A Phase I, open label, randomized, three period, one-way, two cohort, adaptive crossover study to evaluate the effect of darunavir/ritonavir plus etravirine and lopinavir/ritonavir plus etravirine on GSK1349572 pharmacokinetics in healthy adult subjects
The study is a three period, randomized, open label study. Approximately 18 healthy subjects will receive GSK1349572 50mg q24h for 5 days (Treatment A) in Period 1. Subjects will then be administered GSK1349572 50mg q24h in combination with either LPV/RTV 400/100 mg q12h and etravirine 200mg q12h (Treatment B, n=9) or DRV/RTV 600/100 mg q12h and etravirine 200mg q12h (Treatment C, n=9) for 14 days in Period 2 followed by a washout period. GSK1349572 PK data will be obtained from Periods 1 and 2 and used to inform decision making on Period 3. If GSK1349572 Cτ is reduced by more than 50% in Period 2 compared to Period 1, subjects will return to the clinic and receive GSK1349572 50mg q12h in combination with ETV and either DRV/RTV or LPV/RTV in Period 3. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug. All doses of study drugs will be taken following a moderate fat meal.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
17
Darunavir 600 mg every 12 hours for 14 days in Periods 2 and 3. Period 3 may not be done. Darunavir is approved by the FDA as an HIV medication in the protease inhibitor class.
Etravirine 200 mg every 12 hours for 14 days in Periods 2 and 3. Period 3 may not be done. Etravirine is approved by the FDA as an HIV medication in the non-nucleoside reuptake inhibitor class.
Ritonavir 100 mg every 12 hours for 14 days in Periods 2 and 3. Period 3 may not be done. Ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class.
GSK Investigational Site
Buffalo, New York, United States
Plasma GSK1349572 steady-state AUC(0-τ), Cmax, C0, Cτ, and Cmin following administration of GSK1349572 50mg and following co-administration of GSK1349572 50mg with ETV/LPV/RTV 200/400/100mg or ETV/DRV/RTV 200/600/100mg
Time frame: 14 days
Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, ECG, and vital signs assessments.
Time frame: 12 weeks
Plasma ETV PK parameters, including AUC(0-τ), Cmax, and Cmin following co-administration of GSK1349572 50mg q24h (and 50mg q12h if appropriate) and ETV/LPV/RTV 200/400/100mg q12h or ETV/DRV/RTV 200/600/100mg q12h
Time frame: 14 days
GSK1349572 PK parameters, including, tmax, tmin, CL/F and t½ following administration of GSK1349572 50mg q24h for 5 days and following co-administration of GSK1349572 50mg and ETV/LPV/RTV 200/400/100mg q12h or ETV/DRV/RTV 200/600/100mg
Time frame: 14 days
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Lopinavir 400 mg and ritonavir 100 mg every 12 hours for 14 days in Periods 2 and 3. Period 3 may not be done. Lopinavir/Ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class.
GSK1349572 50 q24h for 5 days in Period 1 and for 14 days in Period 2. GSK1349572 20 mg q12h for 14 days in Period 3 if Period 3 is done. GSK1349572 is an investigational (not approved by the FDA) HIV medication in the integrase inhibitor class.