This is a Phase 1 study to evaluate the pharmacokinetics (PK), safety and tolerability of epetraborole tablets in adult subjects with normal renal function, subjects with various degrees of renal impairment, and subjects with end-stage renal disease (ESRD) receiving intermittent hemodialysis (IHD) therapy.
This is a multicenter, open-label, non-randomized, parallel group study in which a total of 40 subjects will be enrolled in one of 5 cohorts (8 subjects per cohort). Subjects will be enrolled based on their estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. * Cohort 1: Normal renal function (eGFR ≥ 90 mL/min/1.73 m2) * Cohort 2: Mild renal impairment (eGFR ≥ 60 and \< 90 mL/min/1.73 m2) * Cohort 3: Moderate renal impairment (eGFR ≥ 30 and \< 60 mL/min/1.73 m2) * Cohort 4: Severe renal impairment (eGFR \< 30 mL/min/1.73 m2) * Cohort 5: ESRD (eGFR \< 15 mL/min/1.73 m2) receiving IHD. Subjects must be stable and receiving IHD at least 3 times a week for at least 3 months prior to Screening.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
40
Epetraborole hydrochloride 250 mg tablets for oral administration
Advanced Pharma CR
Miami, Florida, United States
Orlando Clinical Research Center
Orlando, Florida, United States
Nucleus Network
Saint Paul, Minnesota, United States
Characterize the PK Profile of Epetraborole and M3: Maximum Plasma Concentration
Determination of the maximum observed plasma concentration (Cmax)
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3: Area Under the Plasma Concentration Versus Time Curve from Time 0 to the Last Time Point Evaluated
Determine the area under the plasma concentration versus time curve from time 0 to the last time point evaluated (AUC0-t)
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3: Area Under the Plasma Concentration Versus Time Curve from Time 0 to 24 hours
Determine the area under the plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3: Area Under the Plasma Concentration Versus Time Curve from Time 0 to Infinity
Determine area under the drug concentration versus time curve, from time zero to infinity (AUC0-∞)
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3: Apparent total plasma clearance of drug
Determine the apparent total plasma clearance of drug (CL/F)
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3: Time to Maximum Plasma Concentration
Determination the time to maximum plasma concentration (Tmax)
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Characterize the PK Profile of Epetraborole: Plasma from Hemodialysis Flow
Determine the AUC from 0 to the last quantifiable concentration AUClast immediately after the end of dialysis period from inflow (arterial) line
Time frame: Cohort 5: Day 5
Characterize the PK Profile of Epetraborole:Plasma from Hemodialysis Flow
Determine the AUC from 0 to the last quantifiable concentration AUClast immediately after the end of dialysis period from inflow (venous) line
Time frame: Cohort 5: Day 5
Characterize the PK Profile of Epetraborole and M3 in Urine: Cumulative drug excreted in urine over time
Determine the cumulative amount excreted over all time intervals (0 to T), calculated as the sum of all amounts excreted from each interval (t1-t2)
Time frame: Cohorts 1-4: Day 1 to Day 4
Characterize the PK Profile of Epetraborole and M3 in Urine: Unchanged drug excreted in urine during the time interval
Determine the fraction of unchanged drug excreted in urine during the time interval (expressed in %, calculated) for parent drug only
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3 in Urine: Renal Clearance
Determine renal clearance (Ae(0-t)/ AUC0-T) for parent drug only
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Characterize the PK Profile of Epetraborole and M3 in Dialysate: Concentration in full dialysate
Determine amount of drug measured in the whole dialysate volume during dialysis period
Time frame: Cohort 5: Day 5
Characterize the PK Profile of Epetraborole and M3 in Urine: Dialysis clearance
Determine the Dialysis clearance over the dialysis period
Time frame: Cohort 5: Day 5
Evaluate the Incidence of Treatment Emergent Adverse Events at Baseline and Through Study Completion
Incidence, relatedness, and severity of adverse events
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Evaluate Changes in Clinical Laboratory Tests from Baseline Through Study Completion
Incidence of changes in clinical laboratory measurements from baseline
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Evaluate Change in Vital Signs from Baseline Through Study Completion
Incidence of changes in blood pressure, pulse, respiratory rate, and temperature
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Evaluate Changes in 12-lead ECG Measurements from Baseline Through Study Completion
Incidence of changes in 12-lead ECG parameters from baseline
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8
Evaluate Physical Examination Abnormalities from Baseline Through Study Completion
Incidence of physical exam abnormalities
Time frame: Cohorts 1-4: Day 1 to Day 4; Cohort 5: Day 1 - Day 8