Pharmacokinetics and Safety of Vilaprisan in Renal Impairment

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

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.

Study Overview

• Status: Completed
• Conditions: Endometriosis; Uterine Fibroids
• Intervention / Treatment: Drug: Vilaprisan (BAY1002670)

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, Inc.
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects with moderately decreased renal function; 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.	Drug: Vilaprisan (BAY1002670); Single oral dose (1 x 2 mg immediate-release, film-coated tablet)
Experimental: Subjects with severely decreased renal function; Subjects with severe renal impairment not on dialysis with an eGFR <30 mL/min/1.73 m*2 (CKD-EPI formula).	Drug: Vilaprisan (BAY1002670); Single oral dose (1 x 2 mg immediate-release, film-coated tablet)
Experimental: Control subjects with normal renal function; Subjects with an eGFR ≥90 mL/min/1.73 m*2 (CKD-EPI formula) who are matched based on sex, age, race and weight.	Drug: Vilaprisan (BAY1002670); Single oral dose (1 x 2 mg immediate-release, film-coated tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration versus time curve from zero to infinity after single (first) dose (AUC) of BAY1002670	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.	-1hour (h), 30minutes (min), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1day (d), 2d, 3d, 4d, 7d, 10d, 14d
Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of BAY1002670	In subjects with normal and moderately reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	In subjects with normal, moderately, and severely reduced renal function.	Up to 6 weeks
AUC	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
unbound AUC (AUCu)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Cmax	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Unbound Cmax (Cmax,u)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Apparent oral clearance (CL/F)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Unbound CL/F (CLu/F)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Half-life associated with the terminal slope (t1/2)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Renal clearance (CLR)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d
Fraction of free (unbound) drug in plasma (fu)	In subjects with normal, moderately, and severely reduced renal function.	-1h, 30min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h ,16h, 1d, 2d, 3d, 4d, 7d, 10d, 14d

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2018
• Primary Completion (Actual): October 10, 2018
• Study Completion (Actual): February 6, 2019

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (Actual): January 26, 2018

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 1, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Endometriosis; Leiomyoma
• Other Study ID Numbers: 16524

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No