased renal function	Vilaprisan (BAY1002670)	Subjects with severe renal impairment not on dialysis with an eGFR \<30 mL/min/1.73 m\*2 (CKD-EPI formula).
Control subjects with normal renal function	Vilaprisan (BAY1002670)	Subjects with an eGFR ≥90 mL/min/1.73 m\*2 (CKD-EPI formula) who are matched based on sex, age, race and weight.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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.
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.
Number of participants with adverse events	Up to 6 weeks	In subjects with normal, moderately, and severely reduced renal function.

Trial Locations

Locations (2)

Clinical Pharmacology of Miami, Inc.; 🇺🇸 Miami, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States