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
Overview
- Phase
- Phase 1
- Intervention
- Fulacimstat (BAY1142524)
- Conditions
- Clinical Trial, Phase I
- Sponsor
- Bayer
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Area under the concentration vs. time curve from zero to infinity after single (first) dose (AUC) of BAY1142524
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Normal (healthy subjects)
Healthy subjects matched for age, body weight and gender to the groups with renal impairment
Intervention: Fulacimstat (BAY1142524)
Mildly renal impaired
Subjects with renal impairment and an estimated glomerular function rate between equal or above 60 and below 90 ml/min/1.75 m\*2
Intervention: Fulacimstat (BAY1142524)
Moderately renal impaired
Subjects with renal impairment and an estimated glomerular function rate between equal or above 30 and below 60 ml/min/1.75 m\*2
Intervention: Fulacimstat (BAY1142524)
Severely renal impaired
Subjects with renal impairment and an estimated glomerular function rate between below 30 ml/min/1.75 m\*2
Intervention: Fulacimstat (BAY1142524)
Outcomes
Primary Outcomes
Area under the concentration vs. time curve from zero to infinity after single (first) dose (AUC) of BAY1142524
Time Frame: 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(0-tlast) will be used if mean AUC(tlast ∞) \>20% of AUC)
Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of BAY1142524
Time Frame: 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
Time Frame: 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 (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.
Cmax of unbound drug (Cmax,u) of BAY1142524
Time Frame: 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
An additional blood sample for fu will be collected at 2 hours after dosing.
Secondary Outcomes
- Number of subject with treatment emergent adverse events (TEAEs) as a measure of safety and tolerability(up to 10 days after dosing)