A single-center, 4-way crossover study to evaluate the effect of single therapeutic and supratherapeutic oral doses of epetraborole on the heart rate (HR) corrected QT interval (QTc) by assessing concentration-QT (C-QT) relationship using exposure-response modeling.
On Day 1 of each period, subjects will receive 1 of 4 treatments: a single therapeutic dose of epetraborole (Treatment A), a single supratherapeutic dose of epetraborole (Treatment B), a single dose of epetraborole-matching placebo (Treatment C), or a single dose of moxifloxacin (Treatment D). Cardiodynamic ECGs and PK blood samples for epetraborole, metabolite M3, and moxifloxacin (as applicable) will be collected predose and for 24 hours postdose in each period. There will be a washout of at least 10 days between doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
24
Treatment A (Therapeutic): 500 mg epetraborole (2 x 250 mg tablets) and epetraborole matching-placebo (6 tablets)
Treatment B (Supratherapeutic): 2000 mg epetraborole (8 x 250 mg tablets)
Treatment C (Placebo control): Epetraborole matching-placebo (8 tablets)
423001
Tempe, Arizona, United States
Changes to QTc interval
Effect of epetraborole plasma concentrations on the QTc interval using linear mixed effect exposure-response modeling, including the predicted ddQTc at Cmax values corresponding to exposure levels of interest.
Time frame: Study Day -1 to Study Day 2
Effect of epetraborole plasma concentrations on other ECG parameters on QTc
Measure the Effect of epetraborole plasma concentrations on other ECG parameters on QTc
Time frame: Study Day -1 to Study Day 2
Assay sensitivity
Assay sensitivity assessment with ddQTc at the geometric mean Cmax value predicted from a linear mixed effect model evaluating the relationship between QTc and moxifloxacin plasma concentrations (exposure-response modeling).
Time frame: Study Day -1 to Study Day 2
Analysis of dQTc
QTc interval using a mixed effect analysis of covariance (ANCOVA) carried out as appropriate to analyze dQTc at each time point post baseline.
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of AUC0 t
Analysis of PK Concentration for epetraborole and metabolite M3 of AUC0 t
Time frame: Study Day -1 to Study Day 2
Evaluation of TEAEs
TEAEs
Time frame: Study Day 1 through Study Day 14
Safety Vital Signs changes of body temperature
Measure Safety Vital Signs changes of body temperature
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Treatment D (Positive control): 400 mg moxifloxacin (1 x 400 mg tablet)
Time frame: Study Day 1 through Study Day 14
Orthostatic Vital Signs changes of Heart Rate from supine to standing position.
Measure Orthostatic Vital Signs changes of Heart Rate from supine to standing position.
Time frame: Study Day 1 through Study Day 14
Effect of epetraborole plasma concentrations on other ECG parameters on, PR
Measure the Effect of epetraborole plasma concentrations on other ECG parameters on, PR
Time frame: Study Day -1 to Study Day 2
Effect of epetraborole plasma concentrations on other ECG parameters on QRS duration
Measure the Effect of epetraborole plasma concentrations on other ECG parameters on QRS duration.
Time frame: Study Day -1 to Study Day 2
Effect of epetraborole plasma concentrations on other ECG parameters on HR.
Measure the Effect of epetraborole plasma concentrations on other ECG parameters on HR.
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of AUC0 inf
Analysis of PK Concentration for epetraborole and metabolite M3 of AUC0 inf
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of AUC%extrap
Analysis of PK Concentration for epetraborole and metabolite M3 of AUC%extrap
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of Cmax
Analysis of PK Concentration for epetraborole and metabolite M3 of Cmax
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of Tmax
Analysis of PK Concentration for epetraborole and metabolite M3 of Tmax
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of Kel
Analysis of PK Concentration for epetraborole and metabolite M3 of Kel
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of t½
Analysis of PK Concentration for epetraborole and metabolite M3 of t½
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of CL/F (parent only),
Analysis of PK Concentration for epetraborole and metabolite M3 of CL/F (parent only),
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of Vz/F (parent only)
Analysis of PK Concentration for epetraborole and metabolite M3 of Vz/F (parent only
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of MR AUC0 t
Analysis of PK Concentration for epetraborole and metabolite M3 of MR AUC0 t
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of MR AUC0 inf
Analysis of PK Concentration for epetraborole and metabolite M3 of MR AUC0 inf
Time frame: Study Day -1 to Study Day 2
PK Concentration analysis for epetraborole and metabolite M3 of MR Cmax
Analysis of PK Concentration for epetraborole and metabolite M3 of MR Cmax
Time frame: Study Day -1 to Study Day 2
Safety Vital Signs changes of respiratory rate
Measure Safety Vital Signs changes of respiratory rate
Time frame: Study Day 1 through Study Day 14
Safety Vital Signs changes of blood pressure
Measure Safety Vital Signs changes of blood pressure (systolic and diastolic)
Time frame: Study Day 1 through Study Day 14
Safety Vital Signs changes of heart rate
measure Safety Vital Signs changes of heart rate
Time frame: Study Day 1 through Study Day 14
Orthostatic Vital Signs changes of blood pressure from supine to standing position.
Measure Orthostatic Vital Signs changes of blood pressure from supine to standing position (systolic and diastolic).
Time frame: Study Day 1 through Study Day 14