This is a Phase 1, single-center, randomized, balanced, single-dose, two-treatment, two-period, two-sequence, crossover, open-label study to evaluate the effect of food on the pharmacokinetics of PA-824. This study was designed to understand the possible effects of a high-calorie, high-fat meal on PA-824 absorption and pharmacokinetics. The hypothesis to be tested in this study is that the rate and extent of absorption of PA-824, as measured by Tmax, Cmax, AUC(0-t), and AUC(0 inf), are the same after a high-calorie, high-fat meal as compared with after a minimum 10-hour fast.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Two single administrations of 1000mg each administered by 5 tablets of 200mg, one administered in the fed state and one administered in the fasted state.
MDS Pharma Services
Lincoln, Nebraska, United States
Time of maximum drug concentration in hours [Tmax]
To compare the rate and extent of absorption as measured by Tmax of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. Tmax is obtained without interpolation.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Maximum observed drug concentration in ng/mL [Cmax]
To compare the rate and extent of absorption as measured by Cmax of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Area under the drug concentration-time curve in ng*hour/mL [AUC0-t]
To compare the rate and extent of absorption as measured by AUC0-t of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. AUC(0-t) is calculated using linear trapezoidal summation from time zero to time t, where t is the time of the last measurable concentration.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Area under the drug concentration-time curve from time zero to infinity in ng*hour/mL [AUC(0-inf)]
To compare the rate and extent of absorption as measured by AUC0-inf of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. AUC(0-inf) is calculated as AUC(0-t) + Ct/Kel.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Ratio of AUC(0-t) to AUC(0-inf) [AUC(0-t)/ AUC(0-inf)]
To compare additional pharmacokinetic (PK) parameters such as AUC(0-t)/ AUC(0-inf) of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Number of participants with adverse events
To compare the safety and tolerability as measured by the number of participants with adverse events after a single 1000-mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast.
Time frame: through the study (Day 1-Day 17)
Elimination half-life in hours [t1/2]
To compare additional pharmacokinetic (PK) parameters such as t1/2 of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. T1/2 is calculated as ln (2)/Kel.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Terminal elimination rate constant in 1/hour [Kel]
To compare additional pharmacokinetic (PK) parameters such as Kel of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. Kel is calculated by linear regression of the terminal linear portion of the log concentration vs. time curve.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Oral clearance in L/hour (Cl/F)
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To compare additional pharmacokinetic (PK) parameters such as Cl/F of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. Cl/F is calculated as dose/AUC(0-inf).
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose
Volume of distribution in L (Vd/F)
To compare additional pharmacokinetic (PK) parameters such as Vd/F of a single 1000 mg oral dose of PA-824 tablets in healthy adult male and female subjects when PA-824 is administered after a high-calorie, high-fat meal and when it is administered after a minimum 10-hour fast. Vd/F is calculated as the ratio of CL/F/Kel.
Time frame: mean through 168 hours after each dose with measurements at predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post dose