The purpose of this study is to investigate the potential pharmacokinetic (what the body does to the drug) interactions between multiple doses of phenytoin 200 mg every 12 hours or carbamazepine 200 mg every 12 hours and telaprevir 750 mg every 8 hours at steady-state (constant concentration of medication in the blood) in healthy participants.
This is a Phase I, open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), 2-panel, sequential treatment study. In this study 24 healthy participants will be randomly assigned equally to 2 panels. In Panel 1 the participants will receive telaprevir in Part 1 (telaprevir 750 mg every 8 hours from Day 1 to Day 9 followed by a single 750 mg dose in the morning on Day 10) and phenytoin/telaprevir in Part 2 (phenytoin 200 mg every 12 hours from Day 1 to Day 16 followed by a single 200-mg dose in the morning on Day 17; and telaprevir 750 mg every 8 hours from Day 8 to Day 16 followed by a single 750 mg dose in the morning on Day 17). In Panel 2 the participants will receive telaprevir (telaprevir 750 mg every 8 hours from Day 1 to Day 9 followed by a single 750 mg dose in the morning on Day 10) and carbamazepine/ telaprevir (carbamazepine 200 mg every 12 hours from Day 1 to Day 16 followed by a single 200-mg dose in the morning on Day 17; and telaprevir 750 mg every 8 hours from Day 8 to Day 16 followed by a single 200-mg dose in the morning on Day 17). In both panels, Part 1 and Part 2 are separated by a washout period of at least 2 weeks and maximum 4 weeks. Safety and tolerability will be assessed by evaluating adverse events, electrocardiogram, clinical laboratory examinations, vital signs and physical examination throughout the study period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Type=exact number, unit=mg, number=375, form=tablet, route=oral. Two tablets of telaprevir will be administered as per the dosing regimens for each part of both the panels.
Type=exact number, unit=mg, number=100, form=capsule, route=oral. Two capsules of phenytoin will be administered as per the dosing regimen in Part 2 of Panel 1.
Type=exact number, unit=mg, number=200, form=tablet, route=oral. One tablet of carbamazepine will be administered as per dosing regimen in Part 2 of Panel 2.
Unnamed facility
Groningen, Netherlands
Observed maximum plasma concentration (Cmax) of telaprevir.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Area under the plasma concentration time curve from time of administration up to 8 hours post dose (AUC8h) of telaprevir.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed minimum plasma concentration (Cmin) of telaprevir.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed maximum plasma concentration (Cmax) of carbamazepine.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Area under the plasma concentration time curve from time of administration up to 12 hours post dose (AUC12) of carbamazepine.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed minimum plasma concentration (Cmin) of carbamazepine.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
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Observed maximum plasma concentration (Cmax) of phenytoin.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Area under the plasma concentration time curve from time of administration up to 12 hours post dose (AUC12) of phenytoin.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Observed minimum plasma concentration (Cmin) of phenytoin.
Time frame: Part 1: predose (Day 1, 8, 9 , and 10) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, and 8h(Day 1 and Day 10); Part 2: predose (Day 1, 2, 6, 7, 8, 9, 10, 15, 16, and 17) and post dose 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 12h (Day 7, 8, and 17)
Number of participants with adverse events
Time frame: Up to Day 17
Number of participants with abnormal values of laboratory results
Time frame: Up to Day 17
Number of participants with abnormal electrocardiogram values
Time frame: Up to Day 17
Number of participants with abnormal pulse and blood pressure values
Time frame: Up to Day 17
Number of patients with abnormal physical examination findings
Time frame: Up to Day 17