The purpose of this study is to test the effects of study drug (GSK1605786) on the blood levels of multiple commonly used drugs that are given to measure how your liver breaks down the study drug. These commonly-used drugs are midazolam, pioglitazone, omeprazole, and rosuvastatin which will determine the effect of GSK1605786 on how the body breaks down (metabolizes) these commonly-used drugs. Blood samples for pharmacokinetic analysis of GSK1605786, and two metabolites, \[GSK2635622 (CCX062) and GSK2656694 (CCX304)\] and four probe substrates will be collected over a 24-hour period after administration. Safety will be assessed by the measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory tests.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Subjects will receive 500 milligram (mg) (2 doses of 250 mg) GSK1605786 hard gelatin capsules twice daily orally on Days 5 to 14. GSK1605786 will be administered with 240 milliliter (mL) of water.
Subjects will receive 3 mg oral syrup of Midazolam once daily on Day 1 and Day 11. Midazolam will be administered with 240 mL of water.
Subjects will receive 15 mg tablet of pioglitazone orally once daily on Day 2 and Day 12. Pioglitazone will be administered with 240 mL of water.
Subjects will receive 40 mg hard gelatin capsules of Omeprazole once daily on Days 3 and 13. Omeprazole will be administered with 240 mL of water.
Subjects will receive 10 mg tablet of Rosuvastatin orally once daily on Days 4 and 14. Rosuvastatin will be administered with 240 mL of water.
GSK Investigational Site
Buffalo, New York, United States
To investigate the potential of GSK1605786 to inhibit or induce drug metabolism via various CYP enzymes
Midazolam AUC(0-infinity) following oral administration of midazolam alone (Day 1) and in combination with GSK1605786 (Day 11).Pioglitazone AUC(0-infinity) following oral administration of pioglitazone alone (Day 2) and in combination with GSK1605786 (Day 12).Omeprazole and 5-hydroxyomeprazole AUC(0-infinity) following oral administration of omeprazole alone (Day 3) and in combination with GSK1605786 (Day 13).
Time frame: 16 Days
To investigate the potential of GSK1605786 to inhibit the BCRP and/or OATP1B1 transporters
Rosuvastatin AUC(0-infinity) following oral administration of rosuvastatin alone (Day 4) and in combination with GSK1605786 (Day 14).
Time frame: 16 Days
To assess the safety and tolerablity of repeat oral doses of GSK1605786
Safety and tolerability during dosing with GSK1605786, alone and in combination with the various probe substrates. As assessed by adverse events, changes in vital signs, ECG, and hematology, clinical chemistry and urinalysis tests.
Time frame: 21 Days
To determine the exposure of two metabolites, GSK2635622 (CCX062) and GSK2656694 (CCX304), relative to GSK1605786 (parent compound) following single and repeat administration of GSK1605786.
Pharmacokinetic parameters \[AUC(0-infinity), AUC(0-t), AUC(0-tau), Cmax, tmax, and half-life (t1/2)\] of GSK1605786 after single and repeat administration of GSK1605786. Pharmacokinetic parameters \[AUC(0-infinity), AUC(0-t), AUC(0-tau), Cmax, tmax, and half-life (t1/2)\] of two metabolites of GSK1605786, GSK2635622 (CCX062) and GSK2656694 (CCX304) following single and repeat administration of GSK1605786.
Time frame: 16 Days
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