CAB is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment and prevention of human immunodeficiency virus-1 (HIV-1) infection. RIF, a rifamycin used for treatment of tuberculosis (common co-infection in HIV-infected subjects), is a known inducer of uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) and Cytochrome P450 3A4 (CYP3A4). CAB is primarily metabolized via UGT1A1 and UGT1A9, thus a drug interaction between CAB and RIF is possible. This study will be a phase I, single-center, open label, fixed-sequence cross-over study to compare the single dose PK of CAB oral 30 milligrams (mg) when co-administered with RIF 600 mg once daily at steady-state to those of CAB oral 30 mg administered alone. Fifteen subjects are planned to be enrolled to obtain 12 evaluable subjects for this study.
Study Type
INTERVENTIONAL
Allocation
NA
Masking
NONE
Enrollment
15
CAB 30 mg as 1 tablet will be administered orally with 240 mL of water in the fasted state.
RIF 600 mg as 2 capsules of 300 mg will be administered orally with 240 mL of water in the fasted state.
GSK Investigational Site
Overland Park, Kansas, United States
Plasma CAB maximum observed concentration after single dose administration (Cmax)
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
Time frame: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28
Plasma CAB area under the concentration versus time from time zero to infinity after single dose administration (AUC(0-∞))
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
Time frame: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28
Plasma CAB concentration at 24 hours post dose (C24)
Plasma PK samples collected at Period 1 24 hours post dose and at Period 3 24 hours post dose will be used to measure plasma CAB C24.
Time frame: Days 2 and 22
Plasma CAB AUC from time zero to last time point with measurable concentration after single dose administration (AUC (0-t))
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
Time frame: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28
Plasma CAB time of occurrence of Cmax (tmax) and terminal phase half-life (t1/2)
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
Time frame: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28
Plasma CAB apparent clearance following oral dosing (CL/F)
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
Time frame: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28
Number of subjects with adverse events (AEs) as a measure of safety and tolerability
AEs will be collected from the start of study treatment until the follow-up contact
Time frame: Up to 42 days
Concurrent medication as a measure of safety and tolerability
Concurrent medication will be reviewed from the start of study treatment until the follow-up contact.
Time frame: Up to 42 days
Clinical laboratory screens as a measure of safety and tolerability
Haematology, clinical chemistry, urinalysis and additional parameters will be tested.
Time frame: Day -1, 8, 13, 20, 23, 25, 28, and follow-up (up to Day 42)
Electrocardiogram (ECG) as a measure of safety and tolerability
Time frame: Day 1, 20, 21, and 23
Vital signs assessments as a measure of safety and tolerability
Time frame: Day 1, 8, 20, 21, 25, 26, 28, and follow-up (up to Day 42)
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