Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Epetraborole · 3 trials · 3 indications
Improvement in severity of at least 50% of the symptoms present at baseline and no deterioration in severity of symptoms present at baseline
Defined as 3 consecutive negative cultures one month apart without intervening or subsequent positives
Defined as improvement in sputum colony count category as defined by Griffith et al, 2015
QOL-B Domain scores range from 0 to 100, with higher scores indicating better health-related quality of life
MACrO2 scores range from 0 to 100, with lower scores indicating better symptom-related quality of life
Defined as 2 consecutive negative cultures collected one month apart without intervening or subsequent positives
Determination of the maximum observed plasma concentration (Cmax)
Determine the area under the plasma concentration versus time curve from time 0 to the last time point evaluated (AUC0-t)
Determine the area under the plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)
Determine area under the drug concentration versus time curve, from time zero to infinity (AUC0-∞)
Determine the apparent total plasma clearance of drug (CL/F)
Determination the time to maximum plasma concentration (Tmax)
Determine the AUC from 0 to the last quantifiable concentration AUClast immediately after the end of dialysis period from inflow (arterial) line
Determine the AUC from 0 to the last quantifiable concentration AUClast immediately after the end of dialysis period from inflow (venous) line
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)
Determine the fraction of unchanged drug excreted in urine during the time interval (expressed in %, calculated) for parent drug only
Determine renal clearance (Ae(0-t)/ AUC0-T) for parent drug only
Determine amount of drug measured in the whole dialysate volume during dialysis period
Determine the Dialysis clearance over the dialysis period
Incidence, relatedness, and severity of adverse events
Incidence of changes in clinical laboratory measurements from baseline
Incidence of changes in blood pressure, pulse, respiratory rate, and temperature
Incidence of changes in 12-lead ECG parameters from baseline
Incidence of physical exam abnormalities
Determination of the maximum plasma concentration (Cmax)
Determination of the minimum steady state plasma drug concentration during a dosage interval (Cmin)
Determination the time to maximum plasma concentration (Tmax)
Determine the area under the plasma concentration versus time curve from time 0 to the last time point evaluated (AUC0-t) with the plasma concentration at time "t" being the last measurable concentration
Determine area under the drug concentration versus time curve, from time zero to infinity (AUC0-inf)
Determine the actual time of last quantifiable concentration used in the determination of AUC0-last (Tlast)
Determine the apparent terminal half-life (t½)
Determine apparent terminal elimination rate constant (Kel)
| Arm | Type | Description |
|---|---|---|
| High Dose Epetraborole | EXPERIMENTAL | This arm is a daily treatment regimen of a 750mg oral dose of Epetraborole. |
| Low Dose Epetraborole | EXPERIMENTAL | This arm is a daily treatment regimen of a 500mg oral dose of Epetraborole. |
| High Dose Placebo | PLACEBO_COMPARATOR | This arm is a daily treatment regimen of a placebo, matching the high dose experimental arm. |
| Low Dose Placebo | PLACEBO_COMPARATOR | This arm is a daily treatment regimen of a placebo, matching the low dose experimental arm. |
| Open Label | EXPERIMENTAL | All subjects in Cohorts 1-4 receive 500 mg epetraborole once; Subjects on Cohort 5 receive 500 mg epetraborole twice |
| Epetraborole for Dose Ranging | EXPERIMENTAL | Epetraborole hydrochloride 250 mg, 500 mg, 750 mg, or 1000 mg PO q24h or 500 mg or 1000 mg PO q48h |
| Placebo for Dose Ranging | PLACEBO_COMPARATOR | Matching placebo for dose ranging |
| Epetraborole for Food Effect | EXPERIMENTAL | Food effect cohort, single dose in fed and fasted conditions, dosage to be determined based on pharmacokinetics data obtained from previous cohorts |
| Placebo for Food Effect | PLACEBO_COMPARATOR | Food effect cohort, single dose in fed and fasted conditions, dosage to be determined based on pharmacokinetics data obtained from previous cohorts |
| Name | Type | Description |
|---|---|---|
| Epetraborole | DRUG | High-dose intervention (750mg daily) |
| Placebo | DRUG | Placebo intervention (matching the high-dose experimental intervention) |
Inclusion Criteria: 1. Male or female patients who are 18 years of age or older. 2. Willing and able to provide written informed consent. 3. Patients with MABc lung disease, meeting the following (a) Microbiological, (b) Clinical, (c) Radiographic a. Microbiological criteria: i. Documentation o...