Renal Impairment Study

Study Overview
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Brief Summary
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The study will investigate the pharmacokinetics of BAY1142524 in subjects with mild to severe renal impairment compared to age; weight, and gender-matched healthy subjects.

Official Title
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Investigation of Pharmacokinetics, Safety, and Tolerability of a Single Oral 25 mg BAY 1142524 IR Tablet Dose in Male and Female Subjects With Renal Impairment and in Age-, Gender-, and Weight-matched Healthy Subjects in a Single Center, Non-controlled, Open-label, Observational Design

Conditions
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Clinical Trial, Phase I

Intervention / Treatment
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* Drug: Fulacimstat (BAY1142524)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI): 18 to 34 kg/m² (both inclusive) Men or confirmed postmenopausal women (by medical report verification and defined as exhibiting natural amenorrhea for at least 12 months before screening or as exhibiting natural amenorrhea for at least 6 months before screening with documented serum follicle-stimulating hormone levels >40 mIU/mL, provided that no prior hormonal treatment has taken place) or women without childbearing potential based on surgical treatment at least 6 weeks before screening such as bilateral tubal ligation, bilateral oophorectomy or hysterectomy (documented by medical report verification). Subjects with renal impairment: eGFR <90 mL/min/1.73 m*2 determined from serum creatinine 2 -10 days prior to dosing. Stable renal disease, i.e. a serum creatinine value determined at least 3 months before the pre-study visit (e.g. during routine diagnostics) should not vary by more than 20% from the serum creatinine value determined at the pre-study visit - Healthy subjects eGFR ≥90 mL/min/1.73 m*2 determined from serum creatinine 2 -10 days prior to dosing. Needs to be within the required age and body weight range of Group 1 (which should not vary by more than+- 10 years and +-10 kg to Groups 2-4). Exclusion Criteria: Clinically relevant findings(e.g. blood pressure, electrocardiogram, ECG; physical examination,laboratory examination) Relevant impairment in liver function. Pre-existing diseases (including impairment of liver function) for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal. Any organ transplant < 1 year before participation in this study. Subject under dialysis or planned to start dialysis during participation in the study. Failure of any other major organ system other than the kidney.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal (healthy subjects)<br>Healthy subjects matched for age, body weight and gender to the groups with renal impairment | Drug: Fulacimstat (BAY1142524)<br>* single oral dose of 25 mg immediate-release tablet BAY1142524<br>|
| Experimental: Mildly renal impaired<br>Subjects with renal impairment and an estimated glomerular function rate between equal or above 60 and below 90 ml/min/1.75 m*2 | Drug: Fulacimstat (BAY1142524)<br>* single oral dose of 25 mg immediate-release tablet BAY1142524<br>|
| Experimental: Moderately renal impaired<br>Subjects with renal impairment and an estimated glomerular function rate between equal or above 30 and below 60 ml/min/1.75 m*2 | Drug: Fulacimstat (BAY1142524)<br>* single oral dose of 25 mg immediate-release tablet BAY1142524<br>|
| Experimental: Severely renal impaired<br>Subjects with renal impairment and an estimated glomerular function rate between below 30 ml/min/1.75 m*2 | Drug: Fulacimstat (BAY1142524)<br>* single oral dose of 25 mg immediate-release tablet BAY1142524<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration vs. time curve from zero to infinity after single (first) dose (AUC) of BAY1142524 | AUC(0-tlast) will be used if mean AUC(tlast ∞) >20% of AUC) | Pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,15,24,36,48,96hours post dose | 
| Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of BAY1142524 |  | Pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,15,24,36,48,96hours post dose | 
| AUC of unbound drug (AUCu) of BAY1142524 | AUC (0-tlast) u will be used if mean AUC (tlast ∞) >20% of AUC). An additional blood sample for fu will be collected at 2 hours after dosing. | Pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,15,24,36,48,96hours post dose | 
| Cmax of unbound drug (Cmax,u) of BAY1142524 | An additional blood sample for fu will be collected at 2 hours after dosing. | Pre-dose,0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,15,24,36,48,96hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subject with treatment emergent adverse events (TEAEs) as a measure of safety and tolerability |  | up to 10 days after dosing |